Publications

@article{robinson_consequences_2018,

title = {Consequences of VHL Loss on Global DNA Methylome},

author = {Claire M Robinson and Francois Lefebvre and Betty P Poon and Aurelie Bousard and Xiaojun Fan and Mark Lathrop and Jorg Tost and William Y Kim and Yasser Riazalhosseini and Michael Ohh},

url = {https://www.nature.com/articles/s41598-018-21524-5},

doi = {10.1038/s41598-018-21524-5},

issn = {2045-2322},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Scientific Reports},

volume = {8},

number = {1},

pages = {3313},

abstract = {In clear-cell renal cell carcinoma (ccRCC), loss of von Hippel-Lindau (VHL) tumour suppressor gene and reduced oxygen tension promote stabilisation of hypoxia-inducible factor (HIF) family of transcription factors, which promote changes in the expression of genes that contribute to oncogenesis. Multiple studies have demonstrated significant perturbations in DNA methylation in ccRCC via largely unclear mechanisms that modify the transcriptional output of tumour cells. Here, we show that the methylation status of the CpG dinucleotide within the consensus hypoxia-responsive element (HRE) markedly influences the binding of HIF and that the loss of VHL results in significant alterations in the DNA methylome. Surprisingly, hypoxia, which likewise promotes HIF stabilisation and activation, has relatively few effects on global DNA methylation. Gene expression analysis of ccRCC patient samples highlighted expression of a group of genes whose transcription correlated with methylation changes, including hypoxic responsive genes such as VEGF and TGF. These results suggest that the loss of VHL alters DNA methylation profile across the genome, commonly associated with and contributing to ccRCC progression.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{kou_response_2018,

title = {The Response of a 16S Ribosomal RNA Gene Fragment Amplified Community to Lead, Zinc, and Copper Pollution in a Shanghai Field Trial},

author = {Shumeng Kou and Gilles Vincent and Emmanuel Gonzalez and Frederic E Pitre and Michel Labrecque and Nicholas J B Brereton},

url = {https://www.frontiersin.org/articles/10.3389/fmicb.2018.00366/full},

doi = {10.3389/fmicb.2018.00366},

issn = {1664-302X},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Frontiers in Microbiology},

volume = {9},

abstract = {Industrial and agricultural activities have caused extensive metal contamination of land throughout China and across the globe. The pervasive nature of metal pollution can be harmful to human health and can potentially cause substantial negative impact to the biosphere. To investigate the impact of anthropogenic metal pollution found in high concentrations in industrial, agricultural and urban environments, 16S ribosomal RNA gene amplicon sequencing was used to track change in the amplified microbial community after metal contamination in a large-scale field experiment in Shanghai. 1,566 operational taxonomic units (OTUs) identified from 448,108 sequences gathered from 20 plots treated as controls or with lead, zinc, copper or all three metals. Constrained Analysis of Principal Coordinates ordination did not separate control and lead treatment but could separate control/lead, zinc, copper and three metal treatment. DESeq2 was applied to identify 93 significantly differentially abundant OTUs varing in 211 pairwise instances between the treatments. Differentially abundant OTUs representing genera or species belonging to the phyla Chloroflexi, Cyanobacteria, Firmicutes, Latescibacteria and Planctomycetes were almost universally reduced in abundance due to zinc, copper or three metal treatment; with three metal treatment abolishing the detection of some OTUs, such as Leptolyngbya, Desmonostoc muscorum and Microcoleus steenstrupii. The greatest increases due to metal treatment were observed in Bacteroidetes, Actinobacteria, Chlamydiae, Nitrospirae and Proteobacteria (α, β, ƍ and γ); the most (relative) abundant being uncharacterised species within the genera Methylobacillus, Solirubrobacter and Ohtaekwangia. Three metal treatment alone resulted in identification of 22 OTUs (genera or species) which were not detected in control soil, notably including Yonghaparkia alkaliphila, Pedobacter steynii, Pseudolabrys taiwanensis, Methylophilus methylotrophus, Nitrosospira, and Lysobacter mobilis. The capacity to track alterations of an amplified microbial community at high taxonomic resolution using modern bioinformatic approaches, as well as identifying where that resolution is lost for technical or biological reasons, provides an insight into the complexity of the microbial world resisting anthropogenic pollution. While functional assessment of uncharacterised organisms within environmental samples is technically challenging, an important step is observing those organisms able to tolerate extreme stress and to recognise the extent to which important amplifiable community members still require characterisation.},

note = {Publisher: Frontiers},

keywords = {16S rRNA, bioremediation, Heavy metal contamination, Metagenomics, soil bacteria},

pubstate = {published},

tppubtype = {article}

}

@article{kanagaratham_loss_2018,

title = {Loss of the zona pellucida-binding protein 2 (Zpbp2) gene in mice impacts airway hypersensitivity and lung lipid metabolism in a sex-dependent fashion},

author = {Cynthia Kanagaratham and Victoria Chiwara and Bianca Ho and Sanny Moussette and Mina Youssef and David Venuto and Lucie Jeannotte and Guillaume Bourque and Juan Bautista de Sanctis and Danuta Radzioch and Anna K Naumova},

url = {https://doi.org/10.1007/s00335-018-9743-x},

doi = {10.1007/s00335-018-9743-x},

issn = {1432-1777},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Mammalian Genome},

volume = {29},

number = {3},

pages = {281--298},

abstract = {The human chromosomal region 17q12–q21 is one of the best replicated genome-wide association study loci for childhood asthma. The associated SNPs span a large genomic interval that includes several protein-coding genes. Here, we tested the hypothesis that the zona pellucida-binding protein 2 (ZPBP2) gene residing in this region contributes to asthma pathogenesis using a mouse model. We tested the lung phenotypes of knock-out (KO) mice that carry a deletion of the Zpbp2 gene. The deletion attenuated airway hypersensitivity (AHR) in female, but not male, mice in the absence of allergic sensitization. Analysis of the lipid profiles of their lungs showed that female, but not male, KO mice had significantly lower levels of sphingosine-1-phosphate (S1P), very long-chain ceramides (VLCCs), and higher levels of long-chain ceramides compared to wild-type controls. Furthermore, in females, lung resistance following methacholine challenge correlated with lung S1P levels (Pearson correlation coefficient 0.57) suggesting a link between reduced AHR in KO females, Zpbp2 deletion, and S1P level regulation. In livers, spleens and blood plasma, however, VLCC, S1P, and sphingosine levels were reduced in both KO females and males. We also find that the Zpbp2 deletion was associated with gain of methylation in the adjacent DNA regions. Thus, we demonstrate that the mouse ortholog of ZPBP2 has a role in controlling AHR in female mice. Our data also suggest that Zpbp2 may act through regulation of ceramide metabolism. These findings highlight the importance of phospholipid metabolism for sexual dimorphism in AHR.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{rains_reconstructing_2018,

title = {Reconstructing the suberin pathway in poplar by chemical and transcriptomic analysis of bark tissues},

author = {Meghan K Rains and Nayana Dilini Gardiyehewa de Silva and Isabel Molina},

url = {https://doi.org/10.1093/treephys/tpx060},

doi = {10.1093/treephys/tpx060},

issn = {1758-4469},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Tree Physiology},

volume = {38},

number = {3},

pages = {340--361},

abstract = {The tree bark periderm confers the first line of protection against pathogen invasion and abiotic stresses. The phellogen (cork cambium) externally produces cork (phellem) cells that are dead at maturity; while metabolically active, these tissues synthesize cell walls, as well as cell wall modifications, namely suberin and waxes. Suberin is a heteropolymer with aliphatic and aromatic domains, composed of acylglycerols, cross-linked polyphenolics and solvent-extractable waxes. Although suberin is essentially ubiquitous in vascular plants, the biochemical functions of many enzymes and the genetic regulation of its synthesis are poorly understood. We have studied suberin and wax composition in four developmental stages of hybrid poplar (Populus tremula x Populus alba) stem periderm. The amounts of extracellular ester-linked acyl lipids per unit area increased with tissue age, a trend not observed with waxes. We used RNA-Seq deep-sequencing technology to investigate the cork transcriptome at two developmental stages. The transcript analysis yielded 455 candidates for the biosynthesis and regulation of poplar suberin, including genes with proven functions in suberin metabolism, genes highlighted as candidates in other plant species and novel candidates. Among these, a gene encoding a putative lipase/acyltransferase of the GDSL-motif family emerged as a suberin polyester synthase candidate, and specific isoforms of peroxidase and laccase genes were preferentially expressed in cork, suggesting that their corresponding proteins may be involved in cross-linking aromatics to form lignin-like polyphenolics. Many transcriptional regulators with possible roles in meristem identity, cork differentiation and acyl-lipid metabolism were also identified. Our work provides the first large-scale transcriptomic dataset on the suberin-synthesizing tissue of poplar bark, contributing to our understanding of tree bark development at the molecular level. Based on these data, we have proposed a number of hypotheses that can be used in future research leading to novel biological insights into suberin biosynthesis and its physiological function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{gonzalez_trees_2018,

title = {Trees, fungi and bacteria: tripartite metatranscriptomics of a root microbiome responding to soil contamination},

author = {E Gonzalez and F E Pitre and A P Pagé and J Marleau and W Guidi Nissim and M St-Arnaud and M Labrecque and S Joly and E Yergeau and N J B Brereton},

url = {https://doi.org/10.1186/s40168-018-0432-5},

doi = {10.1186/s40168-018-0432-5},

issn = {2049-2618},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Microbiome},

volume = {6},

number = {1},

pages = {53},

abstract = {One method for rejuvenating land polluted with anthropogenic contaminants is through phytoremediation, the reclamation of land through the cultivation of specific crops. The capacity for phytoremediation crops, such as Salix spp., to tolerate and even flourish in contaminated soils relies on a highly complex and predominantly cryptic interacting community of microbial life.},

keywords = {Metatranscriptomics, Microbiome, Phytoremediation, Rhizosphere, Salix},

pubstate = {published},

tppubtype = {article}

}

@article{monlong_global_2018,

title = {Global characterization of copy number variants in epilepsy patients from whole genome sequencing},

author = {Jean Monlong and Simon L Girard and Caroline Meloche and Maxime Cadieux-Dion and Danielle M Andrade and Ron G Lafreniere and Micheline Gravel and Dan Spiegelman and Alexandre Dionne-Laporte and Cyrus Boelman and Fadi F Hamdan and Jacques L Michaud and Guy Rouleau and Berge A Minassian and Guillaume Bourque and Patrick Cossette},

url = {https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007285},

doi = {10.1371/journal.pgen.1007285},

issn = {1553-7404},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {PLOS Genetics},

volume = {14},

number = {4},

pages = {e1007285},

abstract = {Epilepsy will affect nearly 3% of people at some point during their lifetime. Previous copy number variants (CNVs) studies of epilepsy have used array-based technology and were restricted to the detection of large or exonic events. In contrast, whole-genome sequencing (WGS) has the potential to more comprehensively profile CNVs but existing analytic methods suffer from limited accuracy. We show that this is in part due to the non-uniformity of read coverage, even after intra-sample normalization. To improve on this, we developed PopSV, an algorithm that uses multiple samples to control for technical variation and enables the robust detection of CNVs. Using WGS and PopSV, we performed a comprehensive characterization of CNVs in 198 individuals affected with epilepsy and 301 controls. For both large and small variants, we found an enrichment of rare exonic events in epilepsy patients, especially in genes with predicted loss-of-function intolerance. Notably, this genome-wide survey also revealed an enrichment of rare non-coding CNVs near previously known epilepsy genes. This enrichment was strongest for non-coding CNVs located within 100 Kbp of an epilepsy gene and in regions associated with changes in the gene expression, such as expression QTLs or DNase I hypersensitive sites. Finally, we report on 21 potentially damaging events that could be associated with known or new candidate epilepsy genes. Our results suggest that comprehensive sequence-based profiling of CNVs could help explain a larger fraction of epilepsy cases.},

note = {Publisher: Public Library of Science},

keywords = {Catalogs, Epilepsy, Eyelids, Genetic linkage, Genetic polymorphism, genomics, Monozygotic twins, Twins},

pubstate = {published},

tppubtype = {article}

}

@article{singh_effects_2018,

title = {Effects of developmental lead exposure on the hippocampal methylome: Influences of sex and timing and level of exposure},

author = {G Singh and V Singh and Zi-Xuan Wang and G Voisin and F Lefebvre and J-M Navenot and B Evans and M Verma and D W Anderson and J S Schneider},

url = {https://www.sciencedirect.com/science/article/pii/S0378427418301085},

doi = {10.1016/j.toxlet.2018.03.021},

issn = {0378-4274},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Toxicology Letters},

volume = {290},

pages = {63--72},

abstract = {Developmental lead (Pb) exposure results in persistent cognitive/behavioral impairments as well as an elevated risk for developing a variety of diseases in later life. Environmental exposures during development can result in a variety of epigenetic changes, including alterations in DNA methylation, that can influence gene expression patterns and affect the function and development of the nervous system. The present promoter-based methylation microarray profiling study explored the extent to which developmental Pb exposure may modify the methylome of a brain region, hippocampus, known to be sensitive to the effects of Pb exposure. Male and female Long Evans rats were exposed to 0 ppm, 150 ppm, 375 ppm, or 750 ppm Pb through perinatal exposures (gestation through lactation), early postnatal exposures (birth through weaning), or long-term postnatal exposures (birth through postnatal day 55). Results showed a significant contribution of sex to the hippocampal methylome and effects of Pb exposure level, with non-linear dose response effects on methylation. Surprisingly, the developmental period of exposure contributed only a small amount of variance to the overall data and gene ontology (GO) analysis revealed the largest number of overrepresented GO terms in the groups with the lowest level of exposure. The highest number of significant differentially methylated regions was found in females exposed to Pb at the lowest exposure level. Our data reinforce the significant effect that low level Pb exposure may have on gene-specific DNA methylation patterns in brain and that this occurs in a sex-dependent manner.},

keywords = {Brain, Developmental exposure, DNA methylation, epigenetics, Heavy metal, Hippocampus, Lead toxicity, Sex},

pubstate = {published},

tppubtype = {article}

}

@article{hirukawa_targeting_2018,

title = {Targeting EZH2 reactivates a breast cancer subtype-specific anti-metastatic transcriptional program},

author = {Alison Hirukawa and Harvey W Smith and Dongmei Zuo and Catherine R Dufour and Paul Savage and Nicholas Bertos and Radia M Johnson and Tung Bui and Guillaume Bourque and Mark Basik and Vincent Giguère and Morag Park and William J Muller},

url = {https://www.nature.com/articles/s41467-018-04864-8},

doi = {10.1038/s41467-018-04864-8},

issn = {2041-1723},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Nature Communications},

volume = {9},

number = {1},

pages = {2547},

abstract = {Emerging evidence has illustrated the importance of epigenomic reprogramming in cancer, with altered post-translational modifications of histones contributing to pathogenesis. However, the contributions of histone modifiers to breast cancer progression are unclear, and how these processes vary between molecular subtypes has yet to be adequately addressed. Here we report that genetic or pharmacological targeting of the epigenetic modifier Ezh2 dramatically hinders metastatic behaviour in both a mouse model of breast cancer and patient-derived xenografts reflective of the Luminal B subtype. We further define a subtype-specific molecular mechanism whereby EZH2 maintains H3K27me3-mediated repression of the FOXC1 gene, thereby inactivating a FOXC1-driven, anti-invasive transcriptional program. We demonstrate that higher FOXC1 is predictive of favourable outcome specifically in Luminal B breast cancer patients and establish the use of EZH2 methyltransferase inhibitors as a viable strategy to block metastasis in Luminal B breast cancer, where options for targeted therapy are limited.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{chong_metaboanalyst_2018,

title = {MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis},

author = {Jasmine Chong and Othman Soufan and Carin Li and Iurie Caraus and Shuzhao Li and Guillaume Bourque and David S Wishart and Jianguo Xia},

url = {https://doi.org/10.1093/nar/gky310},

doi = {10.1093/nar/gky310},

issn = {0305-1048},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Nucleic Acids Research},

volume = {46},

number = {W1},

pages = {W486--W494},

abstract = {We present a new update to MetaboAnalyst (version 4.0) for comprehensive metabolomic data analysis, interpretation, and integration with other omics data. Since the last major update in 2015, MetaboAnalyst has continued to evolve based on user feedback and technological advancements in the field. For this year's update, four new key features have been added to MetaboAnalyst 4.0, including: (1) real-time R command tracking and display coupled with the release of a companion MetaboAnalystR package; (2) a MS Peaks to Pathways module for prediction of pathway activity from untargeted mass spectral data using the mummichog algorithm; (3) a Biomarker Meta-analysis module for robust biomarker identification through the combination of multiple metabolomic datasets and (4) a Network Explorer module for integrative analysis of metabolomics, metagenomics, and/or transcriptomics data. The user interface of MetaboAnalyst 4.0 has been reengineered to provide a more modern look and feel, as well as to give more space and flexibility to introduce new functions. The underlying knowledgebases (compound libraries, metabolite sets, and metabolic pathways) have also been updated based on the latest data from the Human Metabolome Database (HMDB). A Docker image of MetaboAnalyst is also available to facilitate download and local installation of MetaboAnalyst. MetaboAnalyst 4.0 is freely available at http://metaboanalyst.ca.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{monlong_human_2018,

title = {Human copy number variants are enriched in regions of low mappability},

author = {Jean Monlong and Patrick Cossette and Caroline Meloche and Guy Rouleau and Simon L Girard and Guillaume Bourque},

url = {https://doi.org/10.1093/nar/gky538},

doi = {10.1093/nar/gky538},

issn = {0305-1048},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Nucleic Acids Research},

volume = {46},

number = {14},

pages = {7236--7249},

abstract = {Copy number variants (CNVs) are known to affect a large portion of the human genome and have been implicated in many diseases. Although whole-genome sequencing (WGS) can help identify CNVs, most analytical methods suffer from limited sensitivity and specificity, especially in regions of low mappability. To address this, we use PopSV, a CNV caller that relies on multiple samples to control for technical variation. We demonstrate that our calls are stable across different types of repeat-rich regions and validate the accuracy of our predictions using orthogonal approaches. Applying PopSV to 640 human genomes, we find that low-mappability regions are approximately 5 times more likely to harbor germline CNVs, in stark contrast to the nearly uniform distribution observed for somatic CNVs in 95 cancer genomes. In addition to known enrichments in segmental duplication and near centromeres and telomeres, we also report that CNVs are enriched in specific types of satellite and in some of the most recent families of transposable elements. Finally, using this comprehensive approach, we identify 3455 regions with recurrent CNVs that were missing from existing catalogs. In particular, we identify 347 genes with a novel exonic CNV in low-mappability regions, including 29 genes previously associated with disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{bourque_comparing_2018,

title = {Comparing Apples to Apples and Oranges to Oranges},

author = {Guillaume Bourque},

url = {https://www.cell.com/trends/genetics/abstract/S0168-9525(18)30087-8},

doi = {10.1016/j.tig.2018.05.002},

issn = {0168-9525},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Trends in Genetics},

volume = {34},

number = {8},

pages = {571--572},

note = {Publisher: Elsevier},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{brochu_topoisomerases_2018,

title = {Topoisomerases I and III inhibit R-loop formation to prevent unregulated replication in the chromosomal Ter region of Escherichia coli},

author = {Julien Brochu and Émilie Vlachos-Breton and Sarah Sutherland and Makisha Martel and Marc Drolet},

url = {https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007668},

doi = {10.1371/journal.pgen.1007668},

issn = {1553-7404},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {PLOS Genetics},

volume = {14},

number = {9},

pages = {e1007668},

abstract = {Type 1A topoisomerases (topos) are the only ubiquitous topos. E. coli has two type 1A topos, topo I (topA) and topo III (topB). Topo I relaxes negative supercoiling in part to inhibit R-loop formation. To grow, topA mutants acquire compensatory mutations, base substitutions in gyrA or gyrB (gyrase) or amplifications of a DNA region including parC and parE (topo IV). topB mutants grow normally and topo III binds tightly to single-stranded DNA. What functions topo I and III share in vivo and how cells lacking these important enzymes can survive is unclear. Previously, a gyrB(Ts) compensatory mutation was used to construct topA topB null mutants. These mutants form very long filaments and accumulate diffuse DNA, phenotypes that appears to be related to replication from R-loops. Here, next generation sequencing and qPCR for marker frequency analysis were used to further define the functions of type 1A topos. The results reveal the presence of a RNase HI-sensitive origin of replication in the terminus (Ter) region of the chromosome that is more active in topA topB cells than in topA and rnhA (RNase HI) null cells. The S9.6 antibodies specific to DNA:RNA hybrids were used in dot-blot experiments to show the accumulation of R-loops in rnhA, topA and topA topB null cells. Moreover topA topB gyrB(Ts) strains, but not a topA gyrB(Ts) strain, were found to carry a parC parE amplification. When a topA gyrB(Ts) mutant carried a plasmid producing topo IV, topB null transductants did not have parC parE amplifications. Altogether, the data indicate that in E. coli type 1A topos are required to inhibit R-loop formation/accumulation mostly to prevent unregulated replication in Ter, and that they are essential to prevent excess negative supercoiling and its detrimental effects on cell growth and survival.},

note = {Publisher: Public Library of Science},

keywords = {DNA amplification, DNA extraction, DNA replication, genomics, K cells, Next-generation sequencing, Phenotypes, Ribonucleases},

pubstate = {published},

tppubtype = {article}

}

@article{defo_rna-sequencing_2018,

title = {RNA-sequencing to assess the health of wild yellow perch (Perca flavescens) populations from the St. Lawrence River, Canada},

author = {Michel A Defo and Mélanie Douville and Maeva Giraudo and Philippe Brodeur and Monique Boily and Magali Houde},

url = {https://www.sciencedirect.com/science/article/pii/S0269749118317299},

doi = {10.1016/j.envpol.2018.09.133},

issn = {0269-7491},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Environmental Pollution},

volume = {243},

pages = {1657--1668},

abstract = {This study aimed to better understand in situ cumulative effects of anthropogenic stressors on the health of St. Lawrence River (QC, Canada) yellow perch populations using high-throughput transcriptomics and a multi-biological level approach. Fish were collected in the upstream fluvial Lake Saint-François (LSF) with low degree of environmental perturbations; Lake Saint-Louis (LSL) considered having a moderate degree of anthropogenic stressors, and Lake Saint-Pierre (LSP) a sector where the perch population has been severely declining. Morphometric results indicated that fish from the downstream LSP showed lower body condition compared to LSF and LSL. Liver transcriptomic responses were assessed by RNA-sequencing. Two hundred and eighty genes were over-transcribed in LSP perch while 200 genes were under-transcribed compared to LSF and LSL. In LSP fish, genes transcripts related to reproduction, retinol, iron, thyroid hormones, oxidative stress, lipid metabolism and immune functions were among the most abundant suggesting that multiple metabolic and physiological pathways were impacted by environmental stressors at this site. Inhibition of liver superoxide dismutase, catalase and glutathione S-transferase activities were also observed at the cellular level. Overall, identified impacted biological pathways in perch from LSP may help understand the precarious state of this population and identify the factors inhibiting its recovery.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{rehan_conserved_2018,

title = {Conserved Genes Underlie Phenotypic Plasticity in an Incipiently Social Bee},

author = {Sandra M Rehan and Karl M Glastad and Michael A Steffen and Cameron R Fay and Brendan G Hunt and Amy L Toth},

url = {https://doi.org/10.1093/gbe/evy212},

doi = {10.1093/gbe/evy212},

issn = {1759-6653},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Genome Biology and Evolution},

volume = {10},

number = {10},

pages = {2749--2758},

abstract = {Despite a strong history of theoretical work on the mechanisms of social evolution, relatively little is known of the molecular genetic changes that accompany transitions from solitary to eusocial forms. Here, we provide the first genome of an incipiently social bee that shows both solitary and social colony organization in sympatry, the Australian carpenter bee Ceratina australensis. Through comparative analysis, we provide support for the role of conserved genes and cis-regulation of gene expression in the phenotypic plasticity observed in nest-sharing, a rudimentary form of sociality. Additionally, we find that these conserved genes are associated with caste differences in advanced eusocial species, suggesting these types of mechanisms could pave the molecular pathway from solitary to eusocial living. Genes associated with social nesting in this species show signatures of being deeply conserved, in contrast to previous studies in other bees showing novel and faster-evolving genes are associated with derived sociality. Our data provide support for the idea that the earliest social transitions are driven by changes in gene regulation of deeply conserved genes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{itcus_bacterial_2018,

title = {Bacterial and archaeal community structures in perennial cave ice},

author = {Corina Itcus and Madalina D Pascu and Paris Lavin and Aurel Perşoiu and Lavinia Iancu and Cristina Purcarea},

url = {https://www.nature.com/articles/s41598-018-34106-2},

doi = {10.1038/s41598-018-34106-2},

issn = {2045-2322},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Scientific Reports},

volume = {8},

number = {1},

pages = {15671},

abstract = {Ice entrenched microcosm represents a vast reservoir of novel species and a proxy for past climate reconstitution. Among glacial ecosystems, ice caves represent one of the scarcely investigated frozen habitats. To characterize the microbial diversity of perennial ice from karst ecosystems, Roche 454 sequencing of 16S rRNA gene amplicons from the underground ice block of Scarisoara Ice Cave (Romania) was applied. The temporal distribution of bacterial and archaeal community structures from newly formed, 400, and 900 years old ice layers was surveyed and analyzed in relation with the age and geochemical composition of the ice substrate. The microbial content of cave ice layers varied from 3.3 104 up to 7.5 105 cells mL−1, with 59–78% viability. Pyrosequencing generated 273,102 reads for the five triplicate ice samples, which corresponded to 3,464 operational taxonomic units (OTUs). The distribution of the bacterial phyla in the perennial cave ice varied with age, organic content, and light exposure. Proteobacteria dominated the 1 and 900 years old organic rich ice deposits, while Actinobacteria was mostly found in 900 years old ice strata, and Firmicutes was best represented in 400 years old ice. Cyanobacteria and Chlorobi representatives were identified mainly from the ice block surface samples exposed to sunlight. Archaea was observed only in older ice strata, with a high incidence of Crenarchaeota and Thaumarchaeaota in the 400 years old ice, while Euryarchaeota dominated the 900 years old ice layers, with Methanomicrobia representing the predominant taxa. A large percentage (55.7%) of 16S rRNA gene amplicons corresponded to unidentified OTUs at genus or higher taxa levels, suggesting a greater undiscovered bacterial diversity in this glacial underground habitat. The prokaryotes distribution across the cave ice block revealed the presence of 99 phylotypes specific for different ice layers, in addition to the shared microbial community. Ice geochemistry represented an important factor that explained the microbial taxa distribution in the cave ice block, while the total organic carbon content had a direct impact on the cell density of the ice microcosm. Both bacterial and archaeal community structures appeared to be affected by climate variations during the ice formation, highlighting the cave ice microbiome as a source of putative paleoclimatic biomarkers. This report constitutes the first high-throughput sequencing study of the cave ice microbiome and its distribution across the perennial underground glacier of an alpine ice cave.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lewin_gene_2018,

title = {Gene expression signatures prognostic for relapse in stage I testicular germ cell tumours},

author = {Jeremy Lewin and Laleh Soltan Ghoraie and Philippe L Bedard and Robert J Hamilton and Peter Chung and Malcolm Moore and Michael A S Jewett and Lynn Anson‐Cartwright and Carl Virtanen and Neil Winegarden and Julie Tsao and Padraig Warde and Joan Sweet and Benjamin Haibe‐Kains and Aaron R Hansen},

url = {https://bjui-journals.onlinelibrary.wiley.com/doi/abs/10.1111/bju.14372},

doi = {https://doi.org/10.1111/bju.14372},

issn = {1464-410X},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {BJU International},

volume = {122},

number = {5},

pages = {814--822},

abstract = {Objectives To identify differentially expressed genes between relapsed and non-relapsed clinical stage I testicular germ cell tumours (TGCTs). Materials and Methods We reviewed patients with clinical stage I non-seminoma and seminoma from an institutional database (2000–2012) who were managed by active surveillance. Patients with non-relapsed non-seminoma and non-relapsed seminoma were defined as being relapse-free after 2 and 3 years of surveillance, respectively. RNA extraction and gene expression analysis was performed on archival primary tumour samples and gene-set enrichment analysis (GSEA) was conducted in order to identify differentiating biological pathways. Results A total of 57 patients (relapsed non-seminoma},

note = {_eprint: https://bjui-journals.onlinelibrary.wiley.com/doi/pdf/10.1111/bju.14372},

keywords = {#TesticularCancer, #tscsm, Gene expression, germ cell tumour, relapse, surveillance, testicular neoplasm},

pubstate = {published},

tppubtype = {article}

}

@article{bourque_ten_2018,

title = {Ten things you should know about transposable elements},

author = {Guillaume Bourque and Kathleen H Burns and Mary Gehring and Vera Gorbunova and Andrei Seluanov and Molly Hammell and Michaël Imbeault and Zsuzsanna Izsvák and Henry L Levin and Todd S Macfarlan and Dixie L Mager and Cédric Feschotte},

url = {https://doi.org/10.1186/s13059-018-1577-z},

doi = {10.1186/s13059-018-1577-z},

issn = {1474-760X},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Genome Biology},

volume = {19},

number = {1},

pages = {199},

abstract = {Transposable elements (TEs) are major components of eukaryotic genomes. However, the extent of their impact on genome evolution, function, and disease remain a matter of intense interrogation. The rise of genomics and large-scale functional assays has shed new light on the multi-faceted activities of TEs and implies that they should no longer be marginalized. Here, we introduce the fundamental properties of TEs and their complex interactions with their cellular environment, which are crucial to understanding their impact and manifold consequences for organismal biology. While we draw examples primarily from mammalian systems, the core concepts outlined here are relevant to a broad range of organisms.},

keywords = {Aicardi-Goutieres Syndrome, Endogenous Retroviruses (ERV), Human Endogenous Retroviruses (HERVs), Syncytin, transposable elements},

pubstate = {published},

tppubtype = {article}

}

@article{caron_very_2018,

title = {Very long intergenic non-coding RNA transcripts and expression profiles are associated to specific childhood acute lymphoblastic leukemia subtypes},

author = {Maxime Caron and Pascal St-Onge and Simon Drouin and Chantal Richer and Thomas Sontag and Stephan Busche and Guillaume Bourque and Tomi Pastinen and Daniel Sinnett},

url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207250},

doi = {10.1371/journal.pone.0207250},

issn = {1932-6203},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {PLOS ONE},

volume = {13},

number = {11},

pages = {e0207250},

abstract = {Very long intergenic non-coding RNAs (vlincRNAs) are a novel class of long transcripts (textasciitilde50 kb to 1 Mb) with cell type- or cancer-specific expression. We report the discovery and characterization of 256 vlincRNAs from a cohort of 64 primary childhood pre-B and pre-T acute lymphoblastic leukemia (cALL) samples, of which 61% are novel and specifically expressed in cALL. Validation was performed in 35 pre-B and pre-T cALL primary samples. We show that their expression is cALL immunophenotype and molecular subtype-specific and correlated with epigenetic modifications on their promoters, much like protein-coding genes. While the biological functions of these vlincRNAs are still unknown, our results suggest they could play a role in cALL etiology or progression.},

note = {Publisher: Public Library of Science},

keywords = {Blood, Cancers and neoplasms, Chromatin, DNA methylation, epigenetics, Histones, Human genomics, RNA sequencing},

pubstate = {published},

tppubtype = {article}

}

@article{goerner-potvin_computational_2018,

title = {Computational tools to unmask transposable elements},

author = {Patricia Goerner-Potvin and Guillaume Bourque},

url = {https://www.nature.com/articles/s41576-018-0050-x},

doi = {10.1038/s41576-018-0050-x},

issn = {1471-0064},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Nature Reviews Genetics},

volume = {19},

number = {11},

pages = {688--704},

abstract = {A substantial proportion of the genome of many species is derived from transposable elements (TEs). Moreover, through various self-copying mechanisms, TEs continue to proliferate in the genomes of most species. TEs have contributed numerous regulatory, transcript and protein innovations and have also been linked to disease. However, notwithstanding their demonstrated impact, many genomic studies still exclude them because their repetitive nature results in various analytical complexities. Fortunately, a growing array of methods and software tools are being developed to cater for them. This Review presents a summary of computational resources for TEs and highlights some of the challenges and remaining gaps to perform comprehensive genomic analyses that do not simply ‘mask’ repeats.},

note = {Number: 11 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{maani_tamoxifen_2018,

title = {Tamoxifen therapy in a murine model of myotubular myopathy},

author = {Nika Maani and Nesrin Sabha and Kamran Rezai and Arun Ramani and Linda Groom and Nadine Eltayeb and Faranak Mavandadnejad and Andrea Pang and Giulia Russo and Michael Brudno and Volker Haucke and Robert T Dirksen and James J Dowling},

url = {https://www.nature.com/articles/s41467-018-07057-5},

doi = {10.1038/s41467-018-07057-5},

issn = {2041-1723},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-19},

journal = {Nature Communications},

volume = {9},

number = {1},

pages = {4849},

abstract = {Myotubular myopathy (MTM) is a severe X-linked disease without existing therapies. Here, we show that tamoxifen ameliorates MTM-related histopathological and functional abnormalities in mice, and nearly doubles survival. The beneficial effects of tamoxifen are mediated primarily via estrogen receptor signaling, as demonstrated through in vitro studies and in vivo phenotypic rescue with estradiol. RNA sequencing and protein expression analyses revealed that rescue is mediated in part through post-transcriptional reduction of dynamin-2, a known MTM modifier. These findings demonstrate an unexpected ability of tamoxifen to improve the murine MTM phenotype, providing preclinical evidence to support clinical translation.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{zhao_peroxisome_2018,

title = {Peroxisome Proliferator-Activated Receptor–δ Supports the Metabolic Requirements of Cell Growth in TCRβ-Selected Thymocytes and Peripheral CD4+ Ŧ Cells},

author = {Fei Linda Zhao and Jeeyoon Jennifer Ahn and Edward L Y Chen and Tae Joon Yi and Natalie H Stickle and David Spaner and Juan Carlos Zúñiga-Pflücker and Shannon E Dunn},

url = {https://www.jimmunol.org/content/201/9/2664},

doi = {10.4049/jimmunol.1800374},

issn = {0022-1767, 1550-6606},

year  = {2018},

date = {2018-01-01},

urldate = {2021-05-26},

journal = {The Journal of Immunology},

volume = {201},

number = {9},

pages = {2664--2682},

abstract = {During T cell development, progenitor thymocytes undergo a large proliferative burst immediately following successful TCRβ rearrangement, and defects in genes that regulate this proliferation have a profound effect on thymus cellularity and output. Although the signaling pathways that initiate cell cycling and nutrient uptake after TCRβ selection are understood, less is known about the transcriptional programs that regulate the metabolic machinery to promote biomass accumulation during this process. In this article, we report that mice with whole body deficiency in the nuclear receptor peroxisome proliferator-activated receptor–δ (PPARδmut) exhibit a reduction in spleen and thymus cellularity, with a decrease in thymocyte cell number starting at the double-negative 4 stage of thymocyte development. Although in vivo DNA synthesis was normal in PPARδmut thymocytes, studies in the OP9–delta-like 4 in vitro system of differentiation revealed that PPARδmut double-negative 3 cells underwent fewer cell divisions. Naive CD4+ T cells from PPARδmut mice also exhibited reduced proliferation upon TCR and CD28 stimulation in vitro. Growth defects in PPAR-δ–deficient thymocytes and peripheral CD4+ T cells correlated with decreases in extracellular acidification rate, mitochondrial reserve, and expression of a host of genes involved in glycolysis, oxidative phosphorylation, and lipogenesis. By contrast, mice with T cell–restricted deficiency of Ppard starting at the double-positive stage of thymocyte development, although exhibiting defective CD4+ T cell growth, possessed a normal T cell compartment, pointing to developmental defects as a cause of peripheral T cell lymphopenia in PPARδmut mice. These findings implicate PPAR-δ as a regulator of the metabolic program during thymocyte and T cell growth.},

note = {Publisher: American Association of Immunologists 

Section: IMMUNE SYSTEM DEVELOPMENT},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29100083b,

title = {High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies},

author = {Fadi F Hamdan and Candace T Myers and Patrick Cossette and Philippe Lemay and Dan Spiegelman and Alexandre Dionne Laporte and Christina Nassif and Ousmane Diallo and Jean Monlong and Maxime Cadieux-Dion and Sylvia Dobrzeniecka and Caroline Meloche and Kyle Retterer and Megan T Cho and Jill A Rosenfeld and Weimin Bi and Christine Massicotte and Marguerite Miguet and Ledia Brunga and Brigid M Regan and Kelly Mo and Cory Tam and Amy Schneider and Georgie Hollingsworth and  and David R FitzPatrick and Alan Donaldson and Natalie Canham and Edward Blair and Bronwyn Kerr and Andrew E Fry and Rhys H Thomas and Joss Shelagh and Jane A Hurst and Helen Brittain and Moira Blyth and Robert Roger Lebel and Erica H Gerkes and Laura Davis-Keppen and Quinn Stein and Wendy K Chung and Sara J Dorison and Paul J Benke and Emily Fassi and Nicole Corsten-Janssen and Erik-Jan Kamsteeg and Frederic T Mau-Them and Ange-Line Bruel and Alain Verloes and Katrin Õunap and Monica H Wojcik and Dara V F Albert and Sunita Venkateswaran and Tyson Ware and Dean Jones and Yu-Chi Liu and Shekeeb S Mohammad and Peyman Bizargity and Carlos A Bacino and Vincenzo Leuzzi and Simone Martinelli and Bruno Dallapiccola and Marco Tartaglia and Lubov Blumkin and Klaas J Wierenga and Gabriela Purcarin and James J O'Byrne and Sylvia Stockler and Anna Lehman and Boris Keren and Marie-Christine Nougues and Cyril Mignot and Stéphane Auvin and Caroline Nava and Susan M Hiatt and Martina Bebin and Yunru Shao and Fernando Scaglia and Seema R Lalani and Richard E Frye and Imad T Jarjour and Stéphanie Jacques and Renee-Myriam Boucher and Emilie Riou and Myriam Srour and Lionel Carmant and Anne Lortie and Philippe Major and Paola Diadori and François Dubeau and Guy D'Anjou and Guillaume Bourque and Samuel F Berkovic and Lynette G Sadleir and Philippe M Campeau and Zoha Kibar and Ronald G Lafrenière and Simon L Girard and Saadet Mercimek-Mahmutoglu and Cyrus Boelman and Guy A Rouleau and Ingrid E Scheffer and Heather C Mefford and Danielle M Andrade and Elsa Rossignol and Berge A Minassian and Jacques L Michaud},

doi = {10.1016/j.ajhg.2017.09.008},

issn = {1537-6605},

year  = {2017},

date = {2017-11-01},

journal = {Am J Hum Genet},

volume = {101},

number = {5},

pages = {664--685},

abstract = {Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the majority of cases. We performed whole-genome sequencing (WGS) in 197 individuals with unexplained DEE and pharmaco-resistant seizures and in their unaffected parents. We focused our attention on de novo mutations (DNMs) and identified candidate genes containing such variants. We sought to identify additional subjects with DNMs in these genes by performing targeted sequencing in another series of individuals with DEE and by mining various sequencing datasets. We also performed meta-analyses to document enrichment of DNMs in candidate genes by leveraging our WGS dataset with those of several DEE and ID series. By combining these strategies, we were able to provide a causal link between DEE and the following genes: NTRK2, GABRB2, CLTC, DHDDS, NUS1, RAB11A, GABBR2, and SNAP25. Overall, we established a molecular diagnosis in 63/197 (32%) individuals in our WGS series. The main cause of DEE in these individuals was de novo point mutations (53/63 solved cases), followed by inherited mutations (6/63 solved cases) and de novo CNVs (4/63 solved cases). De novo missense variants explained a larger proportion of individuals in our series than in other series that were primarily ascertained because of ID. Moreover, these DNMs were more frequently recurrent than those identified in ID series. These observations indicate that the genetic landscape of DEE might be different from that of ID without epilepsy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28789839b,

title = {Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls},

author = {Céline Bellenguez and Camille Charbonnier and Benjamin Grenier-Boley and Olivier Quenez and Kilan Le Guennec and Gaël Nicolas and Ganesh Chauhan and David Wallon and Stéphane Rousseau and Anne Claire Richard and Anne Boland and Guillaume Bourque and Hans Markus Munter and Robert Olaso and Vincent Meyer and Adeline Rollin-Sillaire and Florence Pasquier and Luc Letenneur and Richard Redon and Jean-François Dartigues and Christophe Tzourio and Thierry Frebourg and Mark Lathrop and Jean-François Deleuze and Didier Hannequin and Emmanuelle Genin and Philippe Amouyel and Stéphanie Debette and Jean-Charles Lambert and Dominique Campion and },

doi = {10.1016/j.neurobiolaging.2017.07.001},

issn = {1558-1497},

year  = {2017},

date = {2017-11-01},

journal = {Neurobiol Aging},

volume = {59},

pages = {220.e1--220.e9},

abstract = {We performed whole-exome and whole-genome sequencing in 927 late-onset Alzheimer disease (LOAD) cases, 852 early-onset AD (EOAD) cases, and 1273 controls from France. We assessed the evidence for gene-based association of rare variants with AD in 6 genes for which an association with such variants was previously claimed. When aggregating protein-truncating and missense-predicted damaging variants, we found exome-wide significant association between EOAD risk and rare variants in SORL1, TREM2, and ABCA7. No exome-wide significant signal was obtained in the LOAD sample, and significance of the order of 10 was observed in the whole AD group for TREM2. Our study confirms previous gene-level results for TREM2, SORL1, and ABCA7 and provides a clearer insight into the classes of rare variants involved. Despite different effect sizes and varying cumulative minor allele frequencies, the rare protein-truncating and missense-predicted damaging variants in TREM2, SORL1, and ABCA7 contribute similarly to the heritability of EOAD and explain between 1.1% and 1.5% of EOAD heritability each, compared with 9.12% for APOE ε4.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28724614b,

title = {Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer},

author = {Étienne Audet-Walsh and Catherine R Dufour and Tracey Yee and Fatima Z Zouanat and Ming Yan and Georges Kalloghlian and Mathieu Vernier and Maxime Caron and Guillaume Bourque and Eleonora Scarlata and Lucie Hamel and Fadi Brimo and Armen G Aprikian and Jacques Lapointe and Simone Chevalier and Vincent Giguère},

doi = {10.1101/gad.299958.117},

issn = {1549-5477},

year  = {2017},

date = {2017-06-01},

journal = {Genes Dev},

volume = {31},

number = {12},

pages = {1228--1242},

abstract = {Androgen receptor (AR) signaling reprograms cellular metabolism to support prostate cancer (PCa) growth and survival. Another key regulator of cellular metabolism is mTOR, a kinase found in diverse protein complexes and cellular localizations, including the nucleus. However, whether nuclear mTOR plays a role in PCa progression and participates in direct transcriptional cross-talk with the AR is unknown. Here, via the intersection of gene expression, genomic, and metabolic studies, we reveal the existence of a nuclear mTOR-AR transcriptional axis integral to the metabolic rewiring of PCa cells. Androgens reprogram mTOR-chromatin associations in an AR-dependent manner in which activation of mTOR-dependent metabolic gene networks is essential for androgen-induced aerobic glycolysis and mitochondrial respiration. In models of castration-resistant PCa cells, mTOR was capable of transcriptionally regulating metabolic gene programs in the absence of androgens, highlighting a potential novel castration resistance mechanism to sustain cell metabolism even without a functional AR. Remarkably, we demonstrate that increased mTOR nuclear localization is indicative of poor prognosis in patients, with the highest levels detected in castration-resistant PCa tumors and metastases. Identification of a functional mTOR targeted multigene signature robustly discriminates between normal prostate tissues, primary tumors, and hormone refractory metastatic samples but is also predictive of cancer recurrence. This study thus underscores a paradigm shift from AR to nuclear mTOR as being the master transcriptional regulator of metabolism in PCa.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{M2017b,

title = {Noninvasive Prenatal Detection of Trisomy 21 by Targeted Semiconductor Sequencing: A Technical Feasibility Study},

author = {Brudno M},

url = {https://www.karger.com/Article/Abstract/460248#},

doi = {https://doi.org/10.1159/000460248},

year  = {2017},

date = {2017-05-17},

abstract = {To develop an alternate noninvasive prenatal testing method for the assessment of trisomy 21 (T21) using a targeted semiconductor sequencing approach. Methods: A customized AmpliSeq panel was designed with 1,067 primer pairs targeting specific regions on chromosomes 21, 18, 13, and others. A total of 235 samples, including 30 affected with T21, were sequenced with an Ion Torrent Proton sequencer, and a method was developed for assessing the probability of fetal aneuploidy via derivation of a risk score. Results: Application of the derived risk score yields a bimodal distribution, with the affected samples clustering near 1.0 and the unaffected near 0. For a risk score cutoff of 0.345, above which all would be considered at “high risk,” all 30 T21-positive pregnancies were correctly predicted to be affected, and 199 of the 205 non-T21 samples were correctly predicted. The average hands-on time spent on library preparation and sequencing was 19 h in total, and the average number of reads of sequence obtained was 3.75 million per sample. Conclusion: With the described targeted sequencing approach on the semiconductor platform using a custom-designed library and a probabilistic statistical approach, we have demonstrated the feasibility of an alternate method of assessment for fetal T21.},

keywords = {Cell-free fetal DNA, Noninvasive prenatal testing, Semiconductor sequencing, Trisomy 21},

pubstate = {published},

tppubtype = {article}

}

@article{KM2017,

title = {International Cooperation to Enable the Diagnosis of All Rare Genetic Diseases},

author = {Brudno M,},

url = {https://www.cell.com/ajhg/fulltext/S0002-9297(17)30147-7},

doi = {https://doi.org/10.1016/j.ajhg.2017.04.003},

year  = {2017},

date = {2017-05-06},

abstract = {Provision of a molecularly confirmed diagnosis in a timely manner for children and adults with rare genetic diseases shortens their “diagnostic odyssey,” improves disease management, and fosters genetic counseling with respect to recurrence risks while assuring reproductive choices. In a general clinical genetics setting, the current diagnostic rate is approximately 50%, but for those who do not receive a molecular diagnosis after the initial genetics evaluation, that rate is much lower. Diagnostic success for these more challenging affected individuals depends to a large extent on progress in the discovery of genes associated with, and mechanisms underlying, rare diseases. Thus, continued research is required for moving toward a more complete catalog of disease-related genes and variants. The International Rare Diseases Research Consortium (IRDiRC) was established in 2011 to bring together researchers and organizations invested in rare disease research to develop a means of achieving molecular diagnosis for all rare diseases. Here, we review the current and future bottlenecks to gene discovery and suggest strategies for enabling progress in this regard. Each successful discovery will define potential diagnostic, preventive, and therapeutic opportunities for the corresponding rare disease, enabling precision medicine for this patient population.},

keywords = {DNA, Rare},

pubstate = {published},

tppubtype = {article}

}

@article{Brudno2017,

title = {CHARGE and Kabuki Syndromes: Gene-Specific DNA Methylation Signatures Identify Epigenetic Mechanisms Linking These Clinically Overlapping Conditions},

author = {Michael Brudno},

url = {https://www.cell.com/ajhg/fulltext/S0002-9297(17)30148-9},

doi = {DOI:https://doi.org/10.1016/j.ajhg.2017.04.004},

year  = {2017},

date = {2017-05-04},

abstract = {Epigenetic dysregulation has emerged as a recurring mechanism in the etiology of neurodevelopmental disorders. Two such disorders, CHARGE and Kabuki syndromes, result from loss of function mutations in chromodomain helicase DNA-binding protein 7 (CHD7LOF) and lysine (K) methyltransferase 2D (KMT2DLOF), respectively. Although these two syndromes are clinically distinct, there is significant phenotypic overlap. We therefore expected that epigenetically driven developmental pathways regulated by CHD7 and KMT2D would overlap and that DNA methylation (DNAm) alterations downstream of the mutations in these genes would identify common target genes, elucidating a mechanistic link between these two conditions, as well as specific target genes for each disorder. Genome-wide DNAm profiles in individuals with CHARGE and Kabuki syndromes with CHD7LOF or KMT2DLOF identified distinct sets of DNAm differences in each of the disorders, which were used to generate two unique, highly specific and sensitive DNAm signatures. These DNAm signatures were able to differentiate pathogenic mutations in these two genes from controls and from each other. Analysis of the DNAm targets in each gene-specific signature identified both common gene targets, including homeobox A5 (HOXA5), which could account for some of the clinical overlap in CHARGE and Kabuki syndromes, as well as distinct gene targets. Our findings demonstrate how characterization of the epigenome can contribute to our understanding of disease pathophysiology for epigenetic disorders, paving the way for explorations of novel therapeutics.},

keywords = {DNA, Methylation},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28332632b,

title = {Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma},

author = {Madeleine Arseneault and Jean Monlong and Naveen S Vasudev and Ruhina S Laskar and Maryam Safisamghabadi and Patricia Harnden and Lars Egevad and Nazanin Nourbehesht and Pudchalaluck Panichnantakul and Ivana Holcatova and Antonin Brisuda and Vladimir Janout and Helena Kollarova and Lenka Foretova and Marie Navratilova and Dana Mates and Viorel Jinga and David Zaridze and Anush Mukeria and Pouria Jandaghi and Paul Brennan and Alvis Brazma and Jorg Tost and Ghislaine Scelo and Rosamonde E Banks and Mark Lathrop and Guillaume Bourque and Yasser Riazalhosseini},

doi = {10.1038/srep44876},

issn = {2045-2322},

year  = {2017},

date = {2017-03-01},

journal = {Sci Rep},

volume = {7},

pages = {44876},

abstract = {Recent genomic studies of sporadic clear cell renal cell carcinoma (ccRCC) have uncovered novel driver genes and pathways. Given the unequal incidence rates among men and women (male:female incidence ratio approaches 2:1), we compared the genome-wide distribution of the chromosomal abnormalities in both sexes. We observed a higher frequency for the somatic recurrent chromosomal copy number variations (CNVs) of autosomes in male subjects, whereas somatic loss of chromosome X was detected exclusively in female patients (17.1%). Furthermore, somatic loss of chromosome Y (LOY) was detected in about 40% of male subjects, while mosaic LOY was detected in DNA isolated from peripheral blood in 9.6% of them, and was the only recurrent CNV in constitutional DNA samples. LOY in constitutional DNA, but not in tumor DNA was associated with older age. Amongst Y-linked genes that were downregulated due to LOY, KDM5D and KDM6C epigenetic modifiers have functionally-similar X-linked homologs whose deficiency is involved in ccRCC progression. Our findings establish somatic LOY as a highly recurrent genetic defect in ccRCC that leads to downregulation of hitherto unsuspected epigenetic factors, and suggest that different mechanisms may underlie the somatic and mosaic LOY observed in tumors and peripheral blood, respectively.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28290481b,

title = {Identification of Elongated Primary Cilia with Impaired Mechanotransduction in Idiopathic Scoliosis Patients},

author = {Niaz Oliazadeh and Kristen F Gorman and Robert Eveleigh and Guillaume Bourque and Alain Moreau},

doi = {10.1038/srep44260},

issn = {2045-2322},

year  = {2017},

date = {2017-03-01},

journal = {Sci Rep},

volume = {7},

pages = {44260},

abstract = {The primary cilium is an outward projecting antenna-like organelle with an important role in bone mechanotransduction. The capacity to sense mechanical stimuli can affect important cellular and molecular aspects of bone tissue. Idiopathic scoliosis (IS) is a complex pediatric disease of unknown cause, defined by abnormal spinal curvatures. We demonstrate significant elongation of primary cilia in IS patient bone cells. In response to mechanical stimulation, these IS cells differentially express osteogenic factors, mechanosensitive genes, and signaling genes. Considering that numerous ciliary genes are associated with a scoliosis phenotype, among ciliopathies and knockout animal models, we expected IS patients to have an accumulation of rare variants in ciliary genes. Instead, our SKAT-O analysis of whole exomes showed an enrichment among IS patients for rare variants in genes with a role in cellular mechanotransduction. Our data indicates defective cilia in IS bone cells, which may be linked to heterogeneous gene variants pertaining to cellular mechanotransduction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28283040b,

title = {Functional variation in allelic methylomes underscores a strong genetic contribution and reveals novel epigenetic alterations in the human epigenome},

author = {Warren A Cheung and Xiaojian Shao and Andréanne Morin and Valérie Siroux and Tony Kwan and Bing Ge and Dylan Aïssi and Lu Chen and Louella Vasquez and Fiona Allum and Frédéric Guénard and Emmanuelle Bouzigon and Marie-Michelle Simon and Elodie Boulier and Adriana Redensek and Stephen Watt and Avik Datta and Laura Clarke and Paul Flicek and Daniel Mead and Dirk S Paul and Stephan Beck and Guillaume Bourque and Mark Lathrop and André Tchernof and Marie-Claude Vohl and Florence Demenais and Isabelle Pin and Kate Downes and Hendrick G Stunnenberg and Nicole Soranzo and Tomi Pastinen and Elin Grundberg},

doi = {10.1186/s13059-017-1173-7},

issn = {1474-760X},

year  = {2017},

date = {2017-03-01},

journal = {Genome Biol},

volume = {18},

number = {1},

pages = {50},

abstract = {BACKGROUND: The functional impact of genetic variation has been extensively surveyed, revealing that genetic changes correlated to phenotypes lie mostly in non-coding genomic regions. Studies have linked allele-specific genetic changes to gene expression, DNA methylation, and histone marks but these investigations have only been carried out in a limited set of samples.



RESULTS: We describe a large-scale coordinated study of allelic and non-allelic effects on DNA methylation, histone mark deposition, and gene expression, detecting the interrelations between epigenetic and functional features at unprecedented resolution. We use information from whole genome and targeted bisulfite sequencing from 910 samples to perform genotype-dependent analyses of allele-specific methylation (ASM) and non-allelic methylation (mQTL). In addition, we introduce a novel genotype-independent test to detect methylation imbalance between chromosomes. Of the ~2.2 million CpGs tested for ASM, mQTL, and genotype-independent effects, we identify ~32% as being genetically regulated (ASM or mQTL) and ~14% as being putatively epigenetically regulated. We also show that epigenetically driven effects are strongly enriched in repressed regions and near transcription start sites, whereas the genetically regulated CpGs are enriched in enhancers. Known imprinted regions are enriched among epigenetically regulated loci, but we also observe several novel genomic regions (e.g., HOX genes) as being epigenetically regulated. Finally, we use our ASM datasets for functional interpretation of disease-associated loci and show the advantage of utilizing naïve T cells for understanding autoimmune diseases.



CONCLUSIONS: Our rich catalogue of haploid methylomes across multiple tissues will allow validation of epigenome association studies and exploration of new biological models for allelic exclusion in the human genome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27797775,

title = {Optimizing ChIP-seq peak detectors using visual labels and supervised machine learning},

author = {Toby Dylan Hocking and Patricia Goerner-Potvin and Andreanne Morin and Xiaojian Shao and Tomi Pastinen and Guillaume Bourque},

doi = {10.1093/bioinformatics/btw672},

issn = {1367-4811},

year  = {2017},

date = {2017-02-01},

journal = {Bioinformatics},

volume = {33},

number = {4},

pages = {491--499},

abstract = {MOTIVATION: Many peak detection algorithms have been proposed for ChIP-seq data analysis, but it is not obvious which algorithm and what parameters are optimal for any given dataset. In contrast, regions with and without obvious peaks can be easily labeled by visual inspection of aligned read counts in a genome browser. We propose a supervised machine learning approach for ChIP-seq data analysis, using labels that encode qualitative judgments about which genomic regions contain or do not contain peaks. The main idea is to manually label a small subset of the genome, and then learn a model that makes consistent peak predictions on the rest of the genome.



RESULTS: We created 7 new histone mark datasets with 12 826 visually determined labels, and analyzed 3 existing transcription factor datasets. We observed that default peak detection parameters yield high false positive rates, which can be reduced by learning parameters using a relatively small training set of labeled data from the same experiment type. We also observed that labels from different people are highly consistent. Overall, these data indicate that our supervised labeling method is useful for quantitatively training and testing peak detection algorithms.



AVAILABILITY AND IMPLEMENTATION: Labeled histone mark data http://cbio.ensmp.fr/~thocking/chip-seq-chunk-db/ , R package to compute the label error of predicted peaks https://github.com/tdhock/PeakError.



CONTACTS: toby.hocking@mail.mcgill.ca or guil.bourque@mcgill.ca.



SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28245871b,

title = {Conserved expression of transposon-derived non-coding transcripts in primate stem cells},

author = {LeeAnn Ramsay and Maria C Marchetto and Maxime Caron and Shu-Huang Chen and Stephan Busche and Tony Kwan and Tomi Pastinen and Fred H Gage and Guillaume Bourque},

doi = {10.1186/s12864-017-3568-y},

issn = {1471-2164},

year  = {2017},

date = {2017-02-01},

journal = {BMC Genomics},

volume = {18},

number = {1},

pages = {214},

abstract = {BACKGROUND: A significant portion of expressed non-coding RNAs in human cells is derived from transposable elements (TEs). Moreover, it has been shown that various long non-coding RNAs (lncRNAs), which come from the human endogenous retrovirus subfamily H (HERVH), are not only expressed but required for pluripotency in human embryonic stem cells (hESCs).



RESULTS: To identify additional TE-derived functional non-coding transcripts, we generated RNA-seq data from induced pluripotent stem cells (iPSCs) of four primate species (human, chimpanzee, gorilla, and rhesus) and searched for transcripts whose expression was conserved. We observed that about 30% of TE instances expressed in human iPSCs had orthologous TE instances that were also expressed in chimpanzee and gorilla. Notably, our analysis revealed a number of repeat families with highly conserved expression profiles including HERVH but also MER53, which is known to be the source of a placental-specific family of microRNAs (miRNAs). We also identified a number of repeat families from all classes of TEs, including MLT1-type and Tigger families, that contributed a significant amount of sequence to primate lncRNAs whose expression was conserved.



CONCLUSIONS: Together, these results describe TE families and TE-derived lncRNAs whose conserved expression patterns can be used to identify what are likely functional TE-derived non-coding transcripts in primate iPSCs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Su2017,

title = {Retrotransposon-Derived Regulatory Regions and Transcripts in Stemness},

author = {Zhaohui Su, Guillaume Bourque},

url = {https://link.springer.com/chapter/10.1007/978-3-319-48344-3_8#citeas},

doi = {DOI https://doi.org/10.1007/978-3-319-48344-3_8},

year  = {2017},

date = {2017-01-04},

abstract = {Transposable elements (TEs) have contributed greatly to the regulatory landscape of many cell types, including to human embryonic stem cells. In this chapter we summarize recent studies that have shown that TE insertions have silenced nearby genes, introduced transcription factor-binding sites, as well as produced novel transcripts including those that are translated into viral particles and those that are functional as noncoding RNA. We focus on presenting results on human and other mammalian pluripotent stem cells because of their importance in studying human health and evolution. Finally we also discuss the applications, implications, and questions that are raised from this newfound knowledge.},

keywords = {Embryonic stem cells, ion, Long noncoding RNAs, transposable elements},

pubstate = {published},

tppubtype = {article}

}

@article{yanitch_transcriptomic_2017,

title = {Transcriptomic Response of Purple Willow (Salix purpurea) to Arsenic Stress},

author = {Aymeric Yanitch and Nicholas J B Brereton and Emmanuel Gonzalez and Michel Labrecque and Simon Joly and Frederic E Pitre},

url = {https://www.frontiersin.org/articles/10.3389/fpls.2017.01115/full},

doi = {10.3389/fpls.2017.01115},

issn = {1664-462X},

year  = {2017},

date = {2017-01-01},

urldate = {2021-05-18},

journal = {Frontiers in Plant Science},

volume = {8},

abstract = {Arsenic (As) is a toxic element for plants and one of the most common anthropogenic pollutants found at contaminated sites. Despite its severe effects on plant metabolism, several species can accumulate substantial amounts of arsenic and endure the associated stress. However, the genetic mechanisms involved in arsenic tolerance remains obscure in many model plant species used for land decontamination (phytoremediation), including willows. The present study assesses the potential of Salix purpurea cv. ‘Fish Creek’ for arsenic phytoextraction and reveals the genetic responses behind arsenic tolerance, phytoextraction and metabolism. Four weeks of hydroponic exposure to 0, 5, 30 and 100 mg/L revealed that plants were able to tolerate up to 5 mg/L arsenic. Concentrations of 0 and 5 mg/L of arsenic treatment were then used to compare alterations in gene expression of roots, stems and leaves using RNA sequencing. Differential gene expression revealed transcripts encoding proteins putatively involved in entry of arsenic into the roots, storage in vacuoles and potential transport through the plant as well as primary and secondary (indirect) toxicity tolerance mechanisms. A major role for tannin as a compound used to relieve cellular toxicity is implicated as well as unexpected expression of the cadmium transporter CAX2, providing a potential means for internal arsenic mobility. These insights into the underpinning genetics of a successful phytoremediating species present novel opportunities for selection of dedicated arsenic tolerant crops as well as the potential to integrate such tolerances into a wider Salix ideotype alongside traits including biomass yield, biomass quality, low agricultural inputs and phytochemical production.},

note = {Publisher: Frontiers},

keywords = {Abiotic stress tolerance, Arsenic, Phytoremediation, RNA-seq, Salix, Trace Elements, Transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{dyke_matching_2017,

title = {“Matching” consent to purpose: The example of the Matchmaker Exchange},

author = {Stephanie O M Dyke and Bartha M Knoppers and Ada Hamosh and Helen V Firth and Matthew Hurles and Michael Brudno and Kym M Boycott and Anthony A Philippakis and Heidi L Rehm},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.23278},

doi = {https://doi.org/10.1002/humu.23278},

issn = {1098-1004},

year  = {2017},

date = {2017-01-01},

urldate = {2021-05-18},

journal = {Human Mutation},

volume = {38},

number = {10},

pages = {1281--1285},

abstract = {The Matchmaker Exchange (MME) connects rare disease clinicians and researchers to facilitate the sharing of data from undiagnosed patients for the purpose of novel gene discovery. Such sharing raises the odds that two or more similar patients with candidate genes in common may be found, thereby allowing their condition to be more readily studied and understood. Consent considerations for data sharing in MME included both the ethical and legal differences between clinical and research settings and the level of privacy risk involved in sharing varying amounts of rare disease patient data to enable patient matches. In this commentary, we discuss these consent considerations and the resulting MME Consent Policy as they may be relevant to other international data sharing initiatives.},

note = {_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/humu.23278},

keywords = {consent, data access, data sharing, personalized medicine, precision medicine, privacy},

pubstate = {published},

tppubtype = {article}

}

@article{audet-walsh_nuclear_2017,

title = {Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer},

author = {Étienne Audet-Walsh and Catherine R Dufour and Tracey Yee and Fatima Z Zouanat and Ming Yan and Georges Kalloghlian and Mathieu Vernier and Maxime Caron and Guillaume Bourque and Eleonora Scarlata and Lucie Hamel and Fadi Brimo and Armen G Aprikian and Jacques Lapointe and Simone Chevalier and Vincent Giguère},

url = {http://genesdev.cshlp.org/content/31/12/1228},

doi = {10.1101/gad.299958.117},

issn = {0890-9369, 1549-5477},

year  = {2017},

date = {2017-01-01},

urldate = {2021-05-18},

journal = {Genes & Development},

volume = {31},

number = {12},

pages = {1228--1242},

abstract = {Androgen receptor (AR) signaling reprograms cellular metabolism to support prostate cancer (PCa) growth and survival. Another key regulator of cellular metabolism is mTOR, a kinase found in diverse protein complexes and cellular localizations, including the nucleus. However, whether nuclear mTOR plays a role in PCa progression and participates in direct transcriptional cross-talk with the AR is unknown. Here, via the intersection of gene expression, genomic, and metabolic studies, we reveal the existence of a nuclear mTOR–AR transcriptional axis integral to the metabolic rewiring of PCa cells. Androgens reprogram mTOR–chromatin associations in an AR-dependent manner in which activation of mTOR-dependent metabolic gene networks is essential for androgen-induced aerobic glycolysis and mitochondrial respiration. In models of castration-resistant PCa cells, mTOR was capable of transcriptionally regulating metabolic gene programs in the absence of androgens, highlighting a potential novel castration resistance mechanism to sustain cell metabolism even without a functional AR. Remarkably, we demonstrate that increased mTOR nuclear localization is indicative of poor prognosis in patients, with the highest levels detected in castration-resistant PCa tumors and metastases. Identification of a functional mTOR targeted multigene signature robustly discriminates between normal prostate tissues, primary tumors, and hormone refractory metastatic samples but is also predictive of cancer recurrence. This study thus underscores a paradigm shift from AR to nuclear mTOR as being the master transcriptional regulator of metabolism in PCa.},

note = {Company: Cold Spring Harbor Laboratory Press 

Distributor: Cold Spring Harbor Laboratory Press 

Institution: Cold Spring Harbor Laboratory Press 

Label: Cold Spring Harbor Laboratory Press 

Publisher: Cold Spring Harbor Lab},

keywords = {androgen receptor, ChIP-seq, CRPC, energy metabolism, nuclear receptor, steroid},

pubstate = {published},

tppubtype = {article}

}

@article{bellenguez_contribution_2017,

title = {Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls},

author = {Céline Bellenguez and Camille Charbonnier and Benjamin Grenier-Boley and Olivier Quenez and Kilan Le Guennec and Gaël Nicolas and Ganesh Chauhan and David Wallon and Stéphane Rousseau and Anne Claire Richard and Anne Boland and Guillaume Bourque and Hans Markus Munter and Robert Olaso and Vincent Meyer and Adeline Rollin-Sillaire and Florence Pasquier and Luc Letenneur and Richard Redon and Jean-François Dartigues and Christophe Tzourio and Thierry Frebourg and Mark Lathrop and Jean-François Deleuze and Didier Hannequin and Emmanuelle Genin and Philippe Amouyel and Stéphanie Debette and Jean-Charles Lambert and Dominique Campion and Didier Hannequin and Dominique Campion and David Wallon and Olivier Martinaud and Aline Zarea and Gaël Nicolas and Adeline Rollin-Sillaire and Stéphanie Bombois and Marie-Anne Mackowiak and Vincent Deramecourt and Florence Pasquier and Agnès Michon and Isabelle Le Ber and Bruno Dubois and Olivier Godefroy and Frédérique Etcharry-Bouyx and Valérie Chauviré and Ludivine Chamard and Eric Berger and Eloi Magnin and Jean-Francois Dartigues and Sophie Auriacombe and François Tison and Vincent de la Sayette and Dominique Castan and Elsa Dionet and Francois Sellal and Olivier Rouaud and Christel Thauvin and Olivier Moreaud and Mathilde Sauvée and Maïté Formaglio and Hélène Mollion and Isabelle Roullet-Solignac and Alain Vighetto and Bernard Croisile and Mira Didic and Olivier Félician and Lejla Koric and Mathieu Ceccaldi and Audrey Gabelle and Cecilia Marelli and Pierre Labauge and Thérèse Jonveaux and Martine Vercelletto and Claire Boutoleau-Bretonnière and Giovanni Castelnovo and Claire Paquet and Julien Dumurgier and Jacques Hugon and Foucauld De Boisgueheneuc and Serge Belliard and Serge Bakchine and Marie Sarazin and Marie-Odile Barrellon and Bernard Laurent and Frédéric Blanc and Jérémie Pariente and Snejana Jurici},

url = {https://www.sciencedirect.com/science/article/pii/S0197458017302324},

doi = {10.1016/j.neurobiolaging.2017.07.001},

issn = {0197-4580},

year  = {2017},

date = {2017-01-01},

urldate = {2021-05-18},

journal = {Neurobiology of Aging},

volume = {59},

pages = {220.e1--220.e9},

abstract = {We performed whole-exome and whole-genome sequencing in 927 late-onset Alzheimer disease (LOAD) cases, 852 early-onset AD (EOAD) cases, and 1273 controls from France. We assessed the evidence for gene-based association of rare variants with AD in 6 genes for which an association with such variants was previously claimed. When aggregating protein-truncating and missense-predicted damaging variants, we found exome-wide significant association between EOAD risk and rare variants in SORL1, TREM2, and ABCA7. No exome-wide significant signal was obtained in the LOAD sample, and significance of the order of 10−6 was observed in the whole AD group for TREM2. Our study confirms previous gene-level results for TREM2, SORL1, and ABCA7 and provides a clearer insight into the classes of rare variants involved. Despite different effect sizes and varying cumulative minor allele frequencies, the rare protein-truncating and missense-predicted damaging variants in TREM2, SORL1, and ABCA7 contribute similarly to the heritability of EOAD and explain between 1.1% and 1.5% of EOAD heritability each, compared with 9.12% for APOE ε4.},

keywords = {Alzheimer's disease},

pubstate = {published},

tppubtype = {article}

}

@article{wang_vicus_2017,

title = {Vicus: Exploiting local structures to improve network-based analysis of biological data},

author = {Bo Wang and Lin Huang and Yuke Zhu and Anshul Kundaje and Serafim Batzoglou and Anna Goldenberg},

url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005621},

doi = {10.1371/journal.pcbi.1005621},

issn = {1553-7358},

year  = {2017},

date = {2017-01-01},

urldate = {2021-05-19},

journal = {PLOS Computational Biology},

volume = {13},

number = {10},

pages = {e1005621},

abstract = {Biological networks entail important topological features and patterns critical to understanding interactions within complicated biological systems. Despite a great progress in understanding their structure, much more can be done to improve our inference and network analysis. Spectral methods play a key role in many network-based applications. Fundamental to spectral methods is the Laplacian, a matrix that captures the global structure of the network. Unfortunately, the Laplacian does not take into account intricacies of the network’s local structure and is sensitive to noise in the network. These two properties are fundamental to biological networks and cannot be ignored. We propose an alternative matrix Vicus. The Vicus matrix captures the local neighborhood structure of the network and thus is more effective at modeling biological interactions. We demonstrate the advantages of Vicus in the context of spectral methods by extensive empirical benchmarking on tasks such as single cell dimensionality reduction, protein module discovery and ranking genes for cancer subtyping. Our experiments show that using Vicus, spectral methods result in more accurate and robust performance in all of these tasks.},

note = {Publisher: Public Library of Science},

keywords = {Algebraic structures, Eigenvalues, Eigenvectors, Network analysis, Protein interaction networks, Protein structure comparison, Protein structure networks, Spectral clustering},

pubstate = {published},

tppubtype = {article}

}

@article{mezlini_incorporating_2017,

title = {Incorporating networks in a probabilistic graphical model to find drivers for complex human diseases},

author = {Aziz M Mezlini and Anna Goldenberg},

url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005580},

doi = {10.1371/journal.pcbi.1005580},

issn = {1553-7358},

year  = {2017},

date = {2017-01-01},

urldate = {2021-05-19},

journal = {PLOS Computational Biology},

volume = {13},

number = {10},

pages = {e1005580},

abstract = {Discovering genetic mechanisms driving complex diseases is a hard problem. Existing methods often lack power to identify the set of responsible genes. Protein-protein interaction networks have been shown to boost power when detecting gene-disease associations. We introduce a Bayesian framework, Conflux, to find disease associated genes from exome sequencing data using networks as a prior. There are two main advantages to using networks within a probabilistic graphical model. First, networks are noisy and incomplete, a substantial impediment to gene discovery. Incorporating networks into the structure of a probabilistic models for gene inference has less impact on the solution than relying on the noisy network structure directly. Second, using a Bayesian framework we can keep track of the uncertainty of each gene being associated with the phenotype rather than returning a fixed list of genes. We first show that using networks clearly improves gene detection compared to individual gene testing. We then show consistently improved performance of Conflux compared to the state-of-the-art diffusion network-based method Hotnet2 and a variety of other network and variant aggregation methods, using randomly generated and literature-reported gene sets. We test Hotnet2 and Conflux on several network configurations to reveal biases and patterns of false positives and false negatives in each case. Our experiments show that our novel Bayesian framework Conflux incorporates many of the advantages of the current state-of-the-art methods, while offering more flexibility and improved power in many gene-disease association scenarios.},

note = {Publisher: Public Library of Science},

keywords = {Cancers and neoplasms, Gene prediction, Genetic networks, Mutation, Ovarian cancer, Protein interaction networks, Protein-protein interactions, Schizophrenia},

pubstate = {published},

tppubtype = {article}

}

@article{hamdan_high_2017,

title = {High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies},

author = {Fadi F Hamdan and Candace T Myers and Patrick Cossette and Philippe Lemay and Dan Spiegelman and Alexandre Dionne Laporte and Christina Nassif and Ousmane Diallo and Jean Monlong and Maxime Cadieux-Dion and Sylvia Dobrzeniecka and Caroline Meloche and Kyle Retterer and Megan T Cho and Jill A Rosenfeld and Weimin Bi and Christine Massicotte and Marguerite Miguet and Ledia Brunga and Brigid M Regan and Kelly Mo and Cory Tam and Amy Schneider and Georgie Hollingsworth and David R FitzPatrick and Alan Donaldson and Natalie Canham and Edward Blair and Bronwyn Kerr and Andrew E Fry and Rhys H Thomas and Joss Shelagh and Jane A Hurst and Helen Brittain and Moira Blyth and Robert Roger Lebel and Erica H Gerkes and Laura Davis-Keppen and Quinn Stein and Wendy K Chung and Sara J Dorison and Paul J Benke and Emily Fassi and Nicole Corsten-Janssen and Erik-Jan Kamsteeg and Frederic T Mau-Them and Ange-Line Bruel and Alain Verloes and Katrin Õunap and Monica H Wojcik and Dara V F Albert and Sunita Venkateswaran and Tyson Ware and Dean Jones and Yu-Chi Liu and Shekeeb S Mohammad and Peyman Bizargity and Carlos A Bacino and Vincenzo Leuzzi and Simone Martinelli and Bruno Dallapiccola and Marco Tartaglia and Lubov Blumkin and Klaas J Wierenga and Gabriela Purcarin and James J O’Byrne and Sylvia Stockler and Anna Lehman and Boris Keren and Marie-Christine Nougues and Cyril Mignot and Stéphane Auvin and Caroline Nava and Susan M Hiatt and Martina Bebin and Yunru Shao and Fernando Scaglia and Seema R Lalani and Richard E Frye and Imad T Jarjour and Stéphanie Jacques and Renee-Myriam Boucher and Emilie Riou and Myriam Srour and Lionel Carmant and Anne Lortie and Philippe Major and Paola Diadori and François Dubeau and Guy D’Anjou and Guillaume Bourque and Samuel F Berkovic and Lynette G Sadleir and Philippe M Campeau and Zoha Kibar and Ronald G Lafrenière and Simon L Girard and Saadet Mercimek-Mahmutoglu and Cyrus Boelman and Guy A Rouleau and Ingrid E Scheffer and Heather C Mefford and Danielle M Andrade and Elsa Rossignol and Berge A Minassian and Jacques L Michaud},

url = {https://www.cell.com/ajhg/abstract/S0002-9297(17)30377-4},

doi = {10.1016/j.ajhg.2017.09.008},

issn = {0002-9297, 1537-6605},

year  = {2017},

date = {2017-01-01},

urldate = {2021-05-19},

journal = {The American Journal of Human Genetics},

volume = {101},

number = {5},

pages = {664--685},

note = {Publisher: Elsevier},

keywords = {CLTC, DHDDS, epileptic encephalopathy, GABBR2, GABRB2, NTRK2, NUS1, RAB11, SNAP25},

pubstate = {published},

tppubtype = {article}

}

@article{bourguinat_dirofilaria_2017,

title = {Dirofilaria immitis JYD-34 isolate: whole genome analysis},

author = {Catherine Bourguinat and Francois Lefebvre and Johanna Sandoval and Brenda Bondesen and Yovany Moreno and Roger K Prichard},

url = {https://doi.org/10.1186/s13071-017-2437-5},

doi = {10.1186/s13071-017-2437-5},

issn = {1756-3305},

year  = {2017},

date = {2017-01-01},

urldate = {2021-05-19},

journal = {Parasites & Vectors},

volume = {10},

number = {2},

pages = {494},

abstract = {Macrocyclic lactone (ML) anthelmintics are used for chemoprophylaxis for heartworm infection in dogs and cats. Cases of dogs becoming infected with heartworms, despite apparent compliance to recommended chemoprophylaxis with approved preventives, has led to such cases being considered as suspected lack of efficacy (LOE). Recently, microfilariae collected from a small number of LOE isolates were used as a source of infection of new host dogs and confirmed to have reduced susceptibility to ML in controlled efficacy studies using L3 challenge in dogs. A specific Dirofilaria immitis laboratory isolate named JYD-34 has also been confirmed to have less than 100% susceptibility to ML-based preventives. For preventive claims against heartworm disease, evidence of 100% efficacy is required by FDA-CVM. It was therefore of interest to determine whether JYD-34 has a genetic profile similar to other documented LOE and confirmed reduced susceptibility isolates or has a genetic profile similar to known ML-susceptible isolates.},

keywords = {Dirofilaria immitis, Heartworm preventives, JYD isolate, Macrocyclic lactone resistance, Whole genome analysis},

pubstate = {published},

tppubtype = {article}

}

@article{mamatjan_molecular_2017,

title = {Molecular Signatures for Tumor Classification: An Analysis of The Cancer Genome Atlas Data},

author = {Yasin Mamatjan and Sameer Agnihotri and Anna Goldenberg and Peter Tonge and Sheila Mansouri and Gelareh Zadeh and Kenneth Aldape},

url = {https://www.jmdjournal.org/article/S1525-1578(17)30202-7/abstract},

doi = {10.1016/j.jmoldx.2017.07.008},

issn = {1525-1578},

year  = {2017},

date = {2017-01-01},

urldate = {2021-05-19},

journal = {The Journal of Molecular Diagnostics},

volume = {19},

number = {6},

pages = {881--891},

abstract = {textlessptextgreaterCancer classification in the clinic is primarily based on histological analysis in the proper clinical context, often supplemented by immunohistochemical and molecular studies. Recent genomic studies have shown the potential of integrated multiomics platforms for molecular classification. We performed unsupervised analyses of molecular platforms in The Cancer Genome Atlas data (textitn = 6,216 samples) in comparison with tumor type. Our data showed that mRNA signatures and DNA methylation signatures mapped to histological diagnosis with high accuracy (95% and 88%, respectively) as individual platforms. The accuracy of mRNA signatures alone for classification and subtype identification was comparable to accuracies reported in the previously published Pan-Cancer 12 analysis. When combined, mRNA and methylation revealed a set of outliers for which the mRNA- and methylation-based molecular signatures concordantly differed from the original histological diagnosis. A subset remained consistent as outliers after using alternative classification and clustering algorithms and analysis of an independent molecular platform (miRNA). Overall, our results indicate that unsupervised approaches with individual genomic platforms, especially gene expression and DNA methylation, provide substantial classification information and identify occasional outlier cases in which the molecular signature is distinct from signatures expected for a given histological diagnosis. Identification of cases in which the molecular signature correlates with a specific histology that differs from initial impressions may prompt reconsideration of tumor classification in specific cases.textless/ptextgreater},

note = {Publisher: Elsevier},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{hayeems_care_2017,

title = {Care and cost consequences of pediatric whole genome sequencing compared to chromosome microarray},

author = {Robin Z Hayeems and Jasmin Bhawra and Kate Tsiplova and Stephen M Meyn and Nasim Monfared and Sarah Bowdin and James D Stavropoulos and Christian R Marshall and Raveen Basran and Cheryl Shuman and Shinya Ito and Iris Cohn and Courtney Hum and Marta Girdea and Michael Brudno and Ronald D Cohn and Stephen W Scherer and Wendy J Ungar},

url = {https://www.nature.com/articles/s41431-017-0020-3},

doi = {10.1038/s41431-017-0020-3},

issn = {1476-5438},

year  = {2017},

date = {2017-01-01},

urldate = {2021-05-19},

journal = {European Journal of Human Genetics},

volume = {25},

number = {12},

pages = {1303--1312},

abstract = {The clinical use of whole-genome sequencing (WGS) is expected to alter pediatric medical management. The study aimed to describe the type and cost of healthcare activities following pediatric WGS compared to chromosome microarray (CMA). Healthcare activities prompted by WGS and CMA were ascertained for 101 children with developmental delay over 1 year. Activities following receipt of non-diagnostic CMA were compared to WGS diagnostic and non-diagnostic results. Activities were costed in 2016 Canadian dollars (CDN). Ongoing care accounted for 88.6% of post-test activities. The mean number of lab tests was greater following CMA than WGS (0.55 vs. 0.09; p = 0.007). The mean number of specialist visits was greater following WGS than CMA (0.41 vs. 0; p = 0.016). WGS results (diagnostic vs. non-diagnostic) modified the effect of test type on mean number of activities (p textless 0.001). The cost of activities prompted by diagnostic WGS exceeded $557CDN for 10% of cases. In complex pediatric care, CMA prompted additional diagnostic investigations while WGS prompted tailored care guided by genotypic variants. Costs for prompted activities were low for the majority and constitute a small proportion of total test costs. Optimal use of WGS depends on robust evaluation of downstream care and cost consequences.},

note = {Number: 12 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{mahmood_methyl_2017,

title = {Methyl donor S-adenosylmethionine (SAM) supplementation attenuates breast cancer growth, invasion, and metastasis in vivo ; therapeutic and chemopreventive applications},

author = {Niaz Mahmood and David Cheishvili and Ani Arakelian and Imrana Tanvir and Haseeb Ahmed Khan and Anne-Sophie Pépin and Moshe Szyf and Shafaat A Rabbani},

url = {https://www.oncotarget.com/article/23704/text/},

doi = {10.18632/oncotarget.23704},

issn = {1949-2553},

year  = {2017},

date = {2017-01-01},

urldate = {2021-05-19},

journal = {Oncotarget},

volume = {9},

number = {4},

pages = {5169--5183},

abstract = {https://doi.org/10.18632/oncotarget.23704 Niaz Mahmood, David Cheishvili, Ani Arakelian, Imrana Tanvir, Haseeb Ahmed Khan, Anne-Sophie Pépin, Moshe Szyf, Shafaat A. Rabbani},

note = {Publisher: Impact Journals},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28126036b,

title = {Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types},

author = {Simone Ecker and Lu Chen and Vera Pancaldi and Frederik O Bagger and José María Fernández and Enrique Carrillo de Santa Pau and David Juan and Alice L Mann and Stephen Watt and Francesco Paolo Casale and Nikos Sidiropoulos and Nicolas Rapin and Angelika Merkel and  and Hendrik G Stunnenberg and Oliver Stegle and Mattia Frontini and Kate Downes and Tomi Pastinen and Taco W Kuijpers and Daniel Rico and Alfonso Valencia and Stephan Beck and Nicole Soranzo and Dirk S Paul},

doi = {10.1186/s13059-017-1156-8},

issn = {1474-760X},

year  = {2017},

date = {2017-01-01},

journal = {Genome Biol},

volume = {18},

number = {1},

pages = {18},

abstract = {BACKGROUND: A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability.



RESULTS: We apply a novel analytical approach to measure and compare transcriptional and epigenetic variability genome-wide across CD14CD16 monocytes, CD66bCD16 neutrophils, and CD4CD45RA naïve T cells from the same 125 healthy individuals. We discover substantially increased variability in neutrophils compared to monocytes and T cells. In neutrophils, genes with hypervariable expression are found to be implicated in key immune pathways and are associated with cellular properties and environmental exposure. We also observe increased sex-specific gene expression differences in neutrophils. Neutrophil-specific DNA methylation hypervariable sites are enriched at dynamic chromatin regions and active enhancers.



CONCLUSIONS: Our data highlight the importance of transcriptional and epigenetic variability for the key role of neutrophils as the first responders to inflammatory stimuli. We provide a resource to enable further functional studies into the plasticity of immune cells, which can be accessed from: http://blueprint-dev.bioinfo.cnio.es/WP10/hypervariability .},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27960086b,

title = {Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors},

author = {Jonathon Torchia and Brian Golbourn and Shengrui Feng and King Ching Ho and Patrick Sin-Chan and Alexandre Vasiljevic and Joseph D Norman and Paul Guilhamon and Livia Garzia and Natalia R Agamez and Mei Lu and Tiffany S Chan and Daniel Picard and Pasqualino de Antonellis and Dong-Anh Khuong-Quang and Aline C Planello and Constanze Zeller and Dalia Barsyte-Lovejoy and Lucie Lafay-Cousin and Louis Letourneau and Mathieu Bourgey and Man Yu and Deena M A Gendoo and Misko Dzamba and Mark Barszczyk and Tiago Medina and Alexandra N Riemenschneider and A Sorana Morrissy and Young-Shin Ra and Vijay Ramaswamy and Marc Remke and Christopher P Dunham and Stephen Yip and Ho-Keung Ng and Jian-Qiang Lu and Vivek Mehta and Steffen Albrecht and Jose Pimentel and Jennifer A Chan and Gino R Somers and Claudia C Faria and Lucia Roque and Maryam Fouladi and Lindsey M Hoffman and Andrew S Moore and Yin Wang and Seung Ah Choi and Jordan R Hansford and Daniel Catchpoole and Diane K Birks and Nicholas K Foreman and Doug Strother and Almos Klekner and Laszló Bognár and Miklós Garami and Péter Hauser and Tibor Hortobágyi and Beverly Wilson and Juliette Hukin and Anne-Sophie Carret and Timothy E Van Meter and Eugene I Hwang and Amar Gajjar and Shih-Hwa Chiou and Hideo Nakamura and Helen Toledano and Iris Fried and Daniel Fults and Takafumi Wataya and Chris Fryer and David D Eisenstat and Katrin Scheinemann and Adam J Fleming and Donna L Johnston and Jean Michaud and Shayna Zelcer and Robert Hammond and Samina Afzal and David A Ramsay and Nongnuch Sirachainan and Suradej Hongeng and Noppadol Larbcharoensub and Richard G Grundy and Rishi R Lulla and Jason R Fangusaro and Harriet Druker and Ute Bartels and Ronald Grant and David Malkin and C Jane McGlade and Theodore Nicolaides and Tarik Tihan and Joanna Phillips and Jacek Majewski and Alexandre Montpetit and Guillaume Bourque and Gary D Bader and Alyssa T Reddy and G Yancey Gillespie and Monika Warmuth-Metz and Stefan Rutkowski and Uri Tabori and Mathieu Lupien and Michael Brudno and Ulrich Schüller and Torsten Pietsch and Alexander R Judkins and Cynthia E Hawkins and Eric Bouffet and Seung-Ki Kim and Peter B Dirks and Michael D Taylor and Anat Erdreich-Epstein and Cheryl H Arrowsmith and Daniel D De Carvalho and James T Rutka and Nada Jabado and Annie Huang},

doi = {10.1016/j.ccell.2016.11.003},

issn = {1878-3686},

year  = {2016},

date = {2016-12-01},

journal = {Cancer Cell},

volume = {30},

number = {6},

pages = {891--908},

abstract = {We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27898055,

title = {Increased DNA methylation variability in type 1 diabetes across three immune effector cell types},

author = {Dirk S Paul and Andrew E Teschendorff and Mary A N Dang and Robert Lowe and Mohammed I Hawa and Simone Ecker and Huriya Beyan and Stephanie Cunningham and Alexandra R Fouts and Anita Ramelius and Frances Burden and Samantha Farrow and Sophia Rowlston and Karola Rehnstrom and Mattia Frontini and Kate Downes and Stephan Busche and Warren A Cheung and Bing Ge and Marie-Michelle Simon and David Bujold and Tony Kwan and Guillaume Bourque and Avik Datta and Ernesto Lowy and Laura Clarke and Paul Flicek and Emanuele Libertini and Simon Heath and Marta Gut and Ivo G Gut and Willem H Ouwehand and Tomi Pastinen and Nicole Soranzo and Sabine E Hofer and Beate Karges and Thomas Meissner and Bernhard O Boehm and Corrado Cilio and Helena Elding Larsson and Åke Lernmark and Andrea K Steck and Vardhman K Rakyan and Stephan Beck and R David Leslie},

doi = {10.1038/ncomms13555},

issn = {2041-1723},

year  = {2016},

date = {2016-11-01},

journal = {Nat Commun},

volume = {7},

pages = {13555},

abstract = {The incidence of type 1 diabetes (T1D) has substantially increased over the past decade, suggesting a role for non-genetic factors such as epigenetic mechanisms in disease development. Here we present an epigenome-wide association study across 406,365 CpGs in 52 monozygotic twin pairs discordant for T1D in three immune effector cell types. We observe a substantial enrichment of differentially variable CpG positions (DVPs) in T1D twins when compared with their healthy co-twins and when compared with healthy, unrelated individuals. These T1D-associated DVPs are found to be temporally stable and enriched at gene regulatory elements. Integration with cell type-specific gene regulatory circuits highlight pathways involved in immune cell metabolism and the cell cycle, including mTOR signalling. Evidence from cord blood of newborns who progress to overt T1D suggests that the DVPs likely emerge after birth. Our findings, based on 772 methylomes, implicate epigenetic changes that could contribute to disease pathogenesis in T1D.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27863956,

title = {The International Human Epigenome Consortium Data Portal},

author = {David Bujold and David Anderson de Lima Morais and Carol Gauthier and Catherine Côté and Maxime Caron and Tony Kwan and Kuang Chung Chen and Jonathan Laperle and Alexei Nordell Markovits and Tomi Pastinen and Bryan Caron and Alain Veilleux and Pierre-Étienne Jacques and Guillaume Bourque},

doi = {10.1016/j.cels.2016.10.019},

issn = {2405-4712},

year  = {2016},

date = {2016-11-01},

journal = {Cell Syst},

volume = {3},

number = {5},

pages = {496--499.e2},

abstract = {The International Human Epigenome Consortium (IHEC) coordinates the production of reference epigenome maps through the characterization of the regulome, methylome, and transcriptome from a wide range of tissues and cell types. To define conventions ensuring the compatibility of datasets and establish an infrastructure enabling data integration, analysis, and sharing, we developed the IHEC Data Portal (http://epigenomesportal.ca/ihec). The portal provides access to >7,000 reference epigenomic datasets, generated from >600 tissues, which have been contributed by seven international consortia: ENCODE, NIH Roadmap, CEEHRC, Blueprint, DEEP, AMED-CREST, and KNIH. The portal enhances the utility of these reference maps by facilitating the discovery, visualization, analysis, download, and sharing of epigenomics data. The IHEC Data Portal is the official source to navigate through IHEC datasets and represents a strategy for unifying the distributed data produced by international research consortia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27863252,

title = {The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease},

author = {William J Astle and Heather Elding and Tao Jiang and Dave Allen and Dace Ruklisa and Alice L Mann and Daniel Mead and Heleen Bouman and Fernando Riveros-Mckay and Myrto A Kostadima and John J Lambourne and Suthesh Sivapalaratnam and Kate Downes and Kousik Kundu and Lorenzo Bomba and Kim Berentsen and John R Bradley and Louise C Daugherty and Olivier Delaneau and Kathleen Freson and Stephen F Garner and Luigi Grassi and Jose Guerrero and Matthias Haimel and Eva M Janssen-Megens and Anita Kaan and Mihir Kamat and Bowon Kim and Amit Mandoli and Jonathan Marchini and Joost H A Martens and Stuart Meacham and Karyn Megy and Jared O'Connell and Romina Petersen and Nilofar Sharifi and Simon M Sheard and James R Staley and Salih Tuna and Martijn van der Ent and Klaudia Walter and Shuang-Yin Wang and Eleanor Wheeler and Steven P Wilder and Valentina Iotchkova and Carmel Moore and Jennifer Sambrook and Hendrik G Stunnenberg and Emanuele Di Angelantonio and Stephen Kaptoge and Taco W Kuijpers and Enrique Carrillo-de-Santa-Pau and David Juan and Daniel Rico and Alfonso Valencia and Lu Chen and Bing Ge and Louella Vasquez and Tony Kwan and Diego Garrido-Martín and Stephen Watt and Ying Yang and Roderic Guigo and Stephan Beck and Dirk S Paul and Tomi Pastinen and David Bujold and Guillaume Bourque and Mattia Frontini and John Danesh and David J Roberts and Willem H Ouwehand and Adam S Butterworth and Nicole Soranzo},

doi = {10.1016/j.cell.2016.10.042},

issn = {1097-4172},

year  = {2016},

date = {2016-11-01},

journal = {Cell},

volume = {167},

number = {5},

pages = {1415--1429.e19},

abstract = {Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27863251,

title = {Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells},

author = {Lu Chen and Bing Ge and Francesco Paolo Casale and Louella Vasquez and Tony Kwan and Diego Garrido-Martín and Stephen Watt and Ying Yan and Kousik Kundu and Simone Ecker and Avik Datta and David Richardson and Frances Burden and Daniel Mead and Alice L Mann and Jose Maria Fernandez and Sophia Rowlston and Steven P Wilder and Samantha Farrow and Xiaojian Shao and John J Lambourne and Adriana Redensek and Cornelis A Albers and Vyacheslav Amstislavskiy and Sofie Ashford and Kim Berentsen and Lorenzo Bomba and Guillaume Bourque and David Bujold and Stephan Busche and Maxime Caron and Shu-Huang Chen and Warren Cheung and Oliver Delaneau and Emmanouil T Dermitzakis and Heather Elding and Irina Colgiu and Frederik O Bagger and Paul Flicek and Ehsan Habibi and Valentina Iotchkova and Eva Janssen-Megens and Bowon Kim and Hans Lehrach and Ernesto Lowy and Amit Mandoli and Filomena Matarese and Matthew T Maurano and John A Morris and Vera Pancaldi and Farzin Pourfarzad and Karola Rehnstrom and Augusto Rendon and Thomas Risch and Nilofar Sharifi and Marie-Michelle Simon and Marc Sultan and Alfonso Valencia and Klaudia Walter and Shuang-Yin Wang and Mattia Frontini and Stylianos E Antonarakis and Laura Clarke and Marie-Laure Yaspo and Stephan Beck and Roderic Guigo and Daniel Rico and Joost H A Martens and Willem H Ouwehand and Taco W Kuijpers and Dirk S Paul and Hendrik G Stunnenberg and Oliver Stegle and Kate Downes and Tomi Pastinen and Nicole Soranzo},

doi = {10.1016/j.cell.2016.10.026},

issn = {1097-4172},

year  = {2016},

date = {2016-11-01},

journal = {Cell},

volume = {167},

number = {5},

pages = {1398--1414.e24},

abstract = {Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in three major human immune cell types (CD14 monocytes, CD16 neutrophils, and naive CD4 T cells) from up to 197 individuals. We assess, quantitatively, the relative contribution of cis-genetic and epigenetic factors to transcription and evaluate their impact as potential sources of confounding in epigenome-wide association studies. Further, we characterize highly coordinated genetic effects on gene expression, methylation, and histone variation through quantitative trait locus (QTL) mapping and allele-specific (AS) analyses. Finally, we demonstrate colocalization of molecular trait QTLs at 345 unique immune disease loci. This expansive, high-resolution atlas of multi-omics changes yields insights into cell-type-specific correlation between diverse genomic inputs, more generalizable correlations between these inputs, and defines molecular events that may underpin complex disease risk.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}