Publications

@article{sanchez-ferras_coordinated_2021,

title = {A coordinated progression of progenitor cell states initiates urinary tract development},

author = {Oraly Sanchez-Ferras and Alain Pacis and Maria Sotiropoulou and Yuhong Zhang and Yu Chang Wang and Mathieu Bourgey and Guillaume Bourque and Jiannis Ragoussis and Maxime Bouchard},

url = {https://www.nature.com/articles/s41467-021-22931-5},

doi = {10.1038/s41467-021-22931-5},

issn = {2041-1723},

year  = {2021},

date = {2021-01-01},

urldate = {2021-05-12},

journal = {Nature Communications},

volume = {12},

number = {1},

pages = {2627},

abstract = {The kidney and upper urinary tract develop through reciprocal interactions between the ureteric bud and the surrounding mesenchyme. Ureteric bud branching forms the arborized collecting duct system of the kidney, while ureteric tips promote nephron formation from dedicated progenitor cells. While nephron progenitor cells are relatively well characterized, the origin of ureteric bud progenitors has received little attention so far. It is well established that the ureteric bud is induced from the nephric duct, an epithelial duct derived from the intermediate mesoderm of the embryo. However, the cell state transitions underlying the progression from intermediate mesoderm to nephric duct and ureteric bud remain unknown. Here we show that nephric duct morphogenesis results from the coordinated organization of four major progenitor cell populations. Using single cell RNA-seq and Cluster RNA-seq, we show that these progenitors emerge in time and space according to a stereotypical pattern. We identify the transcription factors Tfap2a/b and Gata3 as critical coordinators of this progenitor cell progression. This study provides a better understanding of the cellular origin of the renal collecting duct system and associated urinary tract developmental diseases, which may inform guided differentiation of functional kidney tissue.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {C3G, genomics, RNA-seq},

pubstate = {published},

tppubtype = {article}

}

@article{ward_white_2021,

title = {White pupae phenotype of tephritids is caused by parallel mutations of a MFS transporter},

author = {Christopher M Ward and Roswitha A Aumann and Mark A Whitehead and Katerina Nikolouli and Gary Leveque and Georgia Gouvi and Elisabeth Fung and Sarah J Reiling and Haig Djambazian and Margaret A Hughes and Sam Whiteford and Carlos Caceres-Barrios and Thu N M Nguyen and Amanda Choo and Peter Crisp and Sheina B Sim and Scott M Geib and František Marec and Irina Häcker and Jiannis Ragoussis and Alistair C Darby and Kostas Bourtzis and Simon W Baxter and Marc F Schetelig},

url = {https://www.nature.com/articles/s41467-020-20680-5},

doi = {10.1038/s41467-020-20680-5},

issn = {2041-1723},

year  = {2021},

date = {2021-01-01},

urldate = {2021-05-28},

journal = {Nature Communications},

volume = {12},

number = {1},

pages = {491},

abstract = {Mass releases of sterilized male insects, in the frame of sterile insect technique programs, have helped suppress insect pest populations since the 1950s. In the major horticultural pests Bactrocera dorsalis, Ceratitis capitata, and Zeugodacus cucurbitae, a key phenotype white pupae (wp) has been used for decades to selectively remove females before releases, yet the gene responsible remained unknown. Here, we use classical and modern genetic approaches to identify and functionally characterize causal wp− mutations in these distantly related fruit fly species. We find that the wp phenotype is produced by parallel mutations in a single, conserved gene. CRISPR/Cas9-mediated knockout of the wp gene leads to the rapid generation of white pupae strains in C. capitata and B. tryoni. The conserved phenotype and independent nature of wp− mutations suggest this technique can provide a generic approach to produce sexing strains in other major medical and agricultural insect pests.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lee_reference_2021,

title = {Reference genome assembly for Australian Ascochyta lentis isolate Al4},

author = {Robert C Lee and Lina Farfan-Caceres and Johannes W Debler and Angela H Williams and Robert A Syme and Bernadette M Henares},

url = {https://doi.org/10.1093/g3journal/jkab006},

doi = {10.1093/g3journal/jkab006},

issn = {2160-1836},

year  = {2021},

date = {2021-01-01},

urldate = {2021-05-28},

journal = {G3 GenestextbarGenomestextbarGenetics},

volume = {11},

number = {jkab006},

abstract = {Ascochyta lentis causes ascochyta blight in lentil (Lens culinaris Medik.) and yield loss can be as high as 50%. With careful agronomic management practices, fungicide use, and advances in breeding resistant lentil varieties, disease severity and impact to farmers have been largely controlled. However, evidence from major lentil producing countries, Canada and Australia, suggests that A. lentis isolates can change their virulence profile and level of aggressiveness over time and under different selection pressures. In this paper, we describe the first genome assembly for A. lentis for the Australian isolate Al4, through the integration of data from Illumina and PacBio SMRT sequencing. The Al4 reference genome assembly is almost 42 Mb in size and encodes 11,638 predicted genes. The Al4 genome comprises 21 full-length and gapless chromosomal contigs and two partial chromosome contigs each with one telomere. We predicted 31 secondary metabolite clusters, and 38 putative protein effectors, many of which were classified as having an unknown function. Comparison of A. lentis genome features with the recently published reference assembly for closely related A. rabiei show that genome synteny between these species is highly conserved. However, there are several translocations and inversions of genome sequence. The location of secondary metabolite clusters near transposable element and repeat-rich genomic regions was common for A. lentis as has been reported for other fungal plant pathogens.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{dursi_candig_2021,

title = {CanDIG: Secure Federated Genomic Queries and Analyses Across Jurisdictions},

author = {Jonathan L Dursi and Zoltan Bozoky and Richard de Borja and Jimmy Li and David Bujold and Adam Lipski and Shaikh Farhan Rashid and Amanjeev Sethi and Neelam Memon and Dashaylan Naidoo and Felipe Coral-Sasso and Matthew Wong and P -O Quirion and Zhibin Lu and Samarth Agarwal and Kat Pavlov and Andrew Ponomarev and Mia Husic and Krista Pace and Samantha L Palmer and Stephanie A Grover and Sevan Hakgor and Lillian L Siu and David Malkin and Carl Virtanen and Trevor J Pugh and Pierre-Étienne Jacques and Yann Joly and Steven J M Jones and Guillaume Bourque and Michael Brudno},

url = {https://www.biorxiv.org/content/10.1101/2021.03.30.434101v1},

doi = {10.1101/2021.03.30.434101},

year  = {2021},

date = {2021-01-01},

urldate = {2021-05-28},

journal = {bioRxiv},

pages = {2021.03.30.434101},

abstract = {textlessh3textgreaterAbstracttextless/h3textgreater textlessptextgreaterRapid expansions of bioinformatics and computational biology have broadened the collection and use of -omics data including genomic, transcriptomic, methylomic and a myriad of other health data types, in the clinic and the laboratory. Both clinical and research uses of such data require co-analysis with large datasets, for which participant privacy and the need for data custodian controls must remain paramount. This is particularly challenging in multi-jurisdictional settings, such as Canada, where health privacy and security requirements are often heterogeneous. Data federation presents a solution to this, allowing for integration and analysis of large datasets from various sites while abiding by local policies.textless/ptextgreatertextlessptextgreaterThe Canadian Distributed Infrastructure for Genomics platform (CanDIG) enables federated querying and analysis of -omics and health data while keeping that data local and under local control. It builds upon existing infrastructures to connect five health and research institutions across Canada, relies heavily on standards and tooling brought together by the Global Alliance for Genomics and Health (GA4GH), implements a clear division of responsibilities among its participants and adheres to international data sharing standards. Participating researchers and clinicians can therefore contribute to and quickly access a critical mass of -omics data across a national network in a manner that takes into account the multi-jurisdictional nature of our privacy and security policies. Through this, CanDIG gives medical and research communities the tools needed to use and analyze the ever-growing amount of -omics data available to them in order to improve our understanding and treatment of various conditions and diseases. CanDIG is being used to make genomic and phenotypic data available for querying across Canada as part of data sharing for five leading pan-Canadian projects including the Terry Fox Comprehensive Cancer Care Centre Consortium Network (TF4CN) and Terry Fox PRecision Oncology For Young peopLE (PROFYLE), and making data from provincial projects such as POG (Personalized Onco- Genomics) more widely available.textless/ptextgreater},

note = {Publisher: Cold Spring Harbor Laboratory 

Section: New Results},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lopezleyva_human_2021b,

title = {Human Milk Microbiota in an Indigenous Population Is Associated with Maternal Factors, Stage of Lactation, and Breastfeeding Practices},

author = {Lilian Lopez Leyva and Emmanuel Gonzalez and Chen Li and Tamara Ajeeb and Noel W Solomons and Luis B Agellon and Marilyn E Scott and Kristine G Koski},

url = {https://doi.org/10.1093/cdn/nzab013},

doi = {10.1093/cdn/nzab013},

issn = {2475-2991},

year  = {2021},

date = {2021-01-01},

urldate = {2021-05-28},

journal = {Current Developments in Nutrition},

volume = {5},

number = {nzab013},

abstract = {Human milk contains a diverse community of bacteria that are modified by maternal factors, but whether these or other factors are similar in developing countries has not been explored. Our objective was to determine whether the milk microbiota was modified by maternal age, BMI, parity, lactation stage, subclinical mastitis (SCM), and breastfeeding practices in the first 6 mo of lactation in an indigenous population from Guatemala.For this cross-sectional study, Mam-Mayan indigenous mothers nursing infants aged <6 mo were recruited. Unilateral human milk samples were collected (n = 86) and processed for 16S rRNA sequencing at the genus level. Microbial diversity and relative abundance were compared with maternal factors [age, BMI, parity, stage of lactation, SCM, and 3 breastfeeding practices (exclusive, predominant, mixed)] obtained through questionnaires.Streptococcus was the most abundant genus (33.8%), followed by Pseudomonas (18.7%) and Sphingobium (10.7%) but relative abundance was associated with maternal factors. First, Lactobacillus and Streptococcus were more abundant in early lactation whereas the common oral (Leptotrichia) and environmental (Comamonas) bacteria were more abundant in established lactation. Second, Streptococcus,Lactobacillus,Lactococcus,Leuconostoc, and Micrococcus had a higher abundance in multiparous mothers compared with primiparous mothers. Third, a more diverse microbiota characterized by a higher abundance of lactic acid bacteria (Lactobacillus,Leuconostoc, and Lactococcus), Leucobacter, and Micrococcus was found in mothers with a healthy BMI. Finally, distinct microbial communities differed by stage of lactation and by exclusive, predominant, or mixed breastfeeding practices.Milk bacterial communities in an indigenous community were associated with maternal factors. Higher microbial diversity was supported by having a healthy BMI, the absence of SCM, and by breastfeeding. Interestingly, breastfeeding practices when assessed by lactation stage were associated with distinct microbiota profiles.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{el-far_upregulated_2021,

title = {Upregulated IL-32 Expression And Reduced Gut Short Chain Fatty Acid Caproic Acid in People Living With HIV With Subclinical Atherosclerosis},

author = {Mohamed El-Far and Madeleine Durand and Isabelle Turcotte and Etienne Larouche-Anctil and Mohamed Sylla and Sarah Zaidan and Carl Chartrand-Lefebvre and Rémi Bunet and Hardik Ramani and Manel Sadouni and Irina Boldeanu and Annie Chamberland and Sylvie Lesage and Jean-Guy Baril and Benoit Trottier and Réjean Thomas and Emmanuel Gonzalez and Ali Filali-Mouhim and Jean-Philippe Goulet and Jeffrey A Martinson and Seble Kassaye and Roksana Karim and Jorge R Kizer and Audrey L French and Stephen J Gange and Petronela Ancuta and Jean-Pierre Routy and David B Hanna and Robert C Kaplan and Nicolas Chomont and Alan L Landay and Cécile L Tremblay},

url = {https://www.frontiersin.org/articles/10.3389/fimmu.2021.664371/full},

doi = {10.3389/fimmu.2021.664371},

issn = {1664-3224},

year  = {2021},

date = {2021-01-01},

urldate = {2021-05-28},

journal = {Frontiers in Immunology},

volume = {12},

abstract = {Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) are still at higher risk for cardiovascular diseases (CVDs) that are mediated by chronic inflammation. Identification of novel inflammatory mediators with the inherent potential to be used as CVD biomarkers and also as therapeutic targets is critically needed for better risk stratification and disease management in PLWH. Here, we investigated the expression and potential role of the multi-isoform proinflammatory cytokine IL-32 in subclinical atherosclerosis in PLWH (n=49 with subclinical atherosclerosis and n=30 without) and HIV- controls (n=25 with subclinical atherosclerosis and n=24 without). While expression of all tested IL-32 isoforms (α, β, γ, D, ε, and θ) was significantly higher in peripheral blood from PLWH compared to HIV- controls, IL-32D and IL-32θ isoforms were further upregulated in HIV+ individuals with coronary artery atherosclerosis compared to their counterparts without. Upregulation of these two isoforms was associated with increased plasma levels of IL-18 and IL-1β and downregulation of the atheroprotective protein TRAIL, which together composed a unique atherosclerotic inflammatory signature specific for PLWH compared to HIV- controls. Logistic regression analysis demonstrated that modulation of these inflammatory variables was independent of age, smoking, and statin treatment. Furthermore, our in vitro functional data linked IL-32 to macrophage activation and production of IL-18 and downregulation of TRAIL, a mechanism previously shown to be associated with impaired cholesterol metabolism and atherosclerosis. Finally, increased expression of IL-32 isoforms in PLWH with subclinical atherosclerosis was associated with altered gut microbiome (increased pathogenic bacteria; Rothia and Eggerthella species) and lower abundance of the gut metabolite short-chain fatty acid (SCFA) caproic acid, measured in fecal samples from the study participants. Importantly, caproic acid diminished the production of IL-32, IL-18, and IL-1β in human PBMCs in response to bacterial LPS stimulation. In conclusion, our studies identified an HIV-specific atherosclerotic inflammatory signature including specific IL-32 isoforms, which is regulated by the SCFA caproic acid and that may lead to new potential therapies to prevent CVD in ART-treated PLWH.},

note = {Publisher: Frontiers},

keywords = {Atherosclerosis, CVD (cardio vascular disease), gut microbiome, HIV, IL-32, Inflammation, short-chain fatty acids},

pubstate = {published},

tppubtype = {article}

}

@article{brereton_reanalysis_2021,

title = {Reanalysis of the Mars500 experiment reveals common gut microbiome alterations in astronauts induced by long-duration confinement},

author = {N J B Brereton and F E Pitre and E Gonzalez},

url = {https://www.sciencedirect.com/science/article/pii/S2001037021001306},

doi = {10.1016/j.csbj.2021.03.040},

issn = {2001-0370},

year  = {2021},

date = {2021-01-01},

urldate = {2021-05-28},

journal = {Computational and Structural Biotechnology Journal},

volume = {19},

pages = {2223--2235},

abstract = {Maintaining astronaut health throughout long-duration spaceflight is essential to the feasibility of a manned mission to Mars. The ground-based Mars500 experiment investigated long-duration health by isolating six astronauts for 520 days, the longest controlled human confinement study conducted to date. After 520 days, astronauts had uniform strength and lean body mass losses, and increased fasting plasma glucose, calprotectin, and neutrophil levels characteristic of intestinal inflammation but previous analyses revealed no common significant changes in gut microbiota. This study reanalysed data from early (days 7–45) and late (days 420–520) faecal samples and identified 408 exact sequence variants (ESVs), including 213 shared by all astronauts. Thirty-two ESVs were significantly differentially abundant over time, including depletion of keystone resistant starch degrading, anti-inflammatory and insulin sensitivity-associated species, such as Faecalibacterium prausnitzii, Ruminococcus bromii, Blautia luti, Anaerostipes hadrus, Roseburia faecis, and Lactobacillus rogosae, and enrichment of yet-to-be-cultured bacteria. Additionally, the extraordinary experimental confinement allowed observation of microbiota potentially shared between astronauts and their habitat. Forty-nine species were shared, representing 49% and 12% of the human and environmental microbiome diversity, respectively. These findings reveal the microbiota which significantly altered in relative abundance throughout confinement, including species known to influence inflammation and host glucose homeostasis consistent with astronaut symptoms. Identification of microbiome alterations after 520 days of isolation represents a missing piece connecting Mars500 astronaut physiological studies. Knowledge of the impact of long-term confinement upon the human microbiome helps to improve our understanding of how humans interact with their habitats and is a valuable step forward towards enabling long-duration spaceflight.},

keywords = {16S rRNA gene, Astronaut health, Mars, Microbiome, Space science},

pubstate = {published},

tppubtype = {article}

}

@article{chehboun_point_2020b,

title = {A point mutation in the linker domain of mouse STAT5A is associated with impaired NK-cell regulation},

author = {Salma Chehboun and Gabriel André Leiva-Torres and Benoît Charbonneau and Robert Eveleigh and Guillaume Bourque and Silvia Marina Vidal},

url = {https://www.nature.com/articles/s41435-019-0088-6},

doi = {10.1038/s41435-019-0088-6},

issn = {1476-5470},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-26},

journal = {Genes & Immunity},

volume = {21},

number = {2},

pages = {136--141},

abstract = {The transcription factor STAT5 is critical for peripheral NK-cell survival, proliferation, and cytotoxic function. STAT5 refers to two highly related proteins, STAT5A and STAT5B. In this study, we verified the importance of STAT5A isoform for NK cells. We characterized an incidental chemically induced W484G mutation in the Stat5a gene and found that this mutation was associated with a reduction of STAT5A protein expression. Closer examination of NK-cell subsets from Stat5a mutant mice showed marked reductions in NK-cell number and maturation. IL-15 treatment of Stat5a mutant NK cells exhibited defective induction of both STAT5 and mTOR signaling pathways and reduced expression of granzyme B and IFN-γ. Finally, we observed that Stat5a mutant mice revealed more tumor growth upon injection of RMA-S tumor cell line. Overall, our results demonstrate that the W484G mutation in the linker domain of STAT5A is sufficient to compromise STAT5A function in NK-cell homeostasis, responsiveness, and tumoricidal function.},

note = {Number: 2 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{brereton_co-cropping_2020,

title = {Co-cropping with three phytoremediation crops influences rhizosphere microbiome community in contaminated soil},

author = {N J B Brereton and E Gonzalez and D Desjardins and M Labrecque and F E Pitre},

url = {https://www.sciencedirect.com/science/article/pii/S0048969719350594},

doi = {10.1016/j.scitotenv.2019.135067},

issn = {0048-9697},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-26},

journal = {Science of The Total Environment},

volume = {711},

pages = {135067},

abstract = {Human industrial activities have left millions of hectares of land polluted with trace element metals and persistent organic pollutants (POPs) around the world. Although contaminated sites are environmentally damaging, high economic costs often discourage soil remediation efforts. Phytoremediation is a potential green technology solution but can be challenging due to the diversity of anthropogenic contaminants. Co-cropping could provide improved tolerance to diverse soil challenges by taking advantage of distinct crop capabilities. Co-cropping of three species with potentially complementary functions, Festuca arundinacea, Salix miyabeana and Medicago sativa, perform well on diversely contaminated soils. Here, rhizosphere microbiomes of each crop in monoculture and in all co-cropping combinations were compared using 16S rRNA gene amplification, sequencing and differential abundance analysis. The hyperaccumulating F. arundinacea rhizosphere microbiome included putative plant growth promoting bacteria (PGPB) and metal tolerance species, such as Rhizorhapis suberifaciens, Cellvibrio fibrivorans and Pseudomonas lini. The rhizosphere microbiome of the fast-growing tree S. miyabeana included diverse taxa involved in POP degradation, including the species Phenylobacterium panacis. The well-characterised nitrogen-fixing M. sativa microbiome species, Sinorhizobium meliloti, was identified alongside others involved in nutrient acquisition and putative yet-to-be-cultured Candidatus saccharibacteria (TM7-1 group). The majority of differentially abundant rhizosphere-associated bacterial species were maintained in co-cropping pairs, with pairs having higher numbers of differentially abundant taxa than monocultures in all cases. This was not the case when all three crops were co-cropped, where most host-specific bacterial species were not detected as differentially abundant, indicating the potential for reduced rhizosphere functionality. The crops cultivated in pairs here retained rhizosphere microbiome bacteria involved in these monoculture ecosystem services of plant growth promotion, POP tolerance and degradation, and improved nutrient acquisition. These findings provide a promising outlook of the potential for complementary co-cropping strategies for phytoremediation of the multifaceted anthropogenic pollution which can disastrously affect soils around the world.},

keywords = {16S rRNA, Co-cropping, Metagenomics, Microbiome, Phytoremediation, Rhizosphere},

pubstate = {published},

tppubtype = {article}

}

@article{nikbakht_latency_2020,

title = {Latency and interval therapy affect the evolution in metastatic colorectal cancer},

author = {Hamid Nikbakht and Selin Jessa and Mahadeo A Sukhai and Madeleine Arseneault and Tong Zhang and Louis Letourneau and Mariam Thomas and Mathieu Bourgey and Michael H A Roehrl and Robert Eveleigh and Eric X Chen and Monika Krzyzanowska and Malcolm J Moore and Amanda Giesler and Celeste Yu and Philippe L Bedard and Suzanne Kamel-Reid and Jacek Majewski and Lillian L Siu and Yasser Riazalhosseini and Donna M Graham},

url = {https://www.nature.com/articles/s41598-020-57476-y},

doi = {10.1038/s41598-020-57476-y},

issn = {2045-2322},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-26},

journal = {Scientific Reports},

volume = {10},

number = {1},

pages = {581},

abstract = {While comparison of primary tumor and metastases has highlighted genomic heterogeneity in colorectal cancer (CRC), previous studies have focused on a single metastatic site or limited genomic testing. Combining data from whole exome and ultra-deep targeted sequencing, we explored possible evolutionary trajectories beyond the status of these mutations, particularly among patient-matched metastatic tumors. Our findings confirm the persistence of known clinically-relevant mutations (e.g., those of RAS family of oncogenes) in CRC primary and metastases, yet reveal that latency and interval systemic therapy affect the course of evolutionary events within metastatic lesions. Specifically, our analysis of patient-matched primary and multiple metastatic lesions, developed over time, showed a similar genetic composition for liver metastatic tumors, which were 21-months apart. This genetic makeup was different from those identified in lung metastases developed before manifestation of the second liver metastasis. These results underscore the role of latency in the evolutionary path of metastatic CRC and may have implications for future treatment options.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{,

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-26},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lee_characterization_2020,

title = {Characterization of Growth Morphology and Pathology, and Draft Genome Sequencing of Botrytis fabae, the Causal Organism of Chocolate Spot of Faba Bean (Vicia faba L.)},

author = {Robert C Lee and Lina M Farfan-Caceres and Johannes W Debler and Robert A Syme},

url = {https://www.frontiersin.org/articles/10.3389/fmicb.2020.00217/full},

doi = {10.3389/fmicb.2020.00217},

issn = {1664-302X},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-26},

journal = {Frontiers in Microbiology},

volume = {11},

abstract = {Abstract Chocolate spot is a major fungal disease of faba bean caused by the ascomycete fungus, Botrytis fabae. B. fabae is also implicated in botrytis grey mould disease in lentils, along with B. cinerea. Here we have isolated and characterised two B. fabae isolates from chocolate spot lesions on faba bean leaves. In plant disease assays on faba bean and lentil, B. fabae was more aggressive than B. cinerea and we observed variation in susceptibility among a small set of cultivars for both plant hosts. Using light microscopy, we observed a spreading, generalised necrosis response in faba bean towards B. fabae. In contrast, the plant response to B. cinerea was localised to epidermal cells underlying germinated spores and appressoria. In addition to the species characterisation of B. fabae, we produced genome assemblies for both B. fabae isolates using Illumina sequencing. Genome sequencing coverage and assembly size for B. fabae isolates, were 27x and 45x, and 43.2 Mb and 44.5 Mb, respectively. Following genome assembly and annotation, carbohydrate-active enzyme (CAZymes) and effector genes were predicted. There were no major differences in the numbers of each of the major classes of CAZymes. We predicted 29 effector genes for B. fabae, and using the same selection criteria for B. cinerea, we predicted 34 putative effector genes. For five of the predicted effector genes, the pairwise dN/dS ratio between orthologs from B. fabae and B. cinerea was greater than 1.0, suggesting positive selection and the potential evolution of molecular mechanisms for host specificity in B. fabae. Furthermore, a homology search of secondary metabolite clusters revealed the absence of the B. cinerea phytotoxin botrydial and several other uncharacterised secondary metabolite biosynthesis genes from B. fabae. Although there were no obvious differences in the number or proportional representation of different transposable element classes, the overall proportion of AT-rich DNA sequence in B. fabae was double that of B. cinerea.},

note = {Publisher: Frontiers},

keywords = {ascomycete, BGM, botrytis fabae, chocolate spot, faba bean, Grey mould, Lens culinaris, Lentil, Necrotroph, phytopathogen, Plant Pathogen, Vicia faba},

pubstate = {published},

tppubtype = {article}

}

@article{morfin_interaction_2020,

title = {Interaction of field realistic doses of clothianidin and Varroa destructor parasitism on adult honey bee (Apis mellifera L.) health and neural gene expression, and antagonistic effects on differentially expressed genes},

author = {Nuria Morfin and Paul H Goodwin and Ernesto Guzman-Novoa},

url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229030},

doi = {10.1371/journal.pone.0229030},

issn = {1932-6203},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-26},

journal = {PLOS ONE},

volume = {15},

number = {2},

pages = {e0229030},

abstract = {While many studies have examined the effects of neonicotinoid insecticides and the parasitic mite Varroa destructor on honey bees (Apis mellifera), more information on the combined effects of such stressors on gene expression, including neural related genes, and their impact on biological pathways is needed. This study analyzed the effects of field realistic concentrations of the neonicotinoid clothianidin on adult bees infested and not infested with V. destructor over 21 consecutive days and then determined bee survivorship, weight, deformed wing virus (DWV) levels and gene expression. V. destructor parasitism with or without clothianidin exposure was significantly associated with decreased survivorship, weight loss and higher DWV levels, while clothianidin exposure was only associated with higher levels of DWV. Expression analysis of the neural genes AmNlg-1, BlCh and AmAChE-2 showed that V. destructor caused a significant down-regulation of all of them, whereas clothianidin caused a significant down-regulation of only AmNrx-1 and BlCh. An interaction was only detected for AmNrx-1 expression. RNAseq analysis showed that clothianidin exposure resulted in 6.5 times more up-regulated differentially expressed genes (DEGs) than V. destructor alone and 123 times more than clothianidin combined with V. destructor. Similar results were obtained with down-regulated DEGs, except for a higher number of DEGs shared between V. destructor and the combined stressors. KEGG (Kyoto Encyclopedia of Genes and Genomes) biological pathway analysis of the DEGs showed that the stressor linked to the highest number of KEGG pathways was clothianidin, followed by V. destructor, and then considerably fewer number of KEGG pathways with the combined stressors. The reduced numbers of DEGs and KEGG pathways associated with the DEGs for the combined stressors compared to the stressors alone indicates that the interaction of the stressors is not additive or synergistic, but antagonistic. The possible implications of the antagonistic effect on the number of DEGs are discussed.},

note = {Publisher: Public Library of Science},

keywords = {Bees, Behavior, Gene expression, Honey bees, Insecticides, Invertebrate genomics, Mites, Parasitism},

pubstate = {published},

tppubtype = {article}

}

@article{el-sehemy_norrin_2020,

title = {Norrin mediates tumor-promoting and -suppressive effects in glioblastoma via Notch and Wnt},

author = {Ahmed El-Sehemy and Hayden Selvadurai and Arturo Ortin-Martinez and Neno Pokrajac and Yasin Mamatjan and Nobuhiko Tachibana and Katherine Rowland and Lilian Lee and Nicole Park and Kenneth Aldape and Peter Dirks and Valerie A Wallace},

url = {https://www.jci.org/articles/view/128994},

doi = {10.1172/JCI128994},

issn = {0021-9738},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-26},

journal = {The Journal of Clinical Investigation},

volume = {130},

number = {6},

pages = {3069--3086},

note = {Publisher: American Society for Clinical Investigation},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{moolhuijzen_expansion_2020,

title = {Expansion and Conservation of Biosynthetic Gene Clusters in Pathogenic Pyrenophora spp.},

author = {Paula M Moolhuijzen and Mariano Jordi Muria-Gonzalez and Robert Syme and Catherine Rawlinson and Pao Theen See and Caroline S Moffat and Simon R Ellwood},

url = {https://www.mdpi.com/2072-6651/12/4/242},

doi = {10.3390/toxins12040242},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-26},

journal = {Toxins},

volume = {12},

number = {4},

pages = {242},

abstract = {Pyrenophora is a fungal genus responsible for a number of major cereal diseases. Although fungi produce many specialised or secondary metabolites for defence and interacting with the surrounding environment, the repertoire of specialised metabolites (SM) within Pyrenophora pathogenic species remains mostly uncharted. In this study, an in-depth comparative analysis of the P. teres f. teres, P teres f. maculata and P. tritici-repentis potential to produce SMs, based on in silico predicted biosynthetic gene clusters (BGCs), was conducted using genome assemblies from PacBio DNA reads. Conservation of BGCs between the Pyrenophora species included type I polyketide synthases, terpene synthases and the first reporting of a type III polyketide synthase in P teres f. maculata. P. teres isolates exhibited substantial expansion of non-ribosomal peptide synthases relative to P. tritici-repentis, hallmarked by the presence of tailoring cis-acting nitrogen methyltransferase domains. P. teres isolates also possessed unique non-ribosomal peptide synthase (NRPS)-indole and indole BGCs, while a P. tritici-repentis phytotoxin BGC for triticone production was absent in P. teres. These differences highlight diversification between the pathogens that reflects their different evolutionary histories, host adaption and lifestyles.},

note = {Number: 4 

Publisher: Multidisciplinary Digital Publishing Institute},

keywords = {comparative genomics, necrotrophic fungal pathogen, NRPS, PKS, secondary metabolism, synteny},

pubstate = {published},

tppubtype = {article}

}

@article{choufani_dna_2020,

title = {DNA Methylation Signature for EZH2 Functionally Classifies Sequence Variants in Three PRC2 Complex Genes},

author = {Sanaa Choufani and William T Gibson and Andrei L Turinsky and Brian H Y Chung and Tianren Wang and Kopal Garg and Alessandro Vitriolo and Ana S A Cohen and Sharri Cyrus and Sarah Goodman and Eric Chater-Diehl and Jack Brzezinski and Michael Brudno and Luk Ho Ming and Susan M White and Sally Ann Lynch and Carol Clericuzio and Karen I Temple and Frances Flinter and Vivienne McConnell and Tom Cushing and Lynne M Bird and Miranda Splitt and Bronwyn Kerr and Stephen W Scherer and Jerry Machado and Eri Imagawa and Nobuhiko Okamoto and Naomichi Matsumoto and Guiseppe Testa and Maria Iascone and Romano Tenconi and Oana Caluseriu and Roberto Mendoza-Londono and David Chitayat and Cheryl Cytrynbaum and Katrina Tatton-Brown and Rosanna Weksberg},

url = {https://www.cell.com/ajhg/abstract/S0002-9297(20)30084-7},

doi = {10.1016/j.ajhg.2020.03.008},

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

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-26},

journal = {The American Journal of Human Genetics},

volume = {106},

number = {5},

pages = {596--610},

note = {Publisher: Elsevier},

keywords = {DNA methylation signature, EED, intellectual disability, overgrowth syndromes, SUZ12},

pubstate = {published},

tppubtype = {article}

}

@article{caron_single-cell_2020,

title = {Single-cell analysis of childhood leukemia reveals a link between developmental states and ribosomal protein expression as a source of intra-individual heterogeneity},

author = {Maxime Caron and Pascal St-Onge and Thomas Sontag and Yu Chang Wang and Chantal Richer and Ioannis Ragoussis and Daniel Sinnett and Guillaume Bourque},

url = {https://www.nature.com/articles/s41598-020-64929-x},

doi = {10.1038/s41598-020-64929-x},

issn = {2045-2322},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-26},

journal = {Scientific Reports},

volume = {10},

number = {1},

pages = {8079},

abstract = {Childhood acute lymphoblastic leukemia (cALL) is the most common pediatric cancer. It is characterized by bone marrow lymphoid precursors that acquire genetic alterations, resulting in disrupted maturation and uncontrollable proliferation. More than a dozen molecular subtypes of variable severity can be used to classify cALL cases. Modern therapy protocols currently cure 85–90% of cases, but other patients are refractory or will relapse and eventually succumb to their disease. To better understand intratumor heterogeneity in cALL patients, we investigated the nature and extent of transcriptional heterogeneity at the cellular level by sequencing the transcriptomes of 39,375 individual cells in eight patients (six B-ALL and two T-ALL) and three healthy pediatric controls. We observed intra-individual transcriptional clusters in five out of the eight patients. Using pseudotime maturation trajectories of healthy B and T cells, we obtained the predicted developmental state of each leukemia cell and observed distribution shifts within patients. We showed that the predicted developmental states of these cancer cells are inversely correlated with ribosomal protein expression levels, which could be a common contributor to intra-individual heterogeneity in cALL patients.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{groza_personalized_2020,

title = {Personalized and graph genomes reveal missing signal in epigenomic data},

author = {Cristian Groza and Tony Kwan and Nicole Soranzo and Tomi Pastinen and Guillaume Bourque},

url = {https://doi.org/10.1186/s13059-020-02038-8},

doi = {10.1186/s13059-020-02038-8},

issn = {1474-760X},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-26},

journal = {Genome Biology},

volume = {21},

number = {1},

pages = {124},

abstract = {Epigenomic studies that use next generation sequencing experiments typically rely on the alignment of reads to a reference sequence. However, because of genetic diversity and the diploid nature of the human genome, we hypothesize that using a generic reference could lead to incorrectly mapped reads and bias downstream results.},

keywords = {ChIP-seq, De novo assembly, Epigenomics, Genome graphs, Modified reference, Personalized genomes, Reference bias},

pubstate = {published},

tppubtype = {article}

}

@article{tremblay_dissection_2020,

title = {Dissection of Clinical and Gene Expression Signatures of Familial versus Multifactorial Chylomicronemia},

author = {Karine Tremblay and Daniel Gaudet and Etienne Khoury and Diane Brisson},

url = {https://doi.org/10.1210/jendso/bvaa056},

doi = {10.1210/jendso/bvaa056},

issn = {2472-1972},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-26},

journal = {Journal of the Endocrine Society},

volume = {4},

number = {bvaa056},

abstract = {Familial chylomicronemia syndrome (FCS) is a rare disorder associated with chylomicronemia (CM) and an increased risk of pancreatitis. Most individuals with CM do not have FCS but exhibit multifactorial CM (MCM), which differs from FCS in terms of risk and disease management. This study aimed to investigate clinical and gene expression profiles of FCS and MCM patients. Anthropometrics, clinical, and biochemical variables were analyzed in 57 FCS and 353 MCM patients. Gene expression analyses were performed in a subsample of 19 FCS, 28 MCM, and 15 normolipidemic controls. Receiver operating characteristic (ROC) curve analyses were performed to analyze the capacity of variables to discriminate FCS from MCM. Sustained fasting triglycerides ≥20 mmol/L (>15 mmol/L with eruptive xanthomas), history of pancreatitis, poor response to fibrates, diagnosis of CM at childhood, body mass index <22 kg/m2, and delipidated apolipoprotein B or glycerol levels <0.9 g/L and <0.05 mmol/L, respectively, had an area under the ROC curve ≥0.7. Gene expression analyses identified 142 probes differentially expressed in FCS and 32 in MCM compared with controls. Among them, 13 probes are shared between FCS and MCM; 63 are specific to FCS and 2 to MCM. Most FCS-specific or shared biomarkers are involved in inflammatory, immune, circadian, postprandial metabolism, signaling, docking systems, or receptor-mediated clearance mechanisms. This study reveals differential signatures of FCS and MCM. It opens the door to the identification of key mechanisms of CM expression and potential targets for the development of new treatments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{zhuang_sex_2020,

title = {Sex Chromosomes and Sex Phenotype Contribute to Biased DNA Methylation in Mouse Liver},

author = {Qinwei Kim-Wee Zhuang and Jose Hector Galvez and Qian Xiao and Najla AlOgayil and Jeffrey Hyacinthe and Teruko Taketo and Guillaume Bourque and Anna K Naumova},

url = {https://www.mdpi.com/2073-4409/9/6/1436},

doi = {10.3390/cells9061436},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-26},

journal = {Cells},

volume = {9},

number = {6},

pages = {1436},

abstract = {Sex biases in the genome-wide distribution of DNA methylation and gene expression levels are some of the manifestations of sexual dimorphism in mammals. To advance our understanding of the mechanisms that contribute to sex biases in DNA methylation and gene expression, we conducted whole genome bisulfite sequencing (WGBS) as well as RNA-seq on liver samples from mice with different combinations of sex phenotype and sex-chromosome complement. We compared groups of animals with different sex phenotypes, but the same genetic sexes, and vice versa, same sex phenotypes, but different sex-chromosome complements. We also compared sex-biased DNA methylation in mouse and human livers. Our data show that sex phenotype, X-chromosome dosage, and the presence of Y chromosome shape the differences in DNA methylation between males and females. We also demonstrate that sex bias in autosomal methylation is associated with sex bias in gene expression, whereas X-chromosome dosage-dependent methylation differences are not, as expected for a dosage-compensation mechanism. Furthermore, we find partial conservation between the repertoires of mouse and human genes that are associated with sex-biased methylation, an indication that gene function is likely to be an important factor in this phenomenon.},

note = {Number: 6 

Publisher: Multidisciplinary Digital Publishing Institute},

keywords = {DNA methylation, Gene expression, mouse liver, sex-chromosome complement, sexual dimorphism, whole genome bisulfite sequencing},

pubstate = {published},

tppubtype = {article}

}

@article{mohanraj_crescent_2020,

title = {CReSCENT: CanceR Single Cell ExpressioN Toolkit},

author = {Suluxan Mohanraj and Javier J Díaz-Mejía and Martin D Pham and Hillary Elrick and Mia Husić and Shaikh Rashid and Ping Luo and Prabnur Bal and Kevin Lu and Samarth Patel and Alaina Mahalanabis and Alaine Naidas and Erik Christensen and Danielle Croucher and Laura M Richards and Parisa Shooshtari and Michael Brudno and Arun K Ramani and Trevor J Pugh},

url = {https://doi.org/10.1093/nar/gkaa437},

doi = {10.1093/nar/gkaa437},

issn = {0305-1048},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-28},

journal = {Nucleic Acids Research},

volume = {48},

number = {W1},

pages = {W372--W379},

abstract = {CReSCENT: CanceR Single Cell ExpressioN Toolkit (https://crescent.cloud), is an intuitive and scalable web portal incorporating a containerized pipeline execution engine for standardized analysis of single-cell RNA sequencing (scRNA-seq) data. While scRNA-seq data for tumour specimens are readily generated, subsequent analysis requires high-performance computing infrastructure and user expertise to build analysis pipelines and tailor interpretation for cancer biology. CReSCENT uses public data sets and preconfigured pipelines that are accessible to computational biology non-experts and are user-editable to allow optimization, comparison, and reanalysis for specific experiments. Users can also upload their own scRNA-seq data for analysis and results can be kept private or shared with other users.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{couturier_single-cell_2020,

title = {Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy},

author = {Charles P Couturier and Shamini Ayyadhury and Phuong U Le and Javad Nadaf and Jean Monlong and Gabriele Riva and Redouane Allache and Salma Baig and Xiaohua Yan and Mathieu Bourgey and Changseok Lee and Yu Chang David Wang and V Wee Yong and Marie-Christine Guiot and Hamed Najafabadi and Bratislav Misic and Jack Antel and Guillaume Bourque and Jiannis Ragoussis and Kevin Petrecca},

url = {https://www.nature.com/articles/s41467-020-17186-5},

doi = {10.1038/s41467-020-17186-5},

issn = {2041-1723},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-28},

journal = {Nature Communications},

volume = {11},

number = {1},

pages = {3406},

abstract = {Cancer stem cells are critical for cancer initiation, development, and treatment resistance. Our understanding of these processes, and how they relate to glioblastoma heterogeneity, is limited. To overcome these limitations, we performed single-cell RNA sequencing on 53586 adult glioblastoma cells and 22637 normal human fetal brain cells, and compared the lineage hierarchy of the developing human brain to the transcriptome of cancer cells. We find a conserved neural tri-lineage cancer hierarchy centered around glial progenitor-like cells. We also find that this progenitor population contains the majority of the cancer’s cycling cells, and, using RNA velocity, is often the originator of the other cell types. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, suggests a possible origin for glioblastoma hierarchy, and helps to identify cancer stem cell-specific targets.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{khazaei_h33_2020,

title = {H3.3 G34W Promotes Growth and Impedes Differentiation of Osteoblast-Like Mesenchymal Progenitors in Giant Cell Tumor of Bone},

author = {Sima Khazaei and Nicolas De Jay and Shriya Deshmukh and Liam D Hendrikse and Wajih Jawhar and Carol C L Chen and Leonie G Mikael and Damien Faury and Dylan M Marchione and Joel Lanoix and Éric Bonneil and Takeaki Ishii and Siddhant U Jain and Kateryna Rossokhata and Tianna S Sihota and Robert Eveleigh and Véronique Lisi and Ashot S Harutyunyan and Sungmi Jung and Jason Karamchandani and Brendan C Dickson and Robert Turcotte and Jay S Wunder and Pierre Thibault and Peter W Lewis and Benjamin A Garcia and Stephen C Mack and Michael D Taylor and Livia Garzia and Claudia L Kleinman and Nada Jabado},

url = {https://cancerdiscovery.aacrjournals.org/content/10/12/1968},

doi = {10.1158/2159-8290.CD-20-0461},

issn = {2159-8274, 2159-8290},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-28},

journal = {Cancer Discovery},

volume = {10},

number = {12},

pages = {1968--1987},

abstract = {Glycine 34-to-tryptophan (G34W) substitutions in H3.3 arise in approximately 90% of giant cell tumor of bone (GCT). Here, we show H3.3 G34W is necessary for tumor formation. By profiling the epigenome, transcriptome, and secreted proteome of patient samples and tumor-derived cells CRISPR–Cas9-edited for H3.3 G34W, we show that H3.3K36me3 loss on mutant H3.3 alters the deposition of the repressive H3K27me3 mark from intergenic to genic regions, beyond areas of H3.3 deposition. This promotes redistribution of other chromatin marks and aberrant transcription, altering cell fate in mesenchymal progenitors and hindering differentiation. Single-cell transcriptomics reveals that H3.3 G34W stromal cells recapitulate a neoplastic trajectory from a SPP1+ osteoblast-like progenitor population toward an ACTA2+ myofibroblast-like population, which secretes extracellular matrix ligands predicted to recruit and activate osteoclasts. Our findings suggest that H3.3 G34W leads to GCT by sustaining a transformed state in osteoblast-like progenitors, which promotes neoplastic growth, pathologic recruitment of giant osteoclasts, and bone destruction. 

Significance: This study shows that H3.3 G34W drives GCT tumorigenesis through aberrant epigenetic remodeling, altering differentiation trajectories in mesenchymal progenitors. H3.3 G34W promotes in neoplastic stromal cells an osteoblast-like progenitor state that enables undue interactions with the tumor microenvironment, driving GCT pathogenesis. These epigenetic changes may be amenable to therapeutic targeting in GCT.See related commentary by Licht, p. 1794.This article is highlighted in the In This Issue feature, p. 1775},

note = {Publisher: American Association for Cancer Research 

Section: Research Articles},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{wang_preclinical_2020,

title = {A Preclinical Trial and Molecularly Annotated Patient Cohort Identify Predictive Biomarkers in Homologous Recombination–deficient Pancreatic Cancer},

author = {Yifan Wang and Jin Yong Patrick Park and Alain Pacis and Robert E Denroche and Gun Ho Jang and Amy Zhang and Adeline Cuggia and Celine Domecq and Jean Monlong and Maria Raitses-Gurevich and Robert C Grant and Ayelet Borgida and Spring Holter and Chani Stossel and Simeng Bu and Mehdi Masoomian and Ilinca M Lungu and John M S Bartlett and Julie M Wilson and Zu-Hua Gao and Yasser Riazalhosseini and Jamil Asselah and Nathaniel Bouganim and Tatiana Cabrera and Louis-Martin Boucher and David Valenti and James Biagi and Celia M T Greenwood and Paz Polak and William D Foulkes and Talia Golan and Grainne M O'Kane and Sandra E Fischer and Jennifer J Knox and Steven Gallinger and George Zogopoulos},

url = {https://clincancerres.aacrjournals.org/content/26/20/5462},

doi = {10.1158/1078-0432.CCR-20-1439},

issn = {1078-0432, 1557-3265},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-28},

journal = {Clinical Cancer Research},

volume = {26},

number = {20},

pages = {5462--5476},

abstract = {Purpose: Pancreatic ductal adenocarcinoma (PDAC) arising in patients with a germline BRCA1 or BRCA2 (gBRCA) mutation may be sensitive to platinum and PARP inhibitors (PARPi). However, treatment stratification based on gBRCA mutational status alone is associated with heterogeneous responses. 

Experimental Design: We performed a seven-arm preclinical trial consisting of 471 mice, representing 12 unique PDAC patient-derived xenografts, of which nine were gBRCA mutated. From 179 patients whose PDAC was whole-genome and transcriptome sequenced, we identified 21 cases with homologous recombination deficiency (HRD), and investigated prognostic biomarkers. 

Results: We found that biallelic inactivation of BRCA1/BRCA2 is associated with genomic hallmarks of HRD and required for cisplatin and talazoparib (PARPi) sensitivity. However, HRD genomic hallmarks persisted in xenografts despite the emergence of therapy resistance, indicating the presence of a genomic scar. We identified tumor polyploidy and a low Ki67 index as predictors of poor cisplatin and talazoparib response. In patients with HRD PDAC, tumor polyploidy and a basal-like transcriptomic subtype were independent predictors of shorter survival. To facilitate clinical assignment of transcriptomic subtype, we developed a novel pragmatic two-marker assay (GATA6:KRT17). 

Conclusions: In summary, we propose a predictive and prognostic model of gBRCA-mutated PDAC on the basis of HRD genomic hallmarks, Ki67 index, tumor ploidy, and transcriptomic subtype.},

note = {Publisher: American Association for Cancer Research 

Section: Translational Cancer Mechanisms and Therapy},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{moreau_mutations_2020,

title = {Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia},

author = {Clara A Moreau and Sebastian G W Urchs and Kumar Kuldeep and Pierre Orban and Catherine Schramm and Guillaume Dumas and Aurélie Labbe and Guillaume Huguet and Elise Douard and Pierre-Olivier Quirion and Amy Lin and Leila Kushan and Stephanie Grot and David Luck and Adrianna Mendrek and Stephane Potvin and Emmanuel Stip and Thomas Bourgeron and Alan C Evans and Carrie E Bearden and Pierre Bellec and Sebastien Jacquemont},

url = {https://www.nature.com/articles/s41467-020-18997-2},

doi = {10.1038/s41467-020-18997-2},

issn = {2041-1723},

year  = {2020},

date = {2020-01-01},

urldate = {2021-05-28},

journal = {Nature Communications},

volume = {11},

number = {1},

pages = {5272},

abstract = {16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Eveleigh2019,

title = {A point mutation in the linker domain of mouse STAT5A is associated with impaired NK-cell regulation},

author = {Robert Eveleigh, Guillaume Bourque},

url = {https://www.nature.com/articles/s41435-019-0088-6#author-information},

doi = {https://doi.org/10.1038/s41435-019-0088-6},

year  = {2019},

date = {2019-10-08},

abstract = {The transcription factor STAT5 is critical for peripheral NK-cell survival, proliferation, and cytotoxic function. STAT5 refers to two highly related proteins, STAT5A and STAT5B. In this study, we verified the importance of STAT5A isoform for NK cells. We characterized an incidental chemically induced W484G mutation in the Stat5a gene and found that this mutation was associated with a reduction of STAT5A protein expression. Closer examination of NK-cell subsets from Stat5a mutant mice showed marked reductions in NK-cell number and maturation. IL-15 treatment of Stat5a mutant NK cells exhibited defective induction of both STAT5 and mTOR signaling pathways and reduced expression of granzyme B and IFN-γ. Finally, we observed that Stat5a mutant mice revealed more tumor growth upon injection of RMA-S tumor cell line. Overall, our results demonstrate that the W484G mutation in the linker domain of STAT5A is sufficient to compromise STAT5A function in NK-cell homeostasis, responsiveness, and tumoricidal function.},

keywords = {Immunogenetics, Innate immune cells},

pubstate = {published},

tppubtype = {article}

}

@article{Stucklin2019,

title = {Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas},

author = {Ana S. Guerreiro Stucklin, Scott Ryall},

url = {https://www.nature.com/articles/s41467-019-12187-5#citeas},

doi = {https://doi.org/10.1038/s41467-019-12187-5},

year  = {2019},

date = {2019-09-25},

abstract = {Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.},

keywords = {Cancer genomics, Molecular medicine},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1080/15592294.2019.1581592,

title = {Don’t brush off buccal data heterogeneity},

author = {Andrei L Turinsky and Darci T Butcher and Sanaa Choufani and Rosanna Weksberg and Michael Brudno},

url = {https://doi.org/10.1080/15592294.2019.1581592},

doi = {10.1080/15592294.2019.1581592},

year  = {2019},

date = {2019-01-01},

journal = {Epigenetics},

volume = {14},

number = {2},

pages = {109-117},

publisher = {Taylor & Francis},

note = {PMID: 30821575},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1161/CIRCRESAHA.118.313250,

title = {Whole Exome Sequencing Reveals the Major Genetic Contributors to Nonsyndromic Tetralogy of Fallot},

author = {Donna J Page and Matthieu J Miossec and Simon G Williams and Richard M Monaghan and Elisavet Fotiou and Heather J Cordell and Louise Sutcliffe and Ana Topf and Mathieu Bourgey and Guillaume Bourque and Robert Eveleigh and Sally L Dunwoodie and David S Winlaw and Shoumo Bhattacharya and Jeroen Breckpot and Koenraad Devriendt and Marc Gewillig and David J Brook and Kerry J Setchfield and Frances A Bu’Lock and John O’Sullivan and Graham Stuart and Connie R Bezzina and Barbara J M Mulder and Alex V Postma and James R Bentham and Martin Baron and Sanjeev S Bhaskar and Graeme C Black and William G Newman and Kathryn E Hentges and Mark G Lathrop and Mauro Santibanez-Koref and Bernard D Keavney},

url = {https://www.ahajournals.org/doi/abs/10.1161/CIRCRESAHA.118.313250},

doi = {10.1161/CIRCRESAHA.118.313250},

year  = {2019},

date = {2019-01-01},

journal = {Circulation Research},

volume = {124},

number = {4},

pages = {553-563},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{laperle_epigenomic_2019,

title = {The epiGenomic Efficient Correlator (epiGeEC) tool allows fast comparison of user datasets with thousands of public epigenomic datasets},

author = {Jonathan Laperle and Simon Hébert-Deschamps and Joanny Raby and David A de Lima Morais and Michel Barrette and David Bujold and Charlotte Bastin and Marc-Antoine Robert and Jean-François Nadeau and Marie Harel and Alexei Nordell-Markovits and Alain Veilleux and Guillaume Bourque and Pierre-Étienne Jacques},

url = {https://doi.org/10.1093/bioinformatics/bty655},

doi = {10.1093/bioinformatics/bty655},

issn = {1367-4803},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {Bioinformatics},

volume = {35},

number = {4},

pages = {674--676},

abstract = {In recent years, major initiatives such as the International Human Epigenome Consortium have generated thousands of high-quality genome-wide datasets for a large variety of assays and cell types. This data can be used as a reference to assess whether the signal from a user-provided dataset corresponds to its expected experiment, as well as to help reveal unexpected biological associations. We have developed the epiGenomic Efficient Correlator (epiGeEC) tool to enable genome-wide comparisons of very large numbers of datasets. A public Galaxy implementation of epiGeEC allows comparison of user datasets with thousands of public datasets in a few minutes.The source code is available at https://bitbucket.org/labjacquespe/epigeec and the Galaxy implementation at http://epigeec.genap.ca.Supplementary data are available at Bioinformatics online.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{shokoohi_hidden_2019,

title = {A hidden markov model for identifying differentially methylated sites in bisulfite sequencing data},

author = {Farhad Shokoohi and David A Stephens and Guillaume Bourque and Tomi Pastinen and Celia M T Greenwood and Aurélie Labbe},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/biom.12965},

doi = {https://doi.org/10.1111/biom.12965},

issn = {1541-0420},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {Biometrics},

volume = {75},

number = {1},

pages = {210--221},

abstract = {DNA methylation studies have enabled researchers to understand methylation patterns and their regulatory roles in biological processes and disease. However, only a limited number of statistical approaches have been developed to provide formal quantitative analysis. Specifically, a few available methods do identify differentially methylated CpG (DMC) sites or regions (DMR), but they suffer from limitations that arise mostly due to challenges inherent in bisulfite sequencing data. These challenges include: (1) that read-depths vary considerably among genomic positions and are often low; (2) both methylation and autocorrelation patterns change as regions change; and (3) CpG sites are distributed unevenly. Furthermore, there are several methodological limitations: almost none of these tools is capable of comparing multiple groups and/or working with missing values, and only a few allow continuous or multiple covariates. The last of these is of great interest among researchers, as the goal is often to find which regions of the genome are associated with several exposures and traits. To tackle these issues, we have developed an efficient DMC identification method based on Hidden Markov Models (HMMs) called “DMCHMM” which is a three-step approach (model selection, prediction, testing) aiming to address the aforementioned drawbacks. Our proposed method is different from other HMM methods since it profiles methylation of each sample separately, hence exploiting inter-CpG autocorrelation within samples, and it is more flexible than previous approaches by allowing multiple hidden states. Using simulations, we show that DMCHMM has the best performance among several competing methods. An analysis of cell-separated blood methylation profiles is also provided.},

note = {_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/biom.12965},

keywords = {Blood cell-separated data, Differentially methylated region, Next-generation sequencing, Read-depth},

pubstate = {published},

tppubtype = {article}

}

@article{choufani_impact_2019,

title = {Impact of assisted reproduction, infertility, sex and paternal factors on the placental DNA methylome},

author = {Sanaa Choufani and Andrei L Turinsky and Nir Melamed and Ellen Greenblatt and Michael Brudno and Anick Bérard and William D Fraser and Rosanna Weksberg and Jacquetta Trasler and Patricia Monnier and 3D cohort study group},

url = {https://doi.org/10.1093/hmg/ddy321},

doi = {10.1093/hmg/ddy321},

issn = {0964-6906},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {Human Molecular Genetics},

volume = {28},

number = {3},

pages = {372--385},

abstract = {Children conceived using Assisted Reproductive Technologies (ART) have a higher incidence of growth and birth defects, attributable in part to epigenetic perturbations. Both ART and germline defects associated with parental infertility could interfere with epigenetic reprogramming events in germ cells or early embryos. Mouse models indicate that the placenta is more susceptible to the induction of epigenetic abnormalities than the embryo, and thus the placental methylome may provide a sensitive indicator of ‘at risk’ conceptuses. Our goal was to use genome-wide profiling to examine the extent of epigenetic abnormalities in matched placentas from an ART/infertility group and control singleton pregnancies (n = 44/group) from a human prospective longitudinal birth cohort, the Design, Develop, Discover (3D) Study. Principal component analysis revealed a group of ART outliers. The ART outlier group was enriched for females and a subset of placentas showing loss of methylation of several imprinted genes including GNAS, SGCE, KCNQT1OT1 and BLCAP/NNAT. Within the ART group, placentas from pregnancies conceived with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) showed distinct epigenetic profiles as compared to those conceived with less invasive procedures (ovulation induction, intrauterine insemination). Male factor infertility and paternal age further differentiated the IVF/ICSI group, suggesting an interaction of infertility and techniques in perturbing the placental epigenome. Together, the results suggest that the human placenta is sensitive to the induction of epigenetic defects by ART and/or infertility, and we stress the importance of considering both sex and paternal factors and that some but not all ART conceptuses will be susceptible.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cvetkovska_enigmatic_2019,

title = {The enigmatic loss of light-independent chlorophyll biosynthesis from an Antarctic green alga in a light-limited environment},

author = {Marina Cvetkovska and Shane Orgnero and Norman P A Hüner and David Roy Smith},

url = {https://nph.onlinelibrary.wiley.com/doi/abs/10.1111/nph.15623},

doi = {https://doi.org/10.1111/nph.15623},

issn = {1469-8137},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {New Phytologist},

volume = {222},

number = {2},

pages = {651--656},

note = {_eprint: https://nph.onlinelibrary.wiley.com/doi/pdf/10.1111/nph.15623},

keywords = {Chlamydomonas sp. UWO241, chlorophyll, DPOR, photosynthesis, psychrophile},

pubstate = {published},

tppubtype = {article}

}

@article{,

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {Epigenetics},

volume = {14},

number = {2},

pages = {109--117},

keywords = {buccal epithelial cells, DNA methylation, epigenetics, tissue heterogeneity},

pubstate = {published},

tppubtype = {article}

}

@article{untereiner_gaba_2019,

title = {GABA promotes β-cell proliferation, but does not overcome impaired glucose homeostasis associated with diet-induced obesity},

author = {Ashley Untereiner and Shaaban Abdo and Alpana Bhattacharjee and Himaben Gohil and Farzaneh Pourasgari and Neke Ibeh and Mi Lai and Battsetseg Batchuluun and Anthony Wong and Nicholas Khuu and Ying Liu and Dana Al Rijjal and Neil Winegarden and Carl Virtanen and Beverley A Orser and Over Cabrera and Gabor Varga and Jonathan Rocheleau and Feihan F Dai and Michael B Wheeler},

url = {https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.201801397R},

doi = {https://doi.org/10.1096/fj.201801397R},

issn = {1530-6860},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {The FASEB Journal},

volume = {33},

number = {3},

pages = {3968--3984},

abstract = {γ-Aminobutyric acid (GABA) administration has been shown to increase β-cell mass, leading to a reversal of type 1 diabetes in mice. Whether GABA has any effect on β cells of healthy and prediabetic/glucose-intolerant obese mice remains unknown. In the present study, we show that oral GABA administration (ad libitum) to mice indeed increased pancreatic β-cell mass, which led to a modest enhancement in insulin secretion and glucose tolerance. However, GABA treatment did not further increase insulin-positive islet area in high fat diet-fed mice and was unable to prevent or reverse glucose intolerance and insulin resistance. Mechanistically, whether in vivo or in vitro, GABA treatment increased β-cell proliferation. In vitro, the effect was shown to be mediated via the GABAA receptor. Single-cell RNA sequencing analysis revealed that GABA preferentially up-regulated pathways linked to β-cell proliferation and simultaneously down-regulated those networks required for other processes, including insulin biosynthesis and metabolism. Interestingly, single-cell differential expression analysis revealed GABA treatment gave rise to a distinct subpopulation of β cells with a unique transcriptional signature, including urocortin 3 (ucn3), wnt4, and hepacam2. Taken together, this study provides new mechanistic insight into the proliferative nature of GABA but suggests that β-cell compensation associated with prediabetes overlaps with, and negates, its proliferative effects.—Untereiner, A., Abdo, S., Bhattacharjee, A., Gohil, H., Pourasgari, F., Ibeh, N., Lai, M., Batchuluun, B., Wong, A., Khuu, N., Liu, Y., Al Rijjal, D., Winegarden, N., Virtanen, C., Orser, B. A., Cabrera, O., Varga, G., Rocheleau, J., Dai, F. F., Wheeler, M. B. GABA promotes β-cell proliferation, but does not overcome impaired glucose homeostasis associated with diet-induced obesity. FASEB J. 33, 3968–3984 (2019). www.fasebj.org},

note = {_eprint: https://faseb.onlinelibrary.wiley.com/doi/pdf/10.1096/fj.201801397R},

keywords = {diet-induced obesity, GABAA receptor, glucose tolerance, insulin secretion, single cell RNA-seq},

pubstate = {published},

tppubtype = {article}

}

@article{sukhai_somatic_2019,

title = {Somatic Tumor Variant Filtration Strategies to Optimize Tumor-Only Molecular Profiling Using Targeted Next-Generation Sequencing Panels},

author = {Mahadeo A Sukhai and Maksym Misyura and Mariam Thomas and Swati Garg and Tong Zhang and Natalie Stickle and Carl Virtanen and Philippe L Bedard and Lillian L Siu and Tina Smets and Gert Thijs and Steven Van Vooren and Suzanne Kamel-Reid and Tracy L Stockley},

url = {https://www.jmdjournal.org/article/S1525-1578(17)30598-6/abstract},

doi = {10.1016/j.jmoldx.2018.09.008},

issn = {1525-1578},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {The Journal of Molecular Diagnostics},

volume = {21},

number = {2},

pages = {261--273},

abstract = {textlessptextgreaterA common approach in clinical diagnostic laboratories to variant assessment from tumor molecular profiling is sequencing of genomic DNA extracted from both tumor (somatic) and normal (germline) tissue, with subsequent variant comparison to identify true somatic variants with potential impact on patient treatment or prognosis. However, challenges exist in paired tumor-normal testing, including increased cost of dual sample testing and identification of germline cancer predisposing variants. Alternatively, somatic variants can be identified by textitin silico tumor-only variant filtration precluding the need for matched normal testing. The barrier to tumor-only variant filtration is defining a reliable approach, with high sensitivity and specificity to identify somatic variants. In this study, we used retrospective data sets from paired tumor-normal samples tested on small (48 gene) and large (555 gene) targeted next-generation sequencing panels, to model algorithms for tumor-only variants classification. The optimal algorithm required an ordinal filtering approach using information from variant population databases (1000 Genomes Phase 3, ESP6500, ExAC), clinical mutation databases (ClinVar), and information on recurring clinically relevant somatic variants. Overall the tumor-only variant filtration strategy described in this study can define clinically relevant somatic variants from tumor-only analysis with sensitivity of 97% to 99% and specificity of 87% to 94%, and with significant potential utility for clinical laboratories implementing tumor-only molecular profiling.textless/ptextgreater},

note = {Publisher: Elsevier},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{gonorazky_expanding_2019,

title = {Expanding the Boundaries of RNA Sequencing as a Diagnostic Tool for Rare Mendelian Disease},

author = {Hernan D Gonorazky and Sergey Naumenko and Arun K Ramani and Viswateja Nelakuditi and Pouria Mashouri and Peiqui Wang and Dennis Kao and Krish Ohri and Senthuri Viththiyapaskaran and Mark A Tarnopolsky and Katherine D Mathews and Steven A Moore and Andres N Osorio and David Villanova and Dwi U Kemaladewi and Ronald D Cohn and Michael Brudno and James J Dowling},

url = {https://www.cell.com/ajhg/abstract/S0002-9297(19)30012-6},

doi = {10.1016/j.ajhg.2019.01.012},

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

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {The American Journal of Human Genetics},

volume = {104},

number = {3},

pages = {466--483},

note = {Publisher: Elsevier},

keywords = {diagnostics, Mendelian disease, muscular dystrophy, myotubes, RNA-seq, Transcriptomics, transdifferentiation},

pubstate = {published},

tppubtype = {article}

}

@article{chong_metaboanalystr_2019,

title = {MetaboAnalystR 2.0: From Raw Spectra to Biological Insights},

author = {Jasmine Chong and Mai Yamamoto and Jianguo Xia},

url = {https://www.mdpi.com/2218-1989/9/3/57},

doi = {10.3390/metabo9030057},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {Metabolites},

volume = {9},

number = {3},

pages = {57},

abstract = {Global metabolomics based on high-resolution liquid chromatography mass spectrometry (LC-MS) has been increasingly employed in recent large-scale multi-omics studies. Processing and interpretation of these complex metabolomics datasets have become a key challenge in current computational metabolomics. Here, we introduce MetaboAnalystR 2.0 for comprehensive LC-MS data processing, statistical analysis, and functional interpretation. Compared to the previous version, this new release seamlessly integrates XCMS and CAMERA to support raw spectral processing and peak annotation, and also features high-performance implementations of mummichog and GSEA approaches for predictions of pathway activities. The application and utility of the MetaboAnalystR 2.0 workflow were demonstrated using a synthetic benchmark dataset and a clinical dataset. In summary, MetaboAnalystR 2.0 offers a unified and flexible workflow that enables end-to-end analysis of LC-MS metabolomics data within the open-source R environment.},

note = {Number: 3 

Publisher: Multidisciplinary Digital Publishing Institute},

keywords = {enrichment analysis, global metabolomics, LC-MS, pathway analysis, spectra processing},

pubstate = {published},

tppubtype = {article}

}

@article{zhou_networkanalyst_2019,

title = {NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis},

author = {Guangyan Zhou and Othman Soufan and Jessica Ewald and Robert E W Hancock and Niladri Basu and Jianguo Xia},

url = {https://doi.org/10.1093/nar/gkz240},

doi = {10.1093/nar/gkz240},

issn = {0305-1048},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {Nucleic Acids Research},

volume = {47},

number = {W1},

pages = {W234--W241},

abstract = {The growing application of gene expression profiling demands powerful yet user-friendly bioinformatics tools to support systems-level data understanding. NetworkAnalyst was first released in 2014 to address the key need for interpreting gene expression data within the context of protein-protein interaction (PPI) networks. It was soon updated for gene expression meta-analysis with improved workflow and performance. Over the years, NetworkAnalyst has been continuously updated based on community feedback and technology progresses. Users can now perform gene expression profiling for 17 different species. In addition to generic PPI networks, users can now create cell-type or tissue specific PPI networks, gene regulatory networks, gene co-expression networks as well as networks for toxicogenomics and pharmacogenomics studies. The resulting networks can be customized and explored in 2D, 3D as well as Virtual Reality (VR) space. For meta-analysis, users can now visually compare multiple gene lists through interactive heatmaps, enrichment networks, Venn diagrams or chord diagrams. In addition, users have the option to create their own data analysis projects, which can be saved and resumed at a later time. These new features are released together as NetworkAnalyst 3.0, freely available at https://www.networkanalyst.ca.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{gonzalez_anchor_2019,

title = {ANCHOR: a 16S rRNA gene amplicon pipeline for microbial analysis of multiple environmental samples},

author = {Emmanuel Gonzalez and Frederic E Pitre and Nicholas J B Brereton},

url = {https://sfamjournals.onlinelibrary.wiley.com/doi/abs/10.1111/1462-2920.14632},

doi = {https://doi.org/10.1111/1462-2920.14632},

issn = {1462-2920},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {Environmental Microbiology},

volume = {21},

number = {7},

pages = {2440--2468},

abstract = {Analysis of 16S ribosomal RNA (rRNA) gene amplification data for microbial barcoding can be inaccurate across complex environmental samples. A method, ANCHOR, is presented and designed for improved species-level microbial identification using paired-end sequences directly, multiple high-complexity samples and multiple reference databases. A standard operating procedure (SOP) is reported alongside benchmarking against artificial, single sample and replicated mock data sets. The method is then directly tested using a real-world data set from surface swabs of the International Space Station (ISS). Simple mock community analysis identified 100% of the expected species and 99% of expected gene copy variants (100% identical). A replicated mock community revealed similar or better numbers of expected species than MetaAmp, DADA2, Mothur and QIIME1. Analysis of the ISS microbiome identified 714 putative unique species/strains and differential abundance analysis distinguished significant differences between the Destiny module (U.S. laboratory) and Harmony module (sleeping quarters). Harmony was remarkably dominated by human gastrointestinal tract bacteria, similar to enclosed environments on earth; however, Destiny module bacteria also derived from nonhuman microbiome carriers present on the ISS, the laboratory's research animals. ANCHOR can help substantially improve sequence resolution of 16S rRNA gene amplification data within biologically replicated environmental experiments and integrated multidatabase annotation enhances interpretation of complex, nonreference microbiomes.},

note = {_eprint: https://sfamjournals.onlinelibrary.wiley.com/doi/pdf/10.1111/1462-2920.14632},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{breeze_eforge_2019,

title = {eFORGE v2.0: updated analysis of cell type-specific signal in epigenomic data},

author = {Charles E Breeze and Alex P Reynolds and Jenny van Dongen and Ian Dunham and John Lazar and Shane Neph and Jeff Vierstra and Guillaume Bourque and Andrew E Teschendorff and John A Stamatoyannopoulos and Stephan Beck},

url = {https://doi.org/10.1093/bioinformatics/btz456},

doi = {10.1093/bioinformatics/btz456},

issn = {1367-4803},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {Bioinformatics},

volume = {35},

number = {22},

pages = {4767--4769},

abstract = {The Illumina Infinium EPIC BeadChip is a new high-throughput array for DNA methylation analysis, extending the earlier 450k array by over 400 000 new sites. Previously, a method named eFORGE was developed to provide insights into cell type-specific and cell-composition effects for 450k data. Here, we present a significantly updated and improved version of eFORGE that can analyze both EPIC and 450k array data. New features include analysis of chromatin states, transcription factor motifs and DNase I footprints, providing tools for epigenome-wide association study interpretation and epigenome editing.eFORGE v2.0 is implemented as a web tool available from https://eforge.altiusinstitute.org and https://eforge-tf.altiusinstitute.org/.Supplementary data are available at Bioinformatics online.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{bourgey_genpipes_2019,

title = {GenPipes: an open-source framework for distributed and scalable genomic analyses},

author = {Mathieu Bourgey and Rola Dali and Robert Eveleigh and Kuang Chung Chen and Louis Letourneau and Joel Fillon and Marc Michaud and Maxime Caron and Johanna Sandoval and Francois Lefebvre and Gary Leveque and Eloi Mercier and David Bujold and Pascale Marquis and Patrick Tran Van and David Anderson de Lima Morais and Julien Tremblay and Xiaojian Shao and Edouard Henrion and Emmanuel Gonzalez and Pierre-Olivier Quirion and Bryan Caron and Guillaume Bourque},

url = {https://doi.org/10.1093/gigascience/giz037},

doi = {10.1093/gigascience/giz037},

issn = {2047-217X},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {GigaScience},

volume = {8},

number = {giz037},

abstract = {With the decreasing cost of sequencing and the rapid developments in genomics technologies and protocols, the need for validated bioinformatics software that enables efficient large-scale data processing is growing.Here we present GenPipes, a flexible Python-based framework that facilitates the development and deployment of multi-step workflows optimized for high-performance computing clusters and the cloud. GenPipes already implements 12 validated and scalable pipelines for various genomics applications, including RNA sequencing, chromatin immunoprecipitation sequencing, DNA sequencing, methylation sequencing, Hi-C, capture Hi-C, metagenomics, and Pacific Biosciences long-read assembly. The software is available under a GPLv3 open source license and is continuously updated to follow recent advances in genomics and bioinformatics. The framework has already been configured on several servers, and a Docker image is also available to facilitate additional installations.GenPipes offers genomics researchers a simple method to analyze different types of data, customizable to their needs and resources, as well as the flexibility to create their own workflows.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{morou_altered_2019,

title = {Altered differentiation is central to HIV-specific CD4 + Ŧ cell dysfunction in progressive disease},

author = {Antigoni Morou and Elsa Brunet-Ratnasingham and Mathieu Dubé and Roxanne Charlebois and Eloi Mercier and Sam Darko and Nathalie Brassard and Krystelle Nganou-Makamdop and Sahaana Arumugam and Gabrielle Gendron-Lepage and Lifei Yang and Julia Niessl and Amy E Baxter and James M Billingsley and Premeela A Rajakumar and François Lefebvre and Paul R Johnson and Cécile Tremblay and Jean-Pierre Routy and Richard T Wyatt and Andrés Finzi and Daniel C Douek and Daniel E Kaufmann},

url = {https://www.nature.com/articles/s41590-019-0418-x},

doi = {10.1038/s41590-019-0418-x},

issn = {1529-2916},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-19},

journal = {Nature Immunology},

volume = {20},

number = {8},

pages = {1059--1070},

abstract = {Dysfunction of virus-specific CD4+ T cells in chronic human infections is poorly understood. We performed genome-wide transcriptional analyses and functional assays of CD4+ T cells specific for human immunodeficiency virus (HIV) from HIV-infected people before and after initiation of antiretroviral therapy (ART). A follicular helper T cell (TFH cell)-like profile characterized HIV-specific CD4+ T cells in viremic infection. HIV-specific CD4+ T cells from people spontaneously controlling the virus (elite controllers) robustly expressed genes associated with the TH1, TH17 and TH22 subsets of helper T cells. Viral suppression by ART resulted in a distinct transcriptional landscape, with a reduction in the expression of genes associated with TFH cells, but persistently low expression of genes associated with TH1, TH17 and TH22 cells compared to the elite controller profile. Thus, altered differentiation is central to the impairment of HIV-specific CD4+ T cells and involves both gain of function and loss of function.},

note = {Number: 8 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{siu_functional_2019,

title = {Functional DNA methylation signatures for autism spectrum disorder genomic risk loci: 16p11.2 deletions and CHD8 variants},

author = {M T Siu and D T Butcher and A L Turinsky and C Cytrynbaum and D J Stavropoulos and S Walker and O Caluseriu and M Carter and Y Lou and R Nicolson and S Georgiades and P Szatmari and E Anagnostou and S W Scherer and S Choufani and M Brudno and R Weksberg},

url = {https://doi.org/10.1186/s13148-019-0684-3},

doi = {10.1186/s13148-019-0684-3},

issn = {1868-7083},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-26},

journal = {Clinical Epigenetics},

volume = {11},

number = {1},

pages = {103},

abstract = {Autism spectrum disorder (ASD) is a common and etiologically heterogeneous neurodevelopmental disorder. Although many genetic causes have been identified (textgreater 200 ASD-risk genes), no single gene variant accounts for textgreater 1% of all ASD cases. A role for epigenetic mechanisms in ASD etiology is supported by the fact that many ASD-risk genes function as epigenetic regulators and evidence that epigenetic dysregulation can interrupt normal brain development. Gene-specific DNAm profiles have been shown to assist in the interpretation of variants of unknown significance. Therefore, we investigated the epigenome in patients with ASD or two of the most common genomic variants conferring increased risk for ASD. Genome-wide DNA methylation (DNAm) was assessed using the Illumina Infinium HumanMethylation450 and MethylationEPIC arrays in blood from individuals with ASD of heterogeneous, undefined etiology (n = 52), and individuals with 16p11.2 deletions (16p11.2del},

keywords = {Autism spectrum disorder, DNA methylation, epigenetics, Genetic stratification, Genomic variants, Heterogeneity},

pubstate = {published},

tppubtype = {article}

}

@article{chang_regulatory_2019,

title = {Regulatory interaction between the ZPBP2-ORMDL3/Zpbp2-Ormdl3 region and the circadian clock},

author = {Matthew L Chang and Sanny Moussette and Enrique Gamero-Estevez and José Héctor Gálvez and Victoria Chiwara and Indra R Gupta and Aimee K Ryan and Anna K Naumova},

url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223212},

doi = {10.1371/journal.pone.0223212},

issn = {1932-6203},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-26},

journal = {PLOS ONE},

volume = {14},

number = {9},

pages = {e0223212},

abstract = {Genome-wide association study (GWAS) loci for several immunity-mediated diseases (early onset asthma, inflammatory bowel disease (IBD), primary biliary cholangitis, and rheumatoid arthritis) map to chromosomal region 17q12-q21. The predominant view is that association between 17q12-q21 alleles and increased risk of developing asthma or IBD is due to regulatory variants. ORM sphingolipid biosynthesis regulator (ORMDL3) residing in this region is the most promising gene candidate for explaining association with disease. However, the relationship between 17q12-q21 alleles and disease is complex suggesting contributions from other factors, such as trans-acting genetic and environmental modifiers or circadian rhythms. Circadian rhythms regulate expression levels of thousands of genes and their dysregulation is implicated in the etiology of several common chronic inflammatory diseases. However, their role in the regulation of the 17q12-q21 genes has not been investigated. Moreover, the core clock gene nuclear receptor subfamily 1, group D, member 1 (NR1D1) resides about 200 kb distal to the GWAS region. We hypothesized that circadian rhythms influenced gene expression levels in 17q12-q21 region and conversely, regulatory elements in this region influenced transcription of the core clock gene NR1D1 in cis. To test these hypotheses, we examined the diurnal expression profiles of zona pellucida binding protein 2 (ZPBP2/Zpbp2), gasdermin B (GSDMB), and ORMDL3/Ormdl3 in human and mouse tissues and analyzed the impact of genetic variation in the ZPBP2/Zpbp2 region on NR1D1/Nr1d1 expression. We found that Ormdl3 and Zpbp2 were controlled by the circadian clock in a tissue-specific fashion. We also report that deletion of the Zpbp2 region altered the expression profile of Nr1d1 in lungs and ileum in a time-dependent manner. In liver, the deletion was associated with enhanced expression of Ormdl3. We provide the first evidence that disease-associated genes Zpbp2 and Ormdl3 are regulated by circadian rhythms and the Zpbp2 region influences expression of the core clock gene Nr1d1.},

note = {Publisher: Public Library of Science},

keywords = {Asthma, Circadian oscillators, Circadian rhythms, Gene expression, Gene regulation, Genetic oscillators, Ileum, Transcriptional control},

pubstate = {published},

tppubtype = {article}

}

@article{grajcarek_genome-wide_2019,

title = {Genome-wide microhomologies enable precise template-free editing of biologically relevant deletion mutations},

author = {Janin Grajcarek and Jean Monlong and Yoko Nishinaka-Arai and Michiko Nakamura and Miki Nagai and Shiori Matsuo and David Lougheed and Hidetoshi Sakurai and Megumu K Saito and Guillaume Bourque and Knut Woltjen},

url = {https://www.nature.com/articles/s41467-019-12829-8},

doi = {10.1038/s41467-019-12829-8},

issn = {2041-1723},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-26},

journal = {Nature Communications},

volume = {10},

number = {1},

pages = {4856},

abstract = {The functional effect of a gene edit by designer nucleases depends on the DNA repair outcome at the targeted locus. While non-homologous end joining (NHEJ) repair results in various mutations, microhomology-mediated end joining (MMEJ) creates precise deletions based on the alignment of flanking microhomologies (µHs). Recently, the sequence context surrounding nuclease-induced double strand breaks (DSBs) has been shown to predict repair outcomes, for which µH plays an important role. Here, we survey naturally occurring human deletion variants and identify that 11 million or 57% are flanked by µHs, covering 88% of protein-coding genes. These biologically relevant mutations are candidates for precise creation in a template-free manner by MMEJ repair. Using CRISPR-Cas9 in human induced pluripotent stem cells (hiPSCs), we efficiently create pathogenic deletion mutations for demonstrable disease models with both gain- and loss-of-function phenotypes. We anticipate this dataset and gene editing strategy to enable functional genetic studies and drug screening.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{minerbi_altered_2019,

title = {Altered microbiome composition in individuals with fibromyalgia},

author = {Amir Minerbi and Emmanuel Gonzalez and Nicholas J B Brereton and Abraham Anjarkouchian and Ken Dewar and Mary-Ann Fitzcharles and Stéphanie Chevalier and Yoram Shir},

url = {https://journals.lww.com/pain/Fulltext/2019/11000/Altered_microbiome_composition_in_individuals_with.18.aspx},

doi = {10.1097/j.pain.0000000000001640},

issn = {0304-3959},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-26},

journal = {PAIN},

volume = {160},

number = {11},

pages = {2589--2602},

abstract = {Fibromyalgia (FM) is a prevalent syndrome, characterised by chronic widespread pain, fatigue, and impaired sleep, that is challenging to diagnose and difficult to treat. The microbiomes of 77 women with FM and that of 79 control participants were compared using 16S rRNA gene amplification and whole-genome sequencing. When comparing FM patients with unrelated controls using differential abundance analysis, significant differences were revealed in several bacterial taxa. Variance in the composition of the microbiomes was explained by FM-related variables more than by any other innate or environmental variable and correlated with clinical indices of FM. In line with observed alteration in butyrate-metabolising species, targeted serum metabolite analysis verified differences in the serum levels of butyrate and propionate in FM patients. Using machine-learning algorithms, the microbiome composition alone allowed for the classification of patients and controls (receiver operating characteristic area under the curve 87.8%). To the best of our knowledge, this is the first demonstration of gut microbiome alteration in nonvisceral pain. This observation paves the way for further studies, elucidating the pathophysiology of FM, developing diagnostic aids and possibly allowing for new treatment modalities to be explored.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{jessa_stalled_2019,

title = {Stalled developmental programs at the root of pediatric brain tumors},

author = {Selin Jessa and Alexis Blanchet-Cohen and Brian Krug and Maria Vladoiu and Marie Coutelier and Damien Faury and Brice Poreau and Nicolas De Jay and Steven Hébert and Jean Monlong and Todd W Farmer and Laura K Donovan and Yixing Hu and Melissa K McConechy and Florence M G Cavalli and Leonie G Mikael and Benjamin Ellezam and Maxime Richer and Andréa Allaire and Alexander G Weil and Jeffrey Atkinson and Jean-Pierre Farmer and Roy W R Dudley and Valerie Larouche and Louis Crevier and Steffen Albrecht and Mariella G Filbin and Hervé Sartelet and Pierre-Eric Lutz and Corina Nagy and Gustavo Turecki and Santiago Costantino and Peter B Dirks and Keith K Murai and Guillaume Bourque and Jiannis Ragoussis and Livia Garzia and Michael D Taylor and Nada Jabado and Claudia L Kleinman},

url = {https://www.nature.com/articles/s41588-019-0531-7},

doi = {10.1038/s41588-019-0531-7},

issn = {1546-1718},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-26},

journal = {Nature Genetics},

volume = {51},

number = {12},

pages = {1702--1713},

abstract = {Childhood brain tumors have suspected prenatal origins. To identify vulnerable developmental states, we generated a single-cell transcriptome atlas of textgreater65,000 cells from embryonal pons and forebrain, two major tumor locations. We derived signatures for 191 distinct cell populations and defined the regional cellular diversity and differentiation dynamics. Projection of bulk tumor transcriptomes onto this dataset shows that WNT medulloblastomas match the rhombic lip-derived mossy fiber neuronal lineage and embryonal tumors with multilayered rosettes fully recapitulate a neuronal lineage, while group 2a/b atypical teratoid/rhabdoid tumors may originate outside the neuroectoderm. Importantly, single-cell tumor profiles reveal highly defined cell hierarchies that mirror transcriptional programs of the corresponding normal lineages. Our findings identify impaired differentiation of specific neural progenitors as a common mechanism underlying these pediatric cancers and provide a rational framework for future modeling and therapeutic interventions.},

note = {Number: 12 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{saulnier_benefits_2019,

title = {Benefits and barriers in the design of harmonized access agreements for international data sharing},

author = {Katie M Saulnier and David Bujold and Stephanie O M Dyke and Charles Dupras and Stephan Beck and Guillaume Bourque and Yann Joly},

url = {https://www.nature.com/articles/s41597-019-0310-4},

doi = {10.1038/s41597-019-0310-4},

issn = {2052-4463},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-26},

journal = {Scientific Data},

volume = {6},

number = {1},

pages = {297},

abstract = {In the past decade, there has been a surge in the number of sensitive human genomic and health datasets available to researchers via Data Access Agreements (DAAs) and managed by Data Access Committees (DACs). As this form of sharing increases, so do the challenges of achieving a reasonable level of data protection, particularly in the context of international data sharing. Here, we consider how excessive variation across DAAs can hinder these goals, and suggest a core set of clauses that could prove useful in future attempts to harmonize data governance.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sengar_control_2019,

title = {Control of Long-Term Synaptic Potentiation and Learning by Alternative Splicing of the NMDA Receptor Subunit GluN1},

author = {Ameet S Sengar and Hongbin Li and Wenbo Zhang and Celeste Leung and Arun K Ramani and Ner Mu Saw and Yongqian Wang and YuShan Tu and Joel P Ross and Stephen W Scherer and James Ellis and Michael Brudno and Zhengping Jia and Michael W Salter},

url = {https://www.cell.com/cell-reports/abstract/S2211-1247(19)31585-2},

doi = {10.1016/j.celrep.2019.11.087},

issn = {2211-1247},

year  = {2019},

date = {2019-01-01},

urldate = {2021-05-26},

journal = {Cell Reports},

volume = {29},

number = {13},

pages = {4285--4294.e5},

note = {Publisher: Elsevier},

keywords = {autism, GluN1, long-term potentiation, N1 cassette, NMDA Receptor, splicing},

pubstate = {published},

tppubtype = {article}

}