Below you will find scientific publications authored by our members or those enabled by our platform services.
2019
Siu, M T; Butcher, D T; Turinsky, A L; Cytrynbaum, C; Stavropoulos, D J; Walker, S; Caluseriu, O; Carter, M; Lou, Y; Nicolson, R; Georgiades, S; Szatmari, P; Anagnostou, E; Scherer, S W; Choufani, S; Brudno, M; Weksberg, R
Functional DNA methylation signatures for autism spectrum disorder genomic risk loci: 16p11.2 deletions and CHD8 variants Journal Article
In: Clinical Epigenetics, vol. 11, no. 1, pp. 103, 2019, ISSN: 1868-7083.
Abstract | Links | BibTeX | Tags: Autism spectrum disorder, DNA methylation, epigenetics, Genetic stratification, Genomic variants, Heterogeneity
@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}
}
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
2018
Venuto, David; Bourque, Guillaume
Identifying co-opted transposable elements using comparative epigenomics Journal Article
In: Development, Growth & Differentiation, vol. 60, no. 1, pp. 53-62, 2018.
Abstract | Links | BibTeX | Tags: comparative epigenomics, epigenetics, functional genome, genomics, transposable elements
@article{https://doi.org/10.1111/dgd.12423,
title = {Identifying co-opted transposable elements using comparative epigenomics},
author = {David Venuto and Guillaume Bourque},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/dgd.12423},
doi = {https://doi.org/10.1111/dgd.12423},
year = {2018},
date = {2018-01-01},
journal = {Development, Growth & Differentiation},
volume = {60},
number = {1},
pages = {53-62},
abstract = {The human genome gives rise to different epigenomic landscapes that define each cell type and can be deregulated in disease. Recent efforts by ENCODE, the NIH Roadmap and the International Human Epigenome Consortium (IHEC) have made significant advances towards assembling reference epigenomic maps of various tissues. Notably, these projects have found that approximately 80% of human DNA was biochemically active in at least one epigenomic assay while only approximately 10% of the sequence displayed signs of purifying selection. Given that transposable elements (TEs) make up at least 50% of the human genome and can be actively transcribed or act as regulatory elements either for their own purposes or be co-opted for the benefit of their host; we are interested in exploring their overall contribution to the “functional” genome. Traditional methods used to identify functional DNA have relied on comparative genomics, conservation analysis and low throughput validation assays. To discover co-opted TEs, and distinguish them from noisy genomic elements, we argue that comparative epigenomic methods will also be important.},
keywords = {comparative epigenomics, epigenetics, functional genome, genomics, transposable elements},
pubstate = {published},
tppubtype = {article}
}
The human genome gives rise to different epigenomic landscapes that define each cell type and can be deregulated in disease. Recent efforts by ENCODE, the NIH Roadmap and the International Human Epigenome Consortium (IHEC) have made significant advances towards assembling reference epigenomic maps of various tissues. Notably, these projects have found that approximately 80% of human DNA was biochemically active in at least one epigenomic assay while only approximately 10% of the sequence displayed signs of purifying selection. Given that transposable elements (TEs) make up at least 50% of the human genome and can be actively transcribed or act as regulatory elements either for their own purposes or be co-opted for the benefit of their host; we are interested in exploring their overall contribution to the “functional” genome. Traditional methods used to identify functional DNA have relied on comparative genomics, conservation analysis and low throughput validation assays. To discover co-opted TEs, and distinguish them from noisy genomic elements, we argue that comparative epigenomic methods will also be important.
Singh, G; Singh, V; Wang, Zi-Xuan; Voisin, G; Lefebvre, F; Navenot, J-M; Evans, B; Verma, M; Anderson, D W; Schneider, J S
Effects of developmental lead exposure on the hippocampal methylome: Influences of sex and timing and level of exposure Journal Article
In: Toxicology Letters, vol. 290, pp. 63–72, 2018, ISSN: 0378-4274.
Abstract | Links | BibTeX | Tags: Brain, Developmental exposure, DNA methylation, epigenetics, Heavy metal, Hippocampus, Lead toxicity, Sex
@article{singh_effects_2018,
title = {Effects of developmental lead exposure on the hippocampal methylome: Influences of sex and timing and level of exposure},
author = {G Singh and V Singh and Zi-Xuan Wang and G Voisin and F Lefebvre and J-M Navenot and B Evans and M Verma and D W Anderson and J S Schneider},
url = {https://www.sciencedirect.com/science/article/pii/S0378427418301085},
doi = {10.1016/j.toxlet.2018.03.021},
issn = {0378-4274},
year = {2018},
date = {2018-01-01},
urldate = {2021-05-19},
journal = {Toxicology Letters},
volume = {290},
pages = {63--72},
abstract = {Developmental lead (Pb) exposure results in persistent cognitive/behavioral impairments as well as an elevated risk for developing a variety of diseases in later life. Environmental exposures during development can result in a variety of epigenetic changes, including alterations in DNA methylation, that can influence gene expression patterns and affect the function and development of the nervous system. The present promoter-based methylation microarray profiling study explored the extent to which developmental Pb exposure may modify the methylome of a brain region, hippocampus, known to be sensitive to the effects of Pb exposure. Male and female Long Evans rats were exposed to 0 ppm, 150 ppm, 375 ppm, or 750 ppm Pb through perinatal exposures (gestation through lactation), early postnatal exposures (birth through weaning), or long-term postnatal exposures (birth through postnatal day 55). Results showed a significant contribution of sex to the hippocampal methylome and effects of Pb exposure level, with non-linear dose response effects on methylation. Surprisingly, the developmental period of exposure contributed only a small amount of variance to the overall data and gene ontology (GO) analysis revealed the largest number of overrepresented GO terms in the groups with the lowest level of exposure. The highest number of significant differentially methylated regions was found in females exposed to Pb at the lowest exposure level. Our data reinforce the significant effect that low level Pb exposure may have on gene-specific DNA methylation patterns in brain and that this occurs in a sex-dependent manner.},
keywords = {Brain, Developmental exposure, DNA methylation, epigenetics, Heavy metal, Hippocampus, Lead toxicity, Sex},
pubstate = {published},
tppubtype = {article}
}
Developmental lead (Pb) exposure results in persistent cognitive/behavioral impairments as well as an elevated risk for developing a variety of diseases in later life. Environmental exposures during development can result in a variety of epigenetic changes, including alterations in DNA methylation, that can influence gene expression patterns and affect the function and development of the nervous system. The present promoter-based methylation microarray profiling study explored the extent to which developmental Pb exposure may modify the methylome of a brain region, hippocampus, known to be sensitive to the effects of Pb exposure. Male and female Long Evans rats were exposed to 0 ppm, 150 ppm, 375 ppm, or 750 ppm Pb through perinatal exposures (gestation through lactation), early postnatal exposures (birth through weaning), or long-term postnatal exposures (birth through postnatal day 55). Results showed a significant contribution of sex to the hippocampal methylome and effects of Pb exposure level, with non-linear dose response effects on methylation. Surprisingly, the developmental period of exposure contributed only a small amount of variance to the overall data and gene ontology (GO) analysis revealed the largest number of overrepresented GO terms in the groups with the lowest level of exposure. The highest number of significant differentially methylated regions was found in females exposed to Pb at the lowest exposure level. Our data reinforce the significant effect that low level Pb exposure may have on gene-specific DNA methylation patterns in brain and that this occurs in a sex-dependent manner.
Caron, Maxime; St-Onge, Pascal; Drouin, Simon; Richer, Chantal; Sontag, Thomas; Busche, Stephan; Bourque, Guillaume; Pastinen, Tomi; Sinnett, Daniel
In: PLOS ONE, vol. 13, no. 11, pp. e0207250, 2018, ISSN: 1932-6203, (Publisher: Public Library of Science).
Abstract | Links | BibTeX | Tags: Blood, Cancers and neoplasms, Chromatin, DNA methylation, epigenetics, Histones, Human genomics, RNA sequencing
@article{caron_very_2018,
title = {Very long intergenic non-coding RNA transcripts and expression profiles are associated to specific childhood acute lymphoblastic leukemia subtypes},
author = {Maxime Caron and Pascal St-Onge and Simon Drouin and Chantal Richer and Thomas Sontag and Stephan Busche and Guillaume Bourque and Tomi Pastinen and Daniel Sinnett},
url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207250},
doi = {10.1371/journal.pone.0207250},
issn = {1932-6203},
year = {2018},
date = {2018-01-01},
urldate = {2021-05-19},
journal = {PLOS ONE},
volume = {13},
number = {11},
pages = {e0207250},
abstract = {Very long intergenic non-coding RNAs (vlincRNAs) are a novel class of long transcripts (textasciitilde50 kb to 1 Mb) with cell type- or cancer-specific expression. We report the discovery and characterization of 256 vlincRNAs from a cohort of 64 primary childhood pre-B and pre-T acute lymphoblastic leukemia (cALL) samples, of which 61% are novel and specifically expressed in cALL. Validation was performed in 35 pre-B and pre-T cALL primary samples. We show that their expression is cALL immunophenotype and molecular subtype-specific and correlated with epigenetic modifications on their promoters, much like protein-coding genes. While the biological functions of these vlincRNAs are still unknown, our results suggest they could play a role in cALL etiology or progression.},
note = {Publisher: Public Library of Science},
keywords = {Blood, Cancers and neoplasms, Chromatin, DNA methylation, epigenetics, Histones, Human genomics, RNA sequencing},
pubstate = {published},
tppubtype = {article}
}
Very long intergenic non-coding RNAs (vlincRNAs) are a novel class of long transcripts (textasciitilde50 kb to 1 Mb) with cell type- or cancer-specific expression. We report the discovery and characterization of 256 vlincRNAs from a cohort of 64 primary childhood pre-B and pre-T acute lymphoblastic leukemia (cALL) samples, of which 61% are novel and specifically expressed in cALL. Validation was performed in 35 pre-B and pre-T cALL primary samples. We show that their expression is cALL immunophenotype and molecular subtype-specific and correlated with epigenetic modifications on their promoters, much like protein-coding genes. While the biological functions of these vlincRNAs are still unknown, our results suggest they could play a role in cALL etiology or progression.