Biology subjects

Demars, J.

Publications and source records attributed to Demars, J..

6 recordsLinked to original sources

bioRxiv2025

Neural network-based cross-species chromatin annotation goes beyond sequence conservation

Analogous to the Encyclopedia of DNA Elements (ENCODE) project, the Functional Annotation of ANimal Genomes (FAANG) consortium has produced chromatin annotations for domesticated animals, albeit in smaller amounts. Although acquiring experimental data is more accessible and affordable for many species, human and mouse organisms will remain the reference. Classical methods based on sequence conservation can be used to infer missing annotations, but are inappropriate for non-conserved sequences. While regulatory sequences share low to moderate conservation, they have retained their regulatory function during the evolution process. Here, we take advantage of three neural networks (DeepBind, DeepSEA, and Enformer) trained with human and mouse ENCODE data to infer chromatin annotations (transcription factors binding, chromatin accessibility, and histone marks) in cattle, pig, chicken, and European seabass. For this purpose, we comprehensively assessed the quality of predictions using experimental data from FAANG, through AUC-ROC and AUC-PR metrics. Our results showed similar predictions for various annotations in mammals and chicken, with AUC-PR ranging from 0.157 to 0.765 for H3K4me1 and H3K4me3, respectively, but lower in fish. Further analyses focused on pigs highlighted (i) accurate predictions even for non-conserved sequences, and (ii) variable predictions depending on genomic feature annotations. Our results advocate the widespread use of human-trained neural networks as a first step in cross-species genome annotation before training species-specific models.

genomics↗

bioRxiv2025

The effect of environmental enrichment on immune cell DNA methylation profiles depends on the parity of sows.

The aim of this study was to identify epigenetic markers that reflected positive affective states in multiparous pregnant sows. The animals were housed during gestation in either a conventional (C) environment (2.4 m{superscript 2} per sow), featuring a concrete slatted floor and minimal enrichment, or in an enriched (E) environment (3.5 m{superscript 2} per sow) with deep straw bedding. Peripheral blood mononuclear cells (PBMCs) were isolated at day 98 of gestation (G98) and day 12 of lactation (L12) for genomic DNA extraction and reduced representation bisulfite sequencing (RRBS). Significant effects of individual class of parity (low-parity (LP) versus high-parity (HP)) were observed with the identification of 1,358 and 680 differentially methylated cytosines (DMCs) at G98 and L12, respectively. Interestingly, some of them are organized into differentially methylated regions (DMRs). Some DMRs colocalized with or near a gene and displayed a continuous methylation distribution (44 at G98 and 15 at L12 including 4 in common): 5 targeted genes are related to epigenetic regulation (DNMT3A, KDM8, HDAC4, SIRT2 and U2) and 12 to immune function (CD2, CD5, CAMK4, SECTM1, URODL1, CMIP, SEC14L1, SKI, TNFRSF1B, CCND3, SGK1, PACS1). These results suggested a true epigenetic impact of parity class on individual immunity. Considering the two parity classes separately, a minor effect of environmental enrichment was observed (at G98: 60 and 42 DMCs; at L12: 35 and 81 DMCs, in the LP and HP groups, respectively). Remarkably, some DMC-associated genes had previously been linked to affective states in humans. In conclusion, unexpected DNA methylation changes associated with parity class were identified, suggesting a genome adaptation during reproductive life and modifying the response to housing conditions. Furthermore, specific CpG sites emerged as potential biomarkers of positive affective states in pigs. HighlightsO_LIThis study revealed a substantial impact of the genetic background of sows on DNA methylation patterns, emphasizing the need to account for genetic factors when analysing epigenetic data. C_LIO_LIParity, which was confounded with the age of the sows in this study, significantly influenced DNA methylation, even among multiparous sows, highlighting the importance of this factor in modulating epigenetic mechanisms in immune cells. C_LIO_LIWe observed minor differences in the effects of environmental enrichment on DNA methylation profiles, which differed depending on the parity group. C_LIO_LIWe suggest a short list of possible biomarkers with biological meaning responding to environmental enrichment. C_LI

genomics↗

bioRxiv2025

An extensive and unbiased genome-wide scan for parent-of-origin expressed genes in the pig clarifies the conservation landscape of genomic imprinting

Genomic imprinting, a mechanism resulting in parent-of-origin expression of genes through epigenetic regulation, intersects with a broad range of biological fields including evolution, molecular genetics and epigenetics and determinism of complex traits. Although next generation sequencing technologies enable nowadays to detect imprinted genes in a genome-wide manner, a wide spectrum of this phenomena is evaluated only in humans and mice. Here, we propose to map genes showing a parental expression bias in hypothalamus, muscle and placenta in piglets around birth using an extensive and unbiased strategy that relied on reciprocal crosses, genetics reconstruction of parental phases after imputation and statistical analyses discriminating parent-of-origin from allele-specific expression. We detected 440 unique genes with a weak to exclusive parental expression bias including 114 unique genes with an imbalance ratio above 25:75. About thirty imprinted genes are common to human and/or mice and an equivalent number is shared between tissues, suggesting an overall weak conservation landscape of genomic imprinting. Interestingly, we identified novel parent-of-origin expressed genes involved in neurodevelopmental (PITRM1, Pitrilysin Metallopeptidase 1) and fetal growth (FAM20B, Glycosaminoglycan Xylosylkinase and POU6F2, POU Class 6 Homeobox 2) functions. In addition, deeper analyses of specific loci likely highlighted lineage-specific imprinted genes such as a Zinc Finger Protein 300-like gene as well as specific imprinted isoforms of COPG2 (COPI Coat Complex Subunit Gamma 2), a gene showing conflicting data in the literature. Altogether, our results bring pig as the most comprehensively and exhaustively documented species for genomic imprinting after human and mice organisms. A weak conservation of this mechanism across species and tissues suggested a distinction between a small number of core imprinted genes and others parent-of-origin expressed genes that seemed subjected to evolutionary forces for acquiring their imprinting status either in a lineage-specific or tissue-specific manner.

genomics↗

bioRxiv2023

A methyl-seq tool to capture genomic imprinted loci

Genomic imprinting represents an original model of epigenetic regulation resulting in a parent-of-origin expression. Despite the critical role of imprinted genes in mammalian growth, metabolism and neuronal function, there is no molecular tool specifically targeting them for a systematic evaluation. Here, we optimized and compared to bisulfite-based standard a novel methyl-seq system to capture 165 candidate regions for genomic imprinting and ultimately detect parent-of-origin methylation, the main hallmark of imprinting.

genomics↗

bioRxiv2022

Stronger transcriptomic response to feed intake in the duodenum of pig with high feed efficiency from a divergent selection experiment

Feed efficiency is a trait of interest in pigs as it contributes to lowering the ecological and economical costs of pig production. A divergent genetic selection experiment from a Large White pig population was performed for 10 generations, leading to pig lines with relative low-(LRFI, more efficient) and high-(HRFI, less efficient) residual feed intake (RFI). Feeding behaviour and metabolic differences have been previously reported between the two lines. We hypothesised that part of these differences could be related to differential sensing and absorption of nutrients in the proximal intestine. Here we investigated the duodenum transcriptome and DNA methylation profiles comparing overnight fasting with ad libitum feeding in LRFI and HRFI pigs (n=24). We identified 1,106 differentially expressed genes between the two lines, notably affecting pathways of the transmembrane transport activity and related to mitosis or chromosome separation. The LRFI line showed a greater transcriptomic response to feed intake, with 2,222 differentially expressed genes before and after a meal, as compared to 61 differentially expressed genes in the HRFI line. Feed intake affected genes from both anabolic and catabolic pathways in the pig duodenum, such as rRNA production and autophagy. We noted that several nutrient transporter and tight junction genes were differentially expressed between lines and/or by short term feed intake. We also identified 409 differentially methylated regions in the duodenum mucosa between the two lines, while this epigenetic mark was less affected by feeding. However most of the differentially expressed genes were not associated with proximal changes in DNA methylation profiles. Altogether, our findings highlighted that the genetic selection for feed efficiency in pigs changed the transcriptome profiles of the duodenum, and notably its response to feed intake, suggesting key roles for this proximal gut segment in mechanisms underlying feed efficiency.

genomics↗

bioRxiv2021

A genome-wide epistatic network underlies the molecular architecture of continuous color variation of body extremities: a rabbit model

Deciphering the molecular architecture of coat coloration for a better understanding of the biological mechanisms underlying pigmentation still remains a challenge. We took advantage of a rabbit French experimental population in which both a pattern and a gradient of coloration from white to brown segregated within the himalayan phenotype. The whole experimental design was genotyped using the high density Affymetrix(R) AxiomOrcun SNP Array and phenotyped into 6 different groups ordered from the lighter to the darker. Genome-wide association analyses pinpointed an oligogenic determinism, under recessive and additive inheritance, involving genes already known in melanogenesis (ASIP, KIT, MC1R, TYR), and likely processed pseudogenes linked to ribosomal function, RPS20 and RPS14. We also identified (i) gene-gene interactions through ASIP:MC1R affecting light cream/beige phenotypes while KIT:RPS responsible of dark chocolate/brown colors and (ii) a genome-wide epistatic network involving several others coloration genes such as POT1 or HPS5. Finally, we determined the recessive inheritance of the English spotting phenotype likely involving a copy number variation affecting at least the end of the coding sequence of the KIT gene. Our analyses of coloration as a continuous trait allowed us to go beyond much of the established knowledge through the detection of additional genes and gene-gene interactions that may contribute to the molecular architecture of the coloration phenotype. Moreover, the characterization of a network including genes that contribute to melanogenesis and pigmentation, two processes affected in various human disorders, shows the potential interest of our rabbit model for transversal studies.

genetics↗