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Hyacinthe, J.

Publications and source records attributed to Hyacinthe, J..

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EpiATLAS - a reference for human epigenomic research

The sequence of the human genome provides a foundation for understanding cellular processes in health and disease1. The organisation of this primary genetic information into cell-specific structure and function is critical to understanding the cell type-specific interpretation and execution of the genome. Epigenetic processes are essential for packaging and higher-level functional organisation of the genome, and changes therein are increasingly recognised as contributors to human disease. Building on primary data generated by multinational consortia, the International Human Epigenome Consortium2 (IHEC) has uniformly processed a collection of more than 2000 comprehensive human reference epigenomes, collectively referred to as EpiATLAS. This effort involved the development of standardised molecular and bioinformatics protocols, metadata models, and analytical tools to manage, integrate, display, and share vast amounts of epigenomic data. This includes the creation of a publicly available Epigenome Reference Registry, which provides a system for accessing protected human subject datasets and facilitates open searching of de-identified samples and experimental data. The integrated EpiATLAS ecosystem and its comprehensive human reference epigenome maps provide an unprecedented resource for the biosciences, expanding the annotated epigenomic landscape while uncovering previously unappreciated relationships among regulatory layers and revealing how epigenetic inputs underpin fundamental cellular functions and disease associations.

genomics↗

TEExplorer: A Web Portal to Investigate TE-Epigenome Associations Across Human Cell Types

Approximately half of the human genome is derived from transposable elements (TEs) and several studies support the involvement of TEs in genome regulation in development, immunity and disease. We previously leveraged 4614 ChIP-seq samples from the International Human Epigenome Consortium (IHEC) EpiATLAS dataset and did a comprehensive analysis of the relationship between TEs and 6 histone marks across 57 human cell types. However, with over 6 million measurements of TE / histone mark / cell type enrichment, it was challenging to navigate the results and it was not possible to integrate them with user data. To address this, we developed a web tool, TEExplorer, which makes available TE overlaps and enrichments in an accessible and intuitive manner. The tool presents an interactive view of TE families and subfamilies, with their overlap and enrichments across histone marks and cell types. Finally, the tool allows users to upload their own ChIP-seq BED file to obtain the TE overlap and enrichment relative to random controls and compare their data with the EpiATLAS dataset. With TEExplorer, researchers with an interest in a particular TE family or subfamily, histone mark, or cell type, or those bringing their own ChIP-seq dataset, can dynamically explore and contrast hundreds of associations found within the large EpiATLAS dataset. AvailabilityOnline portal: https://teexplorer.c3g.sd4h.ca

genomics↗

Transposable elements impact the regulatory landscape through cell type specific epigenomic associations

Transposable elements (TEs) are DNA sequences able to create copies of themselves within the genome. Despite their limited expression due to silencing, TEs still manage to impact the host genome. For instance, some TEs have been shown to act as cis-regulatory elements and be co-opted in the human genome. This highlights that the contributions of TEs to the host might come from their relationship with the epigenome rather than their expression. However, a systematic analysis that relates TEs in the human genome directly with chromatin histone marks across distinct cell types remains lacking. Here we leverage a new dataset from the International Human Epigenome Consortium with 4867 uniformly processed ChIP-seq experiments for 6 histone marks across 175 annotated cell labels and show that TEs have drastically different enrichments levels across marks. Overall, we find that TEs are generally depleted in H3K9me3 histone modification, except for L1s, while MIRs were highly enriched in H3K4me1, H3K27ac and H3K27me3 and Alus were enriched in H3K36me3. Furthermore, we present a generalised profile of the relationship between TEs enrichment and TE age which reveals a few TE families (Alu, MIR, L2) as diverging from expected dynamics. We also find significant differences in TE enrichment between cell types and that in 20% of the cases, these enrichments were cell-type specific. Moreover, we report that at least 4% of cell types-histone-TE combinations featured significant differences in enrichment between healthy and cancer samples. Notably, we identify 456 cell type-histone-TE triplets with strong cell-type specific enrichments. We show that many of these triplets are associated with relevant biological processes and genes expressed in the relevant cell type. These results further support a role for TE in genome regulation and highlight novel associations between TEs and histone marks across cell types.

genomics↗