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• DNA Replication Speed controls Epigenome Integrity and T Cell Fate

  Epigenetic mechanisms maintain cellular identities by enforcing stable, cell type-specific transcriptional programs while also allowing regulated plasticity for adaptations to environmental cues like differentiation signals. Dysregulation of this dual capacity has been linked to cancer and chronic inflammation, with the regulatory mechanisms remaining poorly understood. Here, we identify DNA replication speed as a physiological regulator controlling epigenome stability and plasticity. Using T-lymphocytes as a model, we demonstrate that fast DNA replication speed impaired epigenome stability, causing DNA methylation maintenance errors at cell type-specific enhancers and heterochromatin, ultimately leading to compromised cell function. However, accelerated DNA replication speed supported epigenome plasticity during differentiation, promoting successful cell-type transitions

  Study EGAS50000001273

• Single-nuclei histone modification profiling of the adult human central nervous system unveils epigenetic memory of developmental programs

  Here, we profile the adult human CNS from distinct regions, sex and ages, for chromatin accessibility at the single-nuclei level. Tissue was collected from 20 different donors (10 male, 10 female) within the ages of 34 to 74 years old. Each donor donated fresh frozen white matter from the following three tissue regions: primary motor cortex (Brodmann area 4, BA4), arbor vitae cerebelli (CB) and fasciculi cuneatus and gracilis from and cervical spinal cord (CSC). Tissue was processed semi-randomly, ensuring that each batch of experiments had a representation of both sexes and all three tissue regions. Completed libraries were again randomly multiplexed during sequencing to minimize batch effects.

  Study EGAS50000000283

• A Genomics-Driven Artificial Intelligence-Based Model Classifies Breast Invasive Lobular Carcinoma and Discovers CDH1 Inactivating Mechanisms

  We developed an artificial intelligence (AI)-model applied to histological images using CDH1 biallelic mutations, pathognomonic for breast invasive lobular carcinoma (ILC), as ground truth. We evaluated the performance of the AI-model to predict the presence of CDH1 biallelic mutations and to diagnose ILC. Subsequently, we investigated the molecular underpinning cases of predicted by the model to harbor a CDH1 biallelic mutations but lacking these alterations according to targeted sequencing. Among this analyses, we subjected to whole genome sequencing (WGS) one ILC case lacking CDH1 biallelic mutations by targeted sequencing and lacking CDH1 promoter methylation to determine the molecular basis of its lobular phenotype.

  Study EGAS50000000485

• A73044B

  Whole genome sequencing for single cells for library A73044B 2085 cells; filetype=bam

  Dataset EGAD00001007101

• A73047D

  Whole genome sequencing for single cells for library A73047D 2091 cells; filetype=bam

  Dataset EGAD00001007102

• A95633B

  Whole genome sequencing for single cells for library A95633B 2259 cells; filetype=bam

  Dataset EGAD00001007104

• A96115A

  Whole genome sequencing for single cells for library A96115A 1635 cells; filetype=bam

  Dataset EGAD00001007111

• A96193B

  Whole genome sequencing for single cells for library A96193B 2410 cells; filetype=bam

  Dataset EGAD00001007118

• A96240B

  Whole genome sequencing for single cells for library A96240B 1683 cells; filetype=bam

  Dataset EGAD00001007122

• A95623A

  Whole genome sequencing for single cells for library A95623A 1897 cells; filetype=bam

  Dataset EGAD00001007607

• A95668B

  Whole genome sequencing for single cells for library A95668B 1905 cells; filetype=bam

  Dataset EGAD00001007609

• A95720A

  Whole genome sequencing for single cells for library A95720A 1467 cells; filetype=bam

  Dataset EGAD00001007613

• A96190A

  Whole genome sequencing for single cells for library A96190A 1833 cells; filetype=bam

  Dataset EGAD00001007620

• A96233B

  Whole genome sequencing for single cells for library A96233B 1601 cells; filetype=bam

  Dataset EGAD00001007623

• A98234B

  Whole genome sequencing for single cells for library A98234B 1600 cells; filetype=bam

  Dataset EGAD00001007627

• A98304A

  Whole genome sequencing for single cells for library A98304A 1560 cells; filetype=bam

  Dataset EGAD00001007636

• A108851B

  Whole genome sequencing for single cells for library A108851B 1681 cells; filetype=bam

  Dataset EGAD00001007596

• A108870A

  Whole genome sequencing for single cells for library A108870A 1795 cells; filetype=bam

  Dataset EGAD00001007598

• A95724B

  Whole genome sequencing for single cells for library A95724B 581 samples; filetype=bam

  Dataset EGAD00001008230

• A96172A

  Whole genome sequencing for single cells for library A96172A 1476 samples; filetype=bam

  Dataset EGAD00001008240

• A95724A

  Whole genome sequencing for single cells for library A95724A 503 samples; filetype=bam

  Dataset EGAD00001008229

• A96146A

  Whole genome sequencing for single cells for library A96146A 1195 samples; filetype=bam

  Dataset EGAD00001008233

• A96149B

  Whole genome sequencing for single cells for library A96149B 1792 samples; filetype=bam

  Dataset EGAD00001008235

• A96162B

  Whole genome sequencing for single cells for library A96162B 1316 samples; filetype=bam

  Dataset EGAD00001008238

• A96172B

  Whole genome sequencing for single cells for library A96172B 1694 samples; filetype=bam

  Dataset EGAD00001008241