catch-up-high-throughput-upstream-pipeline-for-bulk-atac-seq-chip-seq

CATCH-UP: A High-Throughput Upstream-Pipeline for Bulk ATAC-Seq and ChIP-Seq Data

Assay for transposase-accessible chromatin (ATAC) and chromatin immunoprecipitation (ChIP), coupled with next-generation sequencing (NGS), have ...

University of Oxford

The Regional Student Group Turkey (RSG-Turkey) is officially associated with the International Society for Computational Biology (ISCB) Student Council (SC). At the RSG-Turkey, we aim to contribute to the early-career researchers in computational biology and bioinformatics fields by providing opportunities for improving their academic and technical skills in the field. Over the last ten years, we have built a well-known student-driven academic society in Turkey that organizes numerous events every year and continues to grow with over 650 current members. Celebrating the 10th anniversary of RSG-Turkey, in this communication, we share our experiences, five main lessons we learned, and the steps to establish a long-standing academic community: having a clear mission, building a robust structure, effective communication, turning challenges into opportunities, and building collaborations. We believe that our experiences can help students and academics establish long-standing communities in fast-developing areas like bioinformatics.

Lessons from a ten-year-long journey: building a student-driven computational biology society across Turkey.

The chromatin remodeller ATRX interacts with the histone chaperone DAXX to deposit the histone variant H3.3 at sites of nucleosome turnover. ATRX is known to bind repetitive, heterochromatic regions of the genome including telomeres, ribosomal DNA and pericentric repeats, many of which are putative G-quadruplex forming sequences (PQS). At these sites ATRX plays an ancillary role in a wide range of nuclear processes facilitating replication, chromatin modification and transcription. Here, using an improved protocol for chromatin immunoprecipitation, we show that ATRX also binds active regulatory elements in euchromatin. Mutations in ATRX lead to perturbation of gene expression associated with a reduction in chromatin accessibility, histone modification, transcription factor binding and deposition of H3.3 at the sequences to which it normally binds. In erythroid cells where downregulation of α-globin expression is a hallmark of ATR-X syndrome, perturbation of chromatin accessibility and gene expression occurs in only a subset of cells. The stochastic nature of this process suggests that ATRX acts as a general facilitator of cell specific transcriptional and epigenetic programmes, both in heterochromatin and euchromatin.

The chromatin remodeller ATRX facilitates diverse nuclear processes, in a stochastic manner, in both heterochromatin and euchromatin.

Understanding clonal evolution and cancer development requires experimental approaches for characterizing the consequences of somatic mutations on gene regulation. However, no methods currently exist that efficiently link high-content chromatin accessibility with high-confidence genotyping in single cells. To address this, we developed Genotyping with the Assay for Transposase-Accessible Chromatin (GTAC), enabling accurate mutation detection at multiple amplified loci, coupled with robust chromatin accessibility readout. We applied GTAC to primary acute myeloid leukemia, obtaining high-quality chromatin accessibility profiles and clonal identities for multiple mutations in 88% of cells. We traced chromatin variation throughout clonal evolution, showing the restriction of different clones to distinct differentiation stages. Furthermore, we identified switches in transcription factor motif accessibility associated with a specific combination of driver mutations, which biased transformed progenitors toward a leukemia stem cell-like chromatin state. GTAC is a powerful tool to study clonal heterogeneity across a wide spectrum of pre-malignant and neoplastic conditions.

E. Ravza Gur

MRC Molecular Haematology Unit,
MRC Weatherall Institute of Molecular Medicine,
MRC WIMM Centre for Computational Biology,
MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine,
MRC WIMM Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine

University of Oxford

CATCH-UP: A High-Throughput Upstream-Pipeline for Bulk ATAC-Seq and ChIP-Seq Data