Over the last two decades, large scale epigenomic studies showed that aberrant epigenomic landscape is an essential molecular feature of cancer cells and established as a hallmark of cancer. Epigenetic dysregulation in cancer could arise due to genetic and epigenetic changes of the proteins involved in epigenetic modifications. The goal of my study is to characterize dysregulated epigenomic states and understand their mechanisms in two different lymphoid leukemias e.g., T-cell acute lymphoblastic leukemia (T-ALL) and B-cell chronic lymphocytic leukemia (CLL). Using integrative analysis of multiple layers of epigenomic datasets, my analysis identified disease specific enhancers which are associated with proto-oncogene activation in those leukemias. I identified pathogenic enhancers are established and maintained by the runt related transcription factor 1 (RUNX1) in leukemia. To leverage the valuable epigenetic datasets in clinical subtypes of CLL, I developed a computational pipeline, CRIS, to classify CLL patients based on somatic hypermutations of immunoglobulin variable gene using RNA-seq.
- Raw sequencing data is available via accession number GSE99706.
- Processed files: bed files, super-enhanceers, differentially expressed genes and RPKM matrix of gene expression.
- Raw sequencing data is available at CEMT and BLUEPRINT.
- Pipeline: https://github.com/Rashedul/CRIS
- Raw sequencing data is available at CEMT and BLUEPRINT.
- Processed files: bed files, super-enhanceers, differentially expressed genes and RPKM matrix of gene expression.
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Rashedul Islam, Jonathan Steif, Misha Bilenky, Annaïck Carles, Alireza Heravi-Moussavi, Sitanshu Gakkhar, Andrew P Weng, Joseph M Connors, Martin Hirst. Integrative analysis of aberrant epigenomic landscape in chronic lymphocytic leukemia. Undergoing Submission as part of IHEC Consortium Package Companions, 2024.
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Rashedul Islam, Catherine E Jenkins, Qi Cao, Jasper Wong, Misha Bilenky, Annaïck Carles, Michelle Moksa, Andrew P Weng, Martin Hirst. RUNX1 colludes with NOTCH1 to reprogram chromatin in T-cell acute lymphoblastic leukemia. iScience, 2023 June, 26(6):106795..
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Xuehai Wang, Michael Nissen, Deanne Gracias, Manabu Kusakabe, Guillermo Simkin, Aixiang Jiang, Gerben Duns, Clementine Sarkozy, Laura Hilton, Elizabeth Chavez, Gabriela Segat, Rachel Wong, Jubin Kim, Tomohiro Aoki, Rashedul Islam, Christina May, Stacy Hung, Kateryna Tyshchenko, Ryan Brinkman, Martin Hirst, Aly Karsan, Ciara Freeman, Laurie Sehn, Ryan Morin, Andrew Roth, Kerry Savage, Jeffrey Craig, Sohrab Shah, Christian Steidl, David W Scott, and Andrew Weng. Single-cell profiling reveals a memory B cell-like subtype of follicular lymphoma with increased transformation risk. Nature Communications, 2022 Nov; 13(1):6772.
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Rashedul Islam, Misha Bilenky, Andrew P. Weng, Joseph M. Connors, Martin Hirst. CRIS: Complete Reconstruction of Immunoglobulin V-D-J Sequences from RNA-seq data. Bioinformatics Advances, vbab021, September 2021.
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Catherine E. Jenkins, Samuel Gusscott, Rachel J. Wong, Olena O. Shevchuk, Gurneet Rana, Vincenzo Giambra, Kateryna Tyshchenko, Rashedul Islam, Martin Hirst, Andrew P. Weng. RUNX1 promotes cell growth in human T-cell acute lymphoblastic leukemia by transcriptional regulation of key target genes. Experimental Hematology. August 2018; 64:84-96.