Search bioRxiv⌕ Search

Biology subjects

Satsangi, D.

Publications and source records attributed to Satsangi, D..

2 recordsLinked to original sources

A draft Arab pangenome reference

Pangenomes represent a significant shift from relying on a single reference sequence to a robust set of assemblies, Arab populations remain significantly underrepresented; hence, we present the first Arab Pangenome Reference (APR) utilizing 53 individuals of diverse Arab ethnicities. We assembled nuclear and mitochondrial pangenomes using 35.27X high-fidelity long reads, 54.22X ultralong reads and 65.46X Hi-C reads yielded contiguous haplotype-phased de novo assemblies of exceptional quality, with an average N50 of 124.28 Mb. We discovered 111.96 million base pairs of novel euchromatic sequences absent from existing human pangenomes, the T2T-CHM13, GRCh38 reference human genomes, and other public datasets. We identified 8.94 million population-specific small variants and 235,195 structural variants within the Arab pangenome. We detected 883 gene duplications including 15.06% associated with recessive diseases and 1,436 bp of novel mitochondrial pangenome sequence. Our study provides a valuable resource for future genomic medicine initiatives in Arab population and other global populations.

genomics↗

Cell-free chromatin particles activate immune checkpoints in human T cells: Implications for cancer therapy

Immune checkpoint blockade is an exciting breakthrough in cancer therapy, but how immune checkpoints are activated is unknown. We have earlier reported that cell-free chromatin particles (cfChPs) that circulate in the blood, or those that are released locally from dying cells, are readily internalized by healthy cells with biological consequences. Here we show that treatment of human lymphocytes with cfChPs isolated from sera of cancer patients led to marked activation of immune checkpoints viz. PD-1, CTLA-4, LAG-3, NKG2A, and TIM-3. Concurrently activated were stress-related markers cJun, cFos, JunB, FosB, NF[Kcy]B, and EGR1. The above immune checkpoints were also activated when lymphocytes were treated with cfChPs released from dying HeLa cells; the latter could be abrogated by three cfChPs deactivating agents. These results suggest that immune checkpoints are activated by lymphocytes as stress response to cfChPs. Simultaneous downregulation of multiple immune checkpoints may herald a new approach to immunotherapy of cancer. Statement of SignificanceWe show that cell-free chromatin particles (cfChPs) that circulate in the blood of cancer patients, or those released from dying cancer cells, simultaneously activate five immune checkpoints as a stress response by human lymphocytes. Activation of checkpoints was abrogated by cfChPs deactivating agents suggesting a novel approach to cancer treatment.

immunology↗