Biology subjects

Nandi, T.

Publications and source records attributed to Nandi, T..

3 recordsLinked to original sources

bioRxiv2018

Gut microbiome recovery after antibiotic usage is mediated by specific bacterial species

Dysbiosis in the gut microbiome due to antibiotic usage can persist for extended periods of time, impacting host health and increasing the risk for pathogen colonization. The specific factors associated with variability in gut microbiome recovery remain unknown. Using data from 4 different cohorts in 3 continents comprising >500 microbiome profiles from 117 subjects, we identified 20 bacterial species exhibiting robust association with gut microbiome recovery post antibiotic therapy. Functional and growth analysis showed that microbiome recovery is supported by enrichment in carbohydrate degradation and energy production capabilities. Association rule mining on 782 microbiome profiles from the MEDUSA database enabled reconstruction of the gut microbial food-web, identifying many recovery-associated bacteria (RABs) as primary colonizing species, with the ability to use both host and diet-derived energy sources, and to break down complex carbohydrates to support the growth of other bacteria. Experiments in a mouse model recapitulated the ability of RABs (Bacteroides thetaiotamicron and Bifidobacterium adolescentis) to promote microbiome recovery with synergistic effects, providing a two orders of magnitude boost to microbial abundance in early time-points and faster maturation of microbial diversity. The identification of specific microbial factors promoting microbiome recovery opens up opportunities for rationally fine-tuning pre- and probiotic formulations that prevent pathogen colonization and promote gut health.

genomics↗

bioRxiv2017

Pan-cancer study of heterogeneous RNA aberrations

We present the most comprehensive catalogue of cancer-associated gene alterations through characterization of tumor transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes project. Using matched whole-genome sequencing data, we attributed RNA alterations to germline and somatic DNA alterations, revealing likely genetic mechanisms. We identified 444 associations of gene expression with somatic non-coding single-nucleotide variants. We found 1,872 splicing alterations associated with somatic mutation in intronic regions, including novel exonization events associated with Alu elements. Somatic copy number alterations were the major driver of total gene and allele-specific expression (ASE) variation. Additionally, 82% of gene fusions had structural variant support, including 75 of a novel class called \"bridged\" fusions, in which a third genomic location bridged two different genes. Globally, we observe transcriptomic alteration signatures that differ between cancer types and have associations with DNA mutational signatures. Given this unique dataset of RNA alterations, we also identified 1,012 genes significantly altered through both DNA and RNA mechanisms. Our study represents an extensive catalog of RNA alterations and reveals new insights into the heterogeneous molecular mechanisms of cancer gene alterations.

genomics↗

bioRxiv2017

A pan cancer analysis of promoter activity highlights the regulatory role of alternative transcription start sites and their association with noncoding mutations

Most human protein-coding genes are regulated by multiple, distinct promoters, suggesting that the choice of promoter is as important as its level of transcriptional activity. While the role of promoters as driver elements in cancer has been recognized, the contribution of alternative promoters to regulation of the cancer transcriptome remains largely unexplored. Here we infer active promoters using RNA-Seq data from 1,188 cancer samples with matched whole genome sequencing data. We find that alternative promoters are a major contributor to context-specific regulation of isoform expression and that alternative promoters are frequently deregulated in cancer, affecting known cancer-genes and novel candidates. Our study suggests that a highly dynamic landscape of active promoters shapes the cancer transcriptome, opening many opportunities to further explore the interplay of regulatory mechanism and noncoding somatic mutations with transcriptional aberrations in cancer.

genomics↗