Biology subjects

Chateigner, A.

Publications and source records attributed to Chateigner, A..

4 recordsLinked to original sources

bioRxiv2019

How to maintain a high virulence: evolution of a killer in hosts of various susceptibilities.

Pathogens should evolve to avirulence. However, while baculoviruses can be transmitted through direct contact, their main route of infection goes through the death and liquefaction of their caterpillar hosts and highly virulent strains still seem to be advantaged through infection cycles. Furthermore, one of them, Autographa californica multiple nucleopolyhedrovirus, is so generalist that it can infect more than 100 different hosts.\n\nTo understand and characterize the evolutionary potential of this virus and how it is maintained while killing some of its hosts in less than a week, we performed an experimental evolution starting from an almost natural isolate of AcMNPV, known for its generalist infection capacity. We made it evolve on 4 hosts of different susceptibilities for 10 cycles and followed hosts survival each day. We finally evaluated whether the generalist capacity was maintained after evolving on one specific host species and tested an epidemiological model through simulations to understand how.\n\nFinally, on very highly susceptible hosts, transmission-virulence trade-offs seem to disappear and the virus can maximize transmission and virulence. When less adapted to its host, the pathogens virulence has not been modified along cycles but the yield was increased, apparently through an increased transmission probability and an increased latent period between exposition and infection.

evolutionary biology↗

bioRxiv2019

Gene Expression Predictions and Networks in Natural Populations Supports the Omnigenic Theory

Recent literature on the differential role of genes within networks distinguishes core from peripheral genes. If previous works have shown contrasting features between them, whether such categorization matters for phenotype prediction remains to be studied. We sequenced RNA in a Populus nigra collection and built co-expression networks to define core and peripheral genes. We found that cores were more differentiated between populations than peripherals while being less variable, suggesting that they have been constrained through potentially divergent selection. We also showed that while cores were overrepresented in a subset of genes deemed important for trait prediction, they did not systematically predict better than peripherals or even random genes. Our work is the first attempt to assess the importance of co-expression network connectivity in phenotype prediction. While highly connected core genes appear to be important, they do not bear enough information to systematically predict better quantitative traits than other gene sets.

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

Motif Disruption Domains Lead To Cancer Gene Expression Rewiring

Somatic mutations accumulate in non-coding regions of the genome during tumorigenesis, but their functional characterization presents a challenge. Somatic non-coding mutations rarely overlap among patients, which necessitates large sample sizes to detect associations. We analysed somatic mutations called from whole-genome sequencing (WGS) and RNA sequencing (RNAseq) from 3000 tumors across the Pan-Cancer Analysis of Whole Genomes to identify and functionally characterize mutation accumulation and its impact on gene dysregulation in cancer. We identified 1.5 million motif disruption domains (MDDs) across 40 cancer types, which we characterized as pan-cancer targets for recurrent mutation accumulation. These MDDs deregulate gene expression in cancer-specific and pan-cancer patterns by disrupting transcription factor binding sites in regulatory and insulator elements. Disruption is most recurrent across individuals at MDDs in conserved open chromatin, revealing potential drivers. This accumulation of somatic variants targeting regulatory and structural elements in MDDs generates gene expression dysregulation during tumorigenesis.

cancer biology↗