Biology subjects

Arrigo, N.

Publications and source records attributed to Arrigo, N..

4 recordsLinked to original sources

bioRxiv2022

A deep learning approach for improved detection of homologous recombination deficiency from shallow genomic profiles

Homologous Recombination Deficiency (HRD) is a predictive biomarker of poly-ADP ribose polymerase 1 inhibitors (PARPi) response. Most HRD detection methods are based on genome wide enumeration of scarring events and require deep genome sequence profiles (> 30x). The cost and workflow-specific biases introduced by these genome profiling methods currently limits clinical adoption of HRD testing. We introduce the Genomic Integrity Index (GII), a Convolutional Neuronal Network, that leverages features from low pass (1x) Whole Genome Sequencing data to distinguish HRD positive and negative samples. In a cohort of 230 ovarian and breast cancer, we found GII supports accurate stratification of samples yielding results that are highly concordant with state-of-the-art HRD detection methods (0.865<AUC<0.996) which require 50x deeper coverage. We conclude that the deep learning framework supporting GII allows accurate detection of HRD from shallow genome profiles, reducing biases and data generation costs making it uniquely suited for clinical applications.

cancer biology↗

bioRxiv2021

Mutational hotspot in the SARS-CoV-2 Spike protein N-terminal domain conferring immune escape potential

Global efforts are being taken to monitor the evolution of SARS-CoV-2, aiming at early identification of mutations with the potential of increasing viral infectivity or virulence. We report a striking increase in the frequency of recruitment of diverse substitutions at a critical residue (W152), positioned in the N-terminal domain (NTD) of the Spike protein, observed repeatedly across independent phylogenetic and geographical contexts. We investigate the impact these mutations might have on the evasion of neutralizing antibodies. Finally, we uncover that NTD is a region exhibiting particularly high frequency of mutation recruitments, suggesting an evolutionary path on which the virus maintains optimal efficiency of ACE2 binding combined with the flexibility facilitating the immune escape.

genomics↗

bioRxiv2018

Polyploid plants have faster rates of multivariate climatic niche evolution than their diploid relatives

Whole genome duplication is an important evolutionary process in plants. In contrast to other speciation mechanisms, polyploid species begin with substantial postzygotic reproductive isolation from progenitors while being sympatric with one or both. These nascent polyploid species often go extinct due to ecological and evolutionary genetic obstacles. Interestingly, polyploid species appear to quickly occupy different geographic distributions and ecological niches than their diploid progenitors. Using biogeographic data from polyploid and diploid species representing 49 genera of vascular plants, we tested whether climatic niches of polyploid species evolve faster than their diploid relatives. We found polyploid species often have less climatic overlap than expected with diploid progenitors. Consistent with this pattern, we estimated that the climatic niches of polyploid plants consistently evolved faster than the niches of diploid relatives. Our results indicate ecological niche differentiation is important for polyploid establishment, and suggest ecological differentiation is important for speciation processes more widely.\n\nStatement of AuthorshipAB and MS conceived of project, AB and NA generated the dataset, AB and HM performed analyses, AB and MS cowrote manuscript.\n\nData Accessibility StatementUpon acceptance all necessary R scripts, data, and files supporting the results will be archived on FigShare with the data DOI included at the end of the article.

evolutionary biology↗

bioRxiv2017

DiscoSnp-RAD: de novo detection of small variants for population genomics

We present an original method to de novo call variants for Restriction site associated DNA Sequencing (RAD-Seq). RAD-Seq is a technique characterized by the sequencing of specific loci along the genome, that is widely employed in the field of evolutionary biology since it allows to exploit variants (mainly SNPs) information from entire populations at a reduced cost. Common RAD dedicated tools, as STACKS or IPyRAD, are based on all-versus-all read comparisons, which require consequent time and computing resources. Based on the variant caller DiscoSnp, initially designed for shotgun sequencing, DiscoSnp-RAD avoids this pitfall as variants are detected by exploring the De Bruijn Graph built from all the read datasets. We tested the implementation on RAD data from 259 specimens of Chiastocheta flies, morphologically assigned to 7 species. All individuals were successfully assigned to their species using both STRUCTURE and Maximum Likelihood phylogenetic reconstruction. Moreover, identified variants succeeded to reveal a within species structuration and the existence of two populations linked to their geographic distributions. Furthermore, our results show that DiscoSnp-RAD is at least one order of magnitude faster than state-of-the-art tools. The overall results show that DiscoSnp-RAD is suitable to identify variants from RAD data, and stands out from other tools due to his completely different principle, making it significantly faster, in particular on large datasets.\n\nLicenseGNU Affero general public license\n\nAvailabilityhttps://github.com/GATB/DiscoSnp\n\nContactjeremy.gauthier@inria.fr

bioinformatics↗