Biology subjects

Verneret, M.

Publications and source records attributed to Verneret, M..

4 recordsLinked to original sources

bioRxiv2024

Particular sequence characteristics induce bias in the detection of polymorphic transposable element insertions

Transposable elements (TEs) have an important role in genome evolution but are challenging for bioinformatics detection due to their repetitive nature and ability to move and replicate within genomes. New sequencing technologies now enable the characterization of nucleotide and structural variations within species. Among them, TE polymorphism is critical to identify as it may influence species adaptation or trigger diseases. Despite the development of numerous bioinformatic programs, identifying the most effective tool is challenging due to non-overlapping results and varying efficiency across studies. Benchmarking efforts have highlighted some of the limitations of these tools, often evaluated on either real or simulated data. However, real data may be incomplete or contain unannotated TEs, while simulated data may not accurately reflect real genomes. This study introduces a simulation method generating data based on real genomes to control all genomic parameters. Evaluating several TE polymorphic detection tools using data from Drosophila melanogaster and Arabidopsis thaliana, our study investigates factors like copy size, sequence divergence, and GC content that influence detection efficiency. Our results indicate that only a few programs perform satisfactorily and that all are sensitive to TE and genomic characteristics that may differ according to the species considered. Using Bos taurus population data as a case study to identify polymorphic LTR-retrotransposon insertions, we found low-frequency insertions particularly challenging to detect due to a high number of false positives. Increased sequencing coverage improved sensitivity but reduced precision. Our work underscores the importance of selecting appropriate tools and thresholds according to the specific research questions.

bioinformatics↗

bioRxiv2024

Association between genetic clades and cancer prevalence suggested by French-wide study of oncogenic small ruminant beta-retroviruses diversity

ENTV (Enzootic Nasal Tumor Virus) and JSRV (Jaagsiekte Sheep Retrovirus) are {beta}-retroviruses responsible for respiratory cancers in sheep and goats. In this study, we analyzed the genetic features of the sheep and goat {beta}-retrovirus (29 JSRV and 24 ENTV strains) circulating in France to identify molecular signatures associated with disease severity in flocks. We developed a highly specific PCR to amplify and sequence exogenous targeted regions or near full length proviruses based on limited discriminating motifs along their genomes. The phylogenetic reconstructions based on the LTR and env regions suggest that one major strain is circulating on the French territory for ENTV-1 and ENTV-2 while not clustering with already published Spanish, Canadian or Chinese strains. JSRV strains circulating in French sheep flocks were distributed in 2 distinct genetic clades clustering with sequences originating from North America, Africa and United-Kingdom. JSRV clade I was found to be associated with a higher incidence of cancer in French flocks. Specific motifs spanning the entire JSRV genome particularly in the LTRs and in the intracytoplasmic domain of the envelope were detected between the two genetic subtypes. This work represents the first nationwide study describing the circulation of the three closely related {beta}-oncogenic retrovirus JSRV, ENTV-1 and ENTV-2 in French sheep and goat flocks. Better characterization of strain genetics is a critical step in monitoring circulating {beta} retrovirus, especially those associated with higher cancer incidence in small ruminants.

pathology↗

bioRxiv2024

A genome-wide study of ruminants reveals two endogenous retrovirus families still active in goats

BackgroundEndogenous retroviruses (ERV) are traces of ancestral retroviral germline infections that constitute a significant portion of mammalian genomes and function as LTR-retrotransposons. ERVs remain understudied in ruminants and usually focus on specific families, highlighting a need for comprehensive and thorough exploration of the ERV landscape in these species. ResultsWe characterized 23 de novo Class I and II ERV families across four reference assemblies of domestic and wild sheep and goats, and one assembly of cattle. Among these families, 15 were shared by the five ruminant species, while six were exclusive to small ruminants and two were exclusive to cattle. The presence of these families in other ruminant species revealed multiple endogenization events over 40 million years. We identified a total of 113,812 ERV insertions across the five genomes, representing between 0.5 and 1% of their genomes. Solo-LTRs account for 84.5% of the annotated copies demonstrating that most of the ERVs are relics of past events. Although Class I ERVs showed similar sequence divergence landscapes between species, Class II ERVs displayed contrasting evolutionary dynamics. Families II-3 and II-5 showed higher abundance and copy conservation in small ruminants. Family II-5 was closely related to circulating exogenous retroviruses and was identified with 22 copies sharing identical LTRs and 12 with complete coding capacities in the domestic goat. ConclusionsOur results indicate that two ERV families may have retain their transpositional activity within ruminants, particularly in domestic goats, illustrating distinct evolutionary dynamics among ruminant species. This work highlights the ongoing influence of ERVs on genomic landscapes and provides further insights into their evolutionary trajectories in ruminant genomes.

evolutionary biology↗

bioRxiv2024

Label-free Assessment of Complement-Dependent Cytotoxicity of Therapeutic Antibodies via a Whole-Cell MALDI Mass Spectrometry Bioassay

Potency assessment of monoclonal antibodies or corresponding biosimilars in cell-based assays is an essential prerequisite in biopharmaceutical research and development. However, cellular bioassays are still subject to limitations in sample throughput, speed, and often need costly reagents or labels as they are based on an indirect readout by luminescence or fluorescence. In contrast, whole-cell Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry (MS) has emerged as a direct, fast and label-free technology for functional drug screening being able to unravel the molecular complexity of cellular response to pharmaceutical reagents. However, this approach has not yet been used for cellular testing of biologicals. In this study, we have conceived, developed and bench-marked a label-free MALDI-MS based cell bioassay workflow for the functional assessment of complement-dependent cytotoxicity (CDC) of Rituximab antibody. By computational evaluation of response profiles followed by subsequent m/z feature annotation via fragmentation analysis and trapped ion mobility MS, we identified adenosine triphosphate and glutathione as readily MS-assessable metabolite markers for CDC and demonstrate that robust concentration-response characteristics can be obtained by MALDI-TOF MS. Statistical assay performance indicators suggest that whole-cell MALDI-TOF MS could complement the toolbox for functional cellular testing of biopharmaceuticals.

biochemistry↗