Biology subjects

Molitor, C.

Publications and source records attributed to Molitor, C..

5 recordsLinked to original sources

bioRxiv2025

Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials

In the HIV antibody mediated prevention (AMP) trials, the broadly neutralizing antibody VRC01 demonstrated protective efficacy against new diagnoses with susceptible HIV strains. To understand how VRC01 shaped breakthrough infections, we performed deep sequencing on 172 participants in the placebo and treatment arms, generating 63,444 gag-{Delta}pol (2.5 kb) and 53,088 rev-env-{Delta}nef (3 kb) sequences. Sequences were classified into transmitted founder lineages (TFLs), and infections with multiple distinct lineages were determined. Multilineage infections were detected in [~]38% of participants in both the African (HVTN 703/HPTN 081) and Americas/Europe (HVTN 704/HPTN 085) cohorts, regardless of placebo or treatment group, or cohort. The high levels of multilineage infections could be attributed to minor lineages (<5% abundance) identified in 20% of participants. Infection with VRC01 discordant viruses (IC80s >3-fold different) was observed in 40% of multilineage infections, with a trend toward greater intra-host neutralization differences with increasing VRC01 dose (Jonckheere-Terpstra test, p=0.072). In six VRC01 treated participants who acquired both sensitive (IC80<1{micro}g/ml) and resistant viruses (IC80>3{micro}g/ml), the sensitive lineages declined over time. Recombination was pervasive, observed in 63% of multilineage infections at the time of HIV diagnosis. In one treated participant infected with VRC01 discordant lineages, recombinant viruses preferentially inherited the resistance mutation (binomial p=0.004). In conclusion, our in-depth analysis of breakthrough viruses in the AMP trials revealed a high frequency of multilineage infections, including infections with viruses with different VRC01 sensitivities. This analysis also highlights the role of recombination in shaping intra-host viral evolution and facilitating escape from VRC01. SignificanceThis work advances our understanding of the diversity of initial viral infection and evolution and in vivo activity of broadly neutralizing antibodies (bNAbs). Deep sequencing revealed [~]38% of HIV acquisitions with multiple transmitted founder lineages, higher than previous studies. These occurrences were similar in the placebo and VRC01 groups. Viral recombination among post-acquisition variants was common under antibody selection and appeared to favor resistant sequences in the treatment group. These data suggest as with single antiviral therapy, passive and active immunization of bNAbs should be directed at multiple antigen targets of HIV-1.

molecular biology↗

bioRxiv2025

KILDA: identifying KIV-2 repeats from kmers

MotivationHigh concentration of lipoprotein(a), a lipoprotein with proatherogenic properties, is an important risk factor for cardiovascular disease. This concentration is mostly genetically determined by a complex interplay between the number of Kringle-IV type 2 repeats and Lipoprotein(a)-affecting variants. Besides lipoprotein(a) plasma concentration, there is an unmet need to identify individuals most at risk based on their LPA genotype. ResultsWe developed KILDA, a Nextflow pipeline, to identify the number of Kringle-IV type 2 repeats and Lp(a)-affecting variants directly from kmers generated from FASTQ files. The pipeline was tested on the 1000 Genomes Project (n=2459) and results were equivalent to DRAGEN-LPA (R2=0.93). In-silico datasets proved the robustness of KILDAs predictions under different scenarios of sequencing coverage and quality. ConclusionKILDA is an open-source and free-to-use pipeline to identify the number of Kringle-IV type 2 repeats and lipoprotein(a)-associated variants. Its results are equivalent to DRAGEN-LPA, offering a free and robust tool for determining the LPA kringle number even when inputting low coverage libraries. AvailabilityKILDA is publicly available at https://github.com/HCL-HUBL/KILDA along with a recipe to build an Apptainer image containing all the required dependencies. Contact: corentin.molitor@chu-lyon.fr Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2023

A chromosome-level genome assembly of Solanum chilense, a tomato wild relative associated with resistance to salinity and drought

Solanum chilense is a wild relative of tomato reported to exhibit resistance to biotic and abiotic stresses. There is potential to improve tomato cultivars via breeding with wild relatives, a process greatly accelerated by suitable genomic and genetic resources. In this study we generated a high-quality, chromosome-level, de novo assembly for the S. chilense accession LA1972 using a hybrid assembly strategy with [~]180 Gbp of Illumina short reads and [~]50 Gbp long PacBio reads. Further scaffolding was performed using Bionano optical maps and 10x Chromium(R) reads. The resulting sequences were arranged into 12 pseudomolecules using Hi-C sequencing. This resulted in a 901 Mbp assembly, with a completeness of 95%, as determined by Benchmarking with Universal Single-Copy Orthologs (BUSCO). Sequencing of RNA from multiple tissues resulting in [~]219 Gbp of reads was used to annotate the genome assembly with an RNA-Seq guided gene prediction, and for a de novo transcriptome assembly. This chromosome-level, high-quality reference genome for S. chilense accession LA1972 will support future breeding efforts for more sustainable tomato production. Gene sequences related to drought and salt resistance were compared between S. chilense and S. lycopersicum to identify amino acid variations with high potential for functional impact. These variants were subsequently analysed in 84 resequenced tomato lines across 12 different related species to explore the variant distributions. We identified a set of 7 putative impactful amino acid variants some of which may also impact on fruit development for example the ethylene-responsive transcription factor WIN1 and ethylene-insensitive protein 2. These variants could be tested for their ability to confer functional phenotypes to cultivars that have lost these variants.

bioinformatics↗

bioRxiv2021

De novo genome assembly and functional annotation for Fusarium langsethiae

MotivationFusarium langsethiae is a T-2 and HT-2 mycotoxins producing Fusarium species firstly characterised in 2004. It is commonly isolated from oats in Northern Europe. T-2 and HT-2 mycotoxins exhibit immunological and haemotological effects in animal health mainly through inhibition of protein, RNA and DNA synthesis. The development of a high-quality and comprehensively annotated assembly for this species is therefore essential in providing the molecular understanding and the mechanism of T-2 and HT-2 biosynthesis in F. langsethiae to help develop effective control strategies. ResultsThe F. langsethiae assembly was produced using PacBio long reads, which were then assembled independently using Canu, SMARTdenovo and Flye; producing a genome assembly total length of 59Mb and N50 of 3.51Mb. A total of 19,336 coding genes were identified using RNA-Seq informed ab-initio gene prediction. Finally, predicting genes were annotated using the basic local alignment search tool (BLAST) against the NCBI non-redundant (NR) genome database and protein hits were annotated using InterProScan. Genes with blast hits were functionally annotated with Gene Ontology. Contactf.mohareb@cranfield.ac.uk Data availabilityRaw sequence reads and assembled genome can be downloaded from: GenBank under the accession JAFFKB000000000

genomics↗

bioRxiv2020

De novo genome assembly and transcriptome analysis for the drought and salt resistant Solanum sitiens

Solanum sitiens is a self-incompatible wild relative of tomato, characterised by salt and drought resistance traits, with the potential to contribute to crop improvement in cultivated tomato. This species has a distinct morphology, classification and ecotype compared to other stress resistant wild tomato relatives such as S. pennellii and S. chilense. Therefore, the availability of a high-quality reference genome for S. sitiens will facilitate the genetic and molecular understanding of salt and drought resistance. Here, we present a de novo genome and transcriptome assembly for S. sitiens (Accession LA1974). A hybrid assembly strategy was followed using Illumina short reads ([~]159X coverage) and PacBio long reads ([~]44X coverage), generating a total of [~]262 Gbp of DNA sequence; in addition, [~]2,670 Gbp of BioNano data was obtained. A reference genome of 1,245 Mbp, arranged in 1,481 scaffolds with a N50 of 1,826 Mbp was generated. Genome completeness was estimated at 95% using the Benchmarking Universal Single-Copy Orthologs (BUSCO) and the K-mer Analysis Tool (KAT); this is within the range of current high-quality reference genomes for other tomato wild relatives. Additionally, we identified three large inversions compared to S. lycopersicum, containing several drought resistance related genes, such as beta-amylase 1 and YUCCA7. In addition, [~]63 Gbp of RNA-Seq were generated to support the prediction of 31,164 genes from the assembly, and perform a de novo transcriptome. Some of the protein clusters unique to S. sitiens were associated with genes involved in drought and salt resistance, including GLO1 and FQR1. This first reference genome for S. sitiens will provide a valuable resource to progress QTL studies to the gene level, and will assist molecular breeding to improve crop production in water-limited environments.

bioinformatics↗