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Marquet, C.

Publications and source records attributed to Marquet, C..

2 recordsLinked to original sources

LambdaPP: Fast and accessible protein-specific phenotype predictions

The availability of accurate and fast Artificial Intelligence (AI) solutions predicting aspects of proteins are revolutionizing experimental and computational molecular biology. The webserver LambdaPP aspires to supersede PredictProtein, the first internet server making AI protein predictions available in 1992. Given a protein sequence as input, LambdaPP provides easily accessible visualizations of protein 3D structure, along with predictions at the protein level (GeneOntology, subcellular location), and the residue level (binding to metal ions, small molecules, and nucleotides; conservation; intrinsic disorder; secondary structure; alpha-helical and beta-barrel transmembrane segments; signal-peptides; variant effect) in seconds. The structure prediction provided by LambdaPP - leveraging ColabFold and computed in minutes - is based on MMseqs2 multiple sequence alignments. All other feature prediction methods are based on the pLM ProtT5. Queried by a protein sequence, LambdaPP computes protein and residue predictions almost instantly for various phenotypes, including 3D structure and aspects of protein function. Accessibility StatementLambdaPP is freely available for everyone to use under embed.predictprotein.org, the interactive results for the case study can be found under https://embed.predictprotein.org/o/Q9NZC2. The frontend of LambdaPP can be found on GitHub (github.com/sacdallago/embed.predictprotein.org), and can be freely used and distributed under the academic free use license (AFL-2). For high-throughput applications, all methods can be executed locally via the bio-embeddings (bioembeddings.com) python package, or docker image at ghcr.io/bioembeddings/bio_embeddings, which also includes the backend of LambdaPP. Impact StatementWe introduce LambdaPP, a webserver integrating fast and accurate sequence-only protein feature predictions based on embeddings from protein Language Models (pLMs) available in seconds along with high-quality protein structure predictions. The intuitive interface invites experts and novices to benefit from the latest machine learning tools. LambdaPPs unique combination of predicted features may help in formulating hypotheses for experiments and as input to bioinformatics pipelines.

bioinformatics↗

De novo germline mutation in the Dual Specificity Phosphatase 10 gene accelerates autoimmune diabetes in Non-Obese Diabetic (NOD) mice

Here we report the isolation by selective breeding of two sublines of Non-Obese Diabetic (NOD) mice exhibiting a significant difference in the incidence of autoimmune type 1 diabetes (T1D). Whole genome sequencing of the NOD/NckH (high T1D incidence) and NOD/NckL (low T1D incidence) revealed the presence of a limited number of variants specific to each subline. Treating the age of T1D onset as a quantitative trait and using automated meiotic mapping (AMM), enhanced susceptibility in the NOD/NckH subline was unambiguously attributed to a recessive allele of Dusp10 which encodes a dual specificity phosphatase. The causative effect of the mutation was verified with a high level of confidence by targeting Dusp10 with CRISPR/Cas9 in NOD/NckL mice: in these animals a higher incidence of diabetes was observed. Expression of wild-type Dusp10 correlated with higher levels of surface PD-L1 in the islets of NOD/NckL mice.

immunology↗