Next-generation diagnostics and disease-gene discovery with the Exomiser

By D. Smedley, Julius O. B. Jacobsen, M. Jäger, Sebastian Köhler, M. Holtgrewe, Max Schubach, Enrico Siragusa, T. Żemojtel, Orion J. Buske, Nicole L. Washington and 3 more. Nature Protocols, 2015

400 citations recorded by the source corpus.

Exomiser is an application that prioritizes genes and variants in next-generation sequencing (NGS) projects for novel disease-gene discovery or differential diagnostics of Mendelian disease. Exomiser comprises a suite of algorithms for prioritizing exome sequences using random-walk analysis of protein interaction networks, clinical relevance and cross-species phenotype comparisons, as well as a wide range of other computational filters for variant frequency, predicted pathogenicity and pedigree analysis. In this protocol, we provide a detailed explanation of how to install Exomiser and use it to prioritize exome sequences in a number of scenarios. Exomiser requires ∼3 GB of RAM and roughly 15–90 s of computing time on a standard desktop computer to analyze a variant call format (VCF) file. Exomiser is freely available for academic use from http://www.sanger.ac.uk/science/tools/exomiser.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c2e7a98e0fd838050506101d31a12b8717ab8c23

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Citations in the corpus

The Human Phenotype Ontology in 2021 (2020, background): “For example, Exomiser (15) leverages the semantic associations between HPO, MP and ZP to prioritize variants effectively by matching human phenotypic abnormalities with phenotypes observed in animal models with knockouts of genes orthologous to human disease-associated genes.”
Settling the score: variant prioritization and Mendelian disease (2017, methodology): “These tools vary from ontology-based semantic similarity methods to more complex machine-learning techniques 75–80 .”
A Whole-Genome Analysis Framework for Effective Identification of Pathogenic Regulatory Variants in Mendelian Disease. (2016, methodology): “55,56 To allow Genomiser to run in a reasonable time frame (~4–10 min) and with a minimal memory (~4–10 GB), we had to reimplement Exomiser to be able to stream variants from a VCF ﬁle and run the various ﬁltering and prioritization steps in a user-conﬁgured manner rather than the predeﬁned…”