1. Candidate Explorer: a tool for discovery, evaluation, and display of mutations causing significant immune phenotypes
- Author
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Priscilla Anderton, Stephen Aplin Lyon, Zhao Zhang, Takuma Misawa, Meron Tadesse, Duanwu Zhang, Tao Yue, Miao Tang, Lindsay Scott, Jeffrey A. SoRelle, Hexin Shi, Jennifer Cardin, Sydney Cooper, Jiexia Quan, Jin Huk Choi, Nathan Stewart, Emre E. Turer, Chun Hui Bu, Sara Schneider, Xue Zhong, Dawson Medler, Katie Keller, Alexyss Johnson, Brandon Nguyen, Darui Xu, Braden Hayse, Bruce Beutler, Lei Sun, Jianhui Wang, Evan Nair-Gill, Edward Rodriguez, Aijie Liu, Sara Hildebrand, Qihua Sun, Andrew Wadley, Sara Mazal, Xiaohong Li, Gabrielle Coolbaugh, Ying Wang, Rochelle Simpson, Eva Marie Y. Moresco, John Santoyo, Baifang Qin, Roxana Farokhnia, Andrew Sakla, Amy Bronikowski, and Hannah Coco
- Subjects
Genetics ,Linkage (software) ,Mutation ,Immune system ,Software tool ,medicine ,Biology ,Quantitative trait locus ,medicine.disease_cause ,Gene ,Phenotype ,Selection (genetic algorithm) - Abstract
When applied to immunity, forward genetic studies use meiotic mapping to provide strong statistical evidence that a particular mutation is causative of a particular immune phenotype. Notwithstanding this, co-segregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the selection of authentic causative mutations using a machine learning software tool, Candidate Explorer (CE), which integrates 65 data features into a single numeric score, mathematically convertible to the likelihood of verification of any putative mutation-phenotype association. CE has identified most genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus. The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.
- Published
- 2020
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