An atlas of evidence-based phenotypic associations across the mouse phenome

Abstract

An atlas of evidence-based phenotypic associations across the mouse phenome nobuhiko tanaka * & Hiroshi Masuya to date, reliable relationships between mammalian phenotypes, based on diagnostic test measurements, have not been reported on a large scale. the purpose of this study was to present a large mouse phenotype-phenotype relationships dataset as a reference resource, alongside detailed evaluation of the resource. We used bias-minimized comprehensive mouse phenotype data and applied association rule mining to a dataset consisting of only binary (normal and abnormal phenotypes) data to determine relationships among phenotypes. We present 3,686 evidence-based significant associations, comprising 345 phenotypes covering 60 biological systems (functions), and evaluate their characteristics in detail. To evaluate the relationships, we defined a set of phenotype-phenotype association pairs (PPAPs) as a module of phenotypic expression for each of the 345 phenotypes. By analyzing each PPAP, we identified phenotype sub-networks consisting of the largest numbers of phenotypes and distinct biological systems. furthermore, using hierarchical clustering based on phenotype similarities among the 345 PPAPs, we identified seven community types within a putative phenome-wide association network. Moreover, to promote leverage of these data, we developed and published web-application tools. these mouse phenome-wide phenotype-phenotype association data reveal general principles of relationships among mammalian phenotypes and provide a reference resource for biomedical analyses.

Establishment and application of information resource of mutant mice in RIKEN BioResource Research Center

“…To provide reliable, weighted phenotype-phenotype relationships as a reference data resource useful to detailed evaluation of the mouse mutant resources, RIKEN BRC worked out an association rule mining of a dataset consisting of only binary (normal and abnormal phenotypes) data to determine relationships among phenotypes with IMPC data which is a bias-minimized comprehensive data of mouse phenotypes. As a result, a set of phenotypephenotype association pairs (PPAPs) as a module of phenotypic expression for each of the 345 phenotypes were defined [36,37]. By analyzing each PPAP, phenotype sub-networks consisting of the phenotypes and distinct biological systems were also defined.…”

“…Provision of advanced mathematical methods to analyze big-data is one of the most effective ways to add value to bioresources discovery of novel biological functions or principles of life systems. In addition to [37] for details phenotype-phenotype associations, we also work in the development of a novel mathematical method termed "Energy landscape analysis" to visualize energy states or stabilities using omics data of microflora or transcriptome of environments or organisms [40]. This methodology is expected to be useful for controlling the biological state of soil, intestine, and cell differentiation which are composed of multiple factors with intricate interactions.…”

“…Lower panel shows data representation in the web application (https://brc-riken.shinyapps.io/phenotypic_associations_across_the_ mouse_phenome/) in which users can select, search and download any relationships. SeeTanaka et al (2020)…”

Asian Mouse Mutagenesis Resource Association (AMMRA): mouse genetics and laboratory animal resources in the Asia Pacific

“…RIKEN BRC has collected, preserved, quality-controlled and distributed valuable mouse resources created mainly in Japan with support of the global research community (Yoshiki et al 2009 ; Masuya et al 2021 ). Four divisions and three teams at RIKEN BRC have collaborated to participate in AMMRA and IMPC, facilitate dissemination of mouse resources, and enrich the value of the strains with broad-based phenotyping data and high-quality genome information (Takada et al 2015 ; Dickinson et al 2016 ; Bowl et al 2017 ; Karp et al 2017 ; Rozman et al 2018 ; Lloyd et al 2020 ; Tanaka and Masuya 2020 ) as well as sharing relevant knowledge and technologies with the global community (Masuya et al 2011 ; Kobayashi et al 2018 ). Moreover, RIKEN BRC provides the domestic research community with a comprehensive phenotype analysis platform referred to as the “Japan Mouse Clinic” (Wakana et al 2009 ; Kishimoto et al 2018 ; Furuse et al 2019 ; Matsumura et al 2020 ).…”