MosaicBase: A Knowledgebase of Postzygotic Mosaic Variants in Noncancer Disease-related and Healthy Human Individuals

Xiaoxu Yang,Changhong Yang,Xianing Zheng,Luoxing Xiong,Yutian Tao,Meng Wang,Adam Yongxin Ye,Qixi Wu,Yanmei Dou,Junyu Luo,Liping Wei,August Yue Huang

doi:10.1016/j.gpb.2020.05.002

Abstract

Mosaic variants resulting from postzygotic mutations are prevalent in the human genome and play important roles in human diseases. However, except for cancer-related variants, there is no collection of postzygotic mosaic variants in noncancer disease-related and healthy individuals. Here, we present MosaicBase, a comprehensive database that includes 6698 mosaic variants related to 266 noncancer diseases and 27,991 mosaic variants identified in 422 healthy individuals. Genomic and phenotypic information of each variant was manually extracted and curated from 383 publications. MosaicBase supports the query of variants with Online Mendelian Inheritance in Man (OMIM) entries, genomic coordinates, gene symbols, or Entrez IDs. We also provide an integrated genome browser for users to easily access mosaic variants and their related annotations for any genomic region. By analyzing the variants collected in MosaicBase, we find that mosaic variants that directly contribute to disease phenotype show features distinct from those of variants in individuals with mild or no phenotypes, in terms of their genomic distribution, mutation signatures, and fraction of mutant cells. MosaicBase will not only assist clinicians in genetic counseling and diagnosis but also provide a useful resource to understand the genomic baseline of postzygotic mutations in the general human population. MosaicBase is publicly available at http://mosaicbase.com/ or http://49.4.21.8:8000.

Highlights

Genomic mosaicism results from postzygotic mutations arising during embryonic development, tissue self-renewal [1], aging processes [2], or exposure to other DNA-damaging circumstances [3]
383 journal research articles about mosaic SNVs and indels in noncancer individuals that were published between Jan 1989 and May 2018 were collected into MosaicBase
MosaicBase currently contains 34,689 mosaic SNVs and indels identified in patients with noncancer diseases and their parents, as well as asymptomatic individuals, with rich information at the publication, individual, gene and variant levels

Summary

Introduction

Genomic mosaicism results from postzygotic mutations arising during embryonic development, tissue self-renewal [1], aging processes [2], or exposure to other DNA-damaging circumstances [3]. For more than 1,000 search results, we scrutinized the main text as well as supplemental information to confirm the relevance of each publication After this process, 383 journal research articles about mosaic SNVs and indels in noncancer individuals that were published between Jan 1989 and May 2018 were collected into MosaicBase. MosaicBase included a “Statistics” page to show a summary of all the collected mosaic variants (Figure 2E) and a “Tutorials” page (Figure 2F) with detailed introductions about the database and its search modes, data presentation, and genome browser. MosaicBase currently includes 383 journal research articles, letters, and clinical genetic reports about noncancer postzygotic mosaic variants that were published from 1989 to 2018 (Figure 3A), with an accelerated accumulation of mosaic-related publications boosted by the recent advances in NGS technologies. These results highlighted the importance of the MAF information of mosaic variants in clinical applications such as genetic counseling

Discussion

Findings

Figures and Legends