SpermatogenesisOnline 1.0: a resource for spermatogenesis based on manual literature curation and genome-wide data mining

Abstract

Human infertility affects 10–15% of couples, half of which is attributed to the male partner. Abnormal spermatogenesis is a major cause of male infertility. Characterizing the genes involved in spermatogenesis is fundamental to understand the mechanisms underlying this biological process and in developing treatments for male infertility. Although many genes have been implicated in spermatogenesis, no dedicated bioinformatic resource for spermatogenesis is available. We have developed such a database, SpermatogenesisOnline 1.0 (http://mcg.ustc.edu.cn/sdap1/spermgenes/), using manual curation from 30 233 articles published before 1 May 2012. It provides detailed information for 1666 genes reported to participate in spermatogenesis in 37 organisms. Based on the analysis of these genes, we developed an algorithm, Greed AUC Stepwise (GAS) model, which predicted 762 genes to participate in spermatogenesis (GAS probability >0.5) based on genome-wide transcriptional data in Mus musculus testis from the ArrayExpress database. These predicted and experimentally verified genes were annotated, with several identical spermatogenesis-related GO terms being enriched for both classes. Furthermore, protein–protein interaction analysis indicates direct interactions of predicted genes with the experimentally verified ones, which supports the reliability of GAS. The strategy (manual curation and data mining) used to develop SpermatogenesisOnline 1.0 can be easily extended to other biological processes.

Systematic Analysis of the Phosphoproteome and Kinase-substrate Networks in the Mouse Testis

“…S7), and it is interesting that 83 of the 117 (ϳ71%) phosphorylated substrates were enriched in both IMAC and TiO 2 . Although PLKs were not annotated as spermatogenesis-related in the gene ontology database (40) or SpermatogenesisOnline database (43), a number of spermatogenesis-related proteins were predicted to be regulated by PLKs in our study. The PLK-regulated spermatogenesis-related sub-KSPN is presented in Fig.…”

In‐depth proteomic analysis of whole testis tissue from the adult rhesus macaque

“…Detailed analysis further showed that eight genes are essential for spermatogonia proliferation, 78 genes are essential for meiosis, and 141 genes are essential for spermatogenesis (Supporting Information Data 6). We further downloaded human spermatogenesis‐associated genes from SpermatogenesisOnline 1.0 and obtained a list of 322 human Ensembl genes . A total of 134 macaque testis genes have one‐to‐one orthologs with human spermatogenesis‐associated genes (Supporting Information Data 2).…”

A DNAH17 missense variant causes flagella destabilization and asthenozoospermia

“…S1 B). GPS1, HID1, and USP36 are annotated ubiquitously expressed in various tissues (Zhang et al, 2013; DNAH17 mRNA exhibits testis-specific expression [Milisav and Affara, 1998]). Given that our patients did not show any other symptoms except asthenozoospermia, the homozygous missense variant (c.G5408A) in DNAH17 was favorably presumed to be responsible for the diminished sperm motility in the patients.…”

“…(2) variants with minor allele frequencies >0.05, suggested by American College of Medical Genetics and Genomics for benign mutations (Richards et al, 2015), in any of the public databases, 1000 Genome project (Auton et al, 2015), ESP6500 (Fu et al, 2013), or ExAC database (Lek et al, 2016), and variants homozygous in our in-house WES variants call set generated from 578 fertile male samples (41 Pakistanis, 254 Chinese, and 283 Europeans) were excluded; (3) variants potentially affecting protein sequence and (4) in genes expressed in testis based on Sperma-togenesisOnline1.0 (https://mcg.ustc.edu.cn/bsc/spermgenes/; Zhang et al, 2013) were kept; (5) variants predicted to be deleterious by less than half of the 13 software (Adzhubei et al, 2010;Choi et al, 2012;Chun and Fay, 2009;Davydov et al, 2010;Dong et al, 2015;Lindblad-Toh et al, 2011;Reva et al, 2011;Schwarz et al, 2014;Shihab et al, 2013;Shihab et al, 2015;Sim et al, 2012) covering them were excluded; (6) variants in genes for which inactivation has no effects on male fertility or spermatogenesis based on Spermatogenesi-sOnline1.0 (Zhang et al, 2013) were excluded; (7) the remaining variants were subsequently detected by Sanger sequencing in all the family members available (III:1, III:2, and IV:1-7). Fig.…”