Syndromic male subfertility: A network view of genome-phenome associations.

BACKGROUND: Male infertility is a disorder of the reproductive system with a highly complex genetic landscape. In most cases, the reason for male infertility remains unknown; however, the importance of genetic abnormalities in the diagnosis of subfertility/infertility is becoming increasingly recognized. Several syndromes include impaired male fertility in the clinical picture, although a comprehensive analysis of genetic causes of the syndromology perspective of male reproduction is not yet available. OBJECTIVES: (1) To develop a catalog of syndromes and corresponding genes associated with impaired male fertility and (2) to visualize an up-to-date genome-phenome network of syndromic male subfertility. MATERIALS AND METHODS: Published literature was retrieved from the Online Mendelian Inheritance in Man, Orphanet, Human Phenotype Ontology and PubMed databases using keywords "male infertility," "syndrome," "gene," and "case report"; time period from 1980 to September, 2021. Retrieved data were organized as a catalog and complemented with identification numbers of syndromes (MIM ID) and genes (Gene ID). The genome-phenome network and the phenome network were visualized using Cytoscape and Gephi software platforms. Protein-protein interaction analysis was performed using STRING tool. RESULTS: Retrieved syndromes were presented as (1) a catalog containing 63 syndromes and 93 associated genes, (2) a genome-phenome network including CHD7 and WT1 genes and Noonan and Kartagener syndromes, and (3) a phenome network including 63 syndromes, and 25 categories of clinical features. DISCUSSION: The developed catalog will contribute to the advances and translational impact toward understanding the factors of syndromic male infertility. Visualized networks provide simple, flexible tools for clinicians and researchers to quickly generate hypotheses and gain a deeper understanding of underlying mechanisms affecting male reproduction. CONCLUSION: Recognition of the significance of genome-phenome visualization as part of network medicine can help expedite efforts toward unravelling molecular mechanisms and enable advances personal/precision medicine of male reproduction and other complex traits.

Top Trends in Multiomics Research: Evaluation of 52 Published Studies and New Ways of Thinking Terminology and Visual Displays.

Multiomics study designs have significantly increased understanding of complex biological systems. The multiomics literature is rapidly expanding and so is their heterogeneity. However, the intricacy and fragmentation of omics data are impeding further research. To examine current trends in multiomics field, we reviewed 52 articles from PubMed and Web of Science, which used an integrated omics approach, published between March 2006 and January 2021. From studies, data regarding investigated loci, species, omics type, and phenotype were extracted, curated, and streamlined according to standardized terminology, and summarized in a previously developed graphical summary. Evaluated studies included 21 omics types or applications of omics technology such as genomics, transcriptomics, metabolomics, epigenomics, environmental omics, and pharmacogenomics, species of various phyla including human, mouse, Arabidopsis thaliana, Saccharomyces cerevisiae, and various phenotypes, including cancer and COVID-19. In the analyzed studies, diverse methods, protocols, results, and terminology were used and accordingly, assessment of the studies was challenging. Adoption of standardized multiomics data presentation in the future will further buttress standardization of terminology and reporting of results in systems science. This shall catalyze, we suggest, innovation in both science communication and laboratory medicine by making available scientific knowledge that is easier to grasp, share, and harness toward medical breakthroughs.

Molecular Mechanisms of Syndromic Cryptorchidism: Data Synthesis of 50 Studies and Visualization of Gene-Disease Network.

Background: Cryptorchidism is one of the most frequent congenital birth defects in male children and is present in 2-4% of full-term male births. It has several possible health effects including reduced fertility, increased risk for testicular neoplasia, testicular torsion, and psychological consequences. Cryptorchidism is often diagnosed as comorbid; copresent with other diseases. It is also present in clinical picture of several syndromes. However, this field has not been systematically studied. The aim of the present study was to catalog published cases of syndromes which include cryptorchidism in the clinical picture and associated genomic information. Methods: The literature was extracted from Public/Publisher MEDLINE and Web of Science databases, using the keywords including: syndrome, cryptorchidism, undescended testes, loci, and gene. The obtained data was organized in a table according to the previously proposed standardized data format. The results of the study were visually represented using Gephi and karyotype view. Results: Fifty publications had sufficient data for analysis. Literature analysis resulted in 60 genomic loci, associated with 44 syndromes that have cryptorchidism in clinical picture. Genomic loci included 38 protein-coding genes and 22 structural variations containing microdeletions and microduplications. Loci, associated with syndromic cryptorchidism are located on 16 chromosomes. Visualization of retrieved data is presented in a gene-disease network. Conclusions: The study is ongoing and further studies will be needed to develop a complete catalog with the data from upcoming publications. Additional studies will also be needed for revealing of molecular mechanisms associated with syndromic cryptorchidism and revealing complete diseasome network.