scalepopgen: Bioinformatic Workflow Resources Implemented in Nextflow for Comprehensive Population Genomic Analyses.

Population genomic analyses such as inference of population structure and identifying signatures of selection usually involve the application of a plethora of tools. The installation of tools and their dependencies, data transformation, or series of data preprocessing in a particular order sometimes makes the analyses challenging. While the usage of container-based technologies has significantly resolved the problems associated with the installation of tools and their dependencies, population genomic analyses requiring multistep pipelines or complex data transformation can greatly be facilitated by the application of workflow management systems such as Nextflow and Snakemake. Here, we present scalepopgen, a collection of fully automated workflows that can carry out widely used population genomic analyses on the biallelic single nucleotide polymorphism data stored in either variant calling format files or the plink-generated binary files. scalepopgen is developed in Nextflow and can be run locally or on high-performance computing systems using either Conda, Singularity, or Docker. The automated workflow includes procedures such as (i) filtering of individuals and genotypes; (ii) principal component analysis, admixture with identifying optimal K-values; (iii) running TreeMix analysis with or without bootstrapping and migration edges, followed by identification of an optimal number of migration edges; (iv) implementing single-population and pair-wise population comparison-based procedures to identify genomic signatures of selection. The pipeline uses various open-source tools; additionally, several Python and R scripts are also provided to collect and visualize the results. The tool is freely available at https://github.com/Popgen48/scalepopgen.

Whole-genome SNP genotyping unveils ancestral and recent introgression in wild and domestic goats.

After the domestication of goats around 10,000 years before the present (BP), humans transported goats far beyond the range of their wild ancestor, the bezoar goat. This brought domestic goats into contact with many wild goat species such as ibex and markhor, enabling introgression between domestic and wild goats. To investigate this, while shedding light on the taxonomic status of wild and domestic goats, we analysed genome-wide SNP data of 613 specimens from 14 taxonomic units, including Capra hircus, C. pyrenaica, C. ibex (from Switzerland, Austria, Germany and Slovenia), C. aegagrus aegagrus, C. a. cretica, C. h. dorcas, C. caucasica caucasica, C. c. severtzovi, C. c. cylindricornis, C. falconeri, C. sibirica sibirica, C. s. alaiana and C. nubiana, as well as Oreamnos americanus (mountain goat) as an outgroup. To trace gene flow between domestic and wild goats, we integrated genotype data of local goat breeds from the Alps as well as from countries such as Spain, Greece, Türkiye, Egypt, Sudan, Iran, Russia (Caucasus and Altai) and Pakistan. Our phylogenetic analyses displayed a clear separation between bezoar-type and ibex-type clades with wild goats from the Greek islands of Crete and Youra clustered within domestic goats, confirming their feral origin. Our analyses also revealed gene flow between the lineages of Caucasian tur and domestic goats that most likely occurred before or during early domestication. Within the clade of domestic goats, analyses inferred gene flow between African and Iberian goats. The detected events of introgression were consistent with previous reports and offered interesting insights into the historical relationships among domestic and wild goats.

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.

Post-genotyping optimization of dataset formation could affect genetic diversity parameters: an example of analyses with alpine goat breeds.

BACKGROUND: Local breeds retained unique genetic variability important for adaptive potential especially in light of challenges related to climate change. Our first objective was to perform, for the first time, a genome-wide diversity characterization using Illumina GoatSNP50 BeadChip of autochthonous Dreznica goat breed from Slovenia, and five and one local breeds from neighboring Austria and Italy, respectively. For optimal conservation and breeding programs of endangered local breeds, it is important to detect past admixture events and strive for preservation of purebred representatives of each breed with low or without admixture. In the second objective, we hence investigated the effect of inclusion or exclusion of outliers from datasets on genetic diversity and population structure parameters. RESULTS: Distinct genetic origin of the Dreznica goat was demonstrated as having closest nodes to Austrian and Italian breeds. A phylogenetic study of these breeds with other goat breeds having SNP data available in the DRYAD repository positioned them in the alpine, European and global context. Swiss breeds clustered with cosmopolitan alpine breeds and were closer to French and Spanish breeds. On the other hand, the Dreznica goat, Austrian and Italian breeds were closer to Turkish breeds. Datasets where outliers were excluded affected estimates of genetic diversity parameters within the breed and increased the pairwise genetic distances between most of the breeds. Alpine breeds, including Dreznica, Austrian and Italian goats analyzed here, still exhibit relatively high levels of genetic variability, homogeneous genetic structure and strong geographical partitioning. CONCLUSIONS: Genetic diversity analyses revealed that the Slovenian Dreznica goat has a distinct genetic identity and is closely related to the neighboring Austrian and Italian alpine breeds. These results expand our knowledge on phylogeny of goat breeds from easternmost part of the European Alps. The here employed outlier test and datasets optimization approaches provided an objective and statistically powerful tool for removal of admixed outliers. Importance of this test in selecting the representatives of each breed is warranted to obtain more objective diversity parameters and phylogenetic analysis. Such parameters are often the basis of breeding and management programs and are therefore important for preserving genetic variability and uniqueness of local rare breeds.