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Copy Number Variation (CNV) refers to a type of structural genomic alteration in which a segment of chromosome is duplicated or deleted. To date, many CNVs have been identified as causative genetic elements for several diseases and phenotypes. However, performing a CNV-based genome-wide association study is challenging due to inconsistency in length and occurrence of CNVs across different individuals under investigation. One of the most efficient strategies to address this issue is building CNV regions (genomic regions in which CNVs are overlapping - CNVRs). However, this approach is susceptible to a high false positive rate due to overlapping and co-occurring of confounding CNVRs with true positive CNVRs. Here, we develop PeakCNV that differentiates false-positive CNVRs from true positives by calculating a new metric, independence ranking score, (IR-score) via a feature ranking approach. We compared the performance of PeakCNV with other current existing tools by carrying out two case studies one using the CNV genotype data for individuals with prostate cancer (194 cases and 2,392 healthy individuals) and the second one for individuals with neurodevelopmental disorders (19,642 cases and 6,451 healthy individuals). Crucially, our benchmarking analyses on prostate cancer cohort indicated that PeakCNV identifies a fewer risk candidate CNVRs with shorter lengths compared to other tools. Importantly, these CNVRs cover a greater proportion of case over healthy individuals compared to other tools. The accuracy of PeakCNV in identifying relevant candidate CNVRs was reproducible in the case study on neurodevelopmental disorders. Using data from the FANTOM5 expression atlas and the Clinical Genomic Database, we show that the candidate CNVRs identified by PeakCNV for neurodevelopmental disorders overlap with a greater number of genes with the brain-enriched expression, and a greater number of genes that are associated with neurological conditions compared to candidate CNVRs identified by other tools. Taken together, PeakCNV outperformed current existing CNV association study tools by identifying more biologically meaningful CNVRs relevant to the phenotype of interest. PeakCNV is publicly available for the analysis of CNV-associated diseases and is accessible from https://rdrr.io/github/mahdieh1/PeakCNV.

Prostate cancer (PC) is the most frequently diagnosed non-skin cancer in the world. Previous studies have shown that genomic alterations represent the most common mechanism for molecular alterations responsible for the development and progression of PC. This highlights the importance of identifying functional genomic variants for early detection in high-risk PC individuals. Great efforts have been made to identify common protein-coding genetic variations; however, the impact of non-coding variations, including regulatory genetic variants, is not well understood. Identification of these variants and the underlying target genes will be a key step in improving the detection and treatment of PC. To gain an understanding of the functional impact of genetic variants, and in particular, regulatory variants in PC, we developed an integrative pipeline (AGV) that uses whole genome/exome sequences, GWAS SNPs, chromosome conformation capture data, and ChIP-Seq signals to investigate the potential impact of genomic variants on the underlying target genes in PC. We identified 646 putative regulatory variants, of which 30 significantly altered the expression of at least one protein-coding gene. Our analysis of chromatin interactions data (Hi-C) revealed that the 30 putative regulatory variants could affect 131 coding and non-coding genes. Interestingly, our study identified the 131 protein-coding genes that are involved in disease-related pathways, including Reactome and MSigDB, for most of which targeted treatment options are currently available. Notably, our analysis revealed several non-coding RNAs, including RP11-136K7.2 and RAMP2-AS1, as potential enhancer elements of the protein-coding genes CDH12 and EZH1, respectively. Our results provide a comprehensive map of genomic variants in PC and reveal their potential contribution to prostate cancer progression and development.

Here we developed KARAJ, a fast and flexible Linux command-line tool to automate the end-to-end process of querying and downloading a wide range of genomic and transcriptomic sequence data types. The input to KARAJ is a list of PMCIDs or publication URLs or various types of accession numbers to automate four tasks as follows; firstly, it provides a summary list of accessible datasets generated by or used in these scientific articles, enabling users to select appropriate datasets; secondly, KARAJ calculates the size of files that users want to download and confirms the availability of adequate space on the local disk; thirdly, it generates a metadata table containing sample information and the experimental design of the corresponding study; and lastly, it enables users to download supplementary data tables attached to publications. Further, KARAJ provides a parallel downloading framework powered by Aspera connect which reduces the downloading time significantly.