TWAS Atlas: a curated knowledgebase of transcriptome-wide association studies.

Transcriptome-wide association studies (TWASs), as a practical and prevalent approach for detecting the associations between genetically regulated genes and traits, are now leading to a better understanding of the complex mechanisms of genetic variants in regulating various diseases and traits. Despite the ever-increasing TWAS outputs, there is still a lack of databases curating massive public TWAS information and knowledge. To fill this gap, here we present TWAS Atlas (https://ngdc.cncb.ac.cn/twas/), an integrated knowledgebase of TWAS findings manually curated from extensive literature. In the current implementation, TWAS Atlas collects 401,266 high-quality human gene-trait associations from 200 publications, covering 22,247 genes and 257 traits across 135 tissue types. In particular, an interactive knowledge graph of the collected gene-trait associations is constructed together with single nucleotide polymorphism (SNP)-gene associations to build up comprehensive regulatory networks at multi-omics levels. In addition, TWAS Atlas, as a user-friendly web interface, efficiently enables users to browse, search and download all association information, relevant research metadata and annotation information of interest. Taken together, TWAS Atlas is of great value for promoting the utility and availability of TWAS results in explaining the complex genetic basis as well as providing new insights for human health and disease research.

TSomVar: a tumor-only somatic and germline variant identification method with random forest.

Somatic variants act as critical players during cancer occurrence and development. Thus, an accurate and robust method to identify them is the foundation of cutting-edge cancer genome research. However, due to low accessibility and high individual-/sample-specificity of the somatic variants in tumor samples, the detection is, to date, still crammed with challenges, particularly when lacking paired normal samples as control. To solve this burning issue, we developed a tumor-only somatic and germline variant identification method (TSomVar) using the random forest algorithm established on sample-specific variant datasets derived from genotype imputation, reads-mapping level annotation and functional annotation. We trained TSomVar by using genomic variant datasets of three major cancer types: colorectal cancer, hepatocellular carcinoma and skin cutaneous melanoma. Compared with existing tumor-only somatic variant identification tools, TSomVar shows excellent performances in somatic variant detection with higher accuracy and better capability of recalling for test datasets from colorectal cancer and skin cutaneous melanoma. In addition, TSomVar is equipped with the competence of accurately identifying germline variants in tumor samples. Taken together, TSomVar will undoubtedly facilitate and revolutionize somatic variant explorations in cancer research.

NucMap: a database of genome-wide nucleosome positioning map across species.

Dynamics of nucleosome positioning affects chromatin state, transcription and all other biological processes occurring on genomic DNA. While MNase-Seq has been used to depict nucleosome positioning map in eukaryote in the past years, nucleosome positioning data is increasing dramatically. To facilitate the usage of published data across studies, we developed a database named nucleosome positioning map (NucMap, http://bigd.big.ac.cn/nucmap). NucMap includes 798 experimental data from 477 samples across 15 species. With a series of functional modules, users can search profile of nucleosome positioning at the promoter region of each gene across all samples and make enrichment analysis on nucleosome positioning data in all genomic regions. Nucleosome browser was built to visualize the profiles of nucleosome positioning. Users can also visualize multiple sources of omics data with the nucleosome browser and make side-by-side comparisons. All processed data in the database are freely available. NucMap is the first comprehensive nucleosome positioning platform and it will serve as an important resource to facilitate the understanding of chromatin regulation.

A comprehensive evaluation of the potential of three next-generation short-read-based plant pan-genome construction strategies for the identification of novel non-reference sequence.

Pan-genome studies are important for understanding plant evolution and guiding the breeding of crops by containing all genomic diversity of a certain species. Three short-read-based strategies for plant pan-genome construction include iterative individual, iteration pooling, and map-to-pan. Their performance is very different under various conditions, while comprehensive evaluations have yet to be conducted nowadays. Here, we evaluate the performance of these three pan-genome construction strategies for plants under different sequencing depths and sample sizes. Also, we indicate the influence of length and repeat content percentage of novel sequences on three pan-genome construction strategies. Besides, we compare the computational resource consumption among the three strategies. Our findings indicate that map-to-pan has the greatest recall but the lowest precision. In contrast, both two iterative strategies have superior precision but lower recall. Factors of sample numbers, novel sequence length, and the percentage of novel sequences' repeat content adversely affect the performance of all three strategies. Increased sequencing depth improves map-to-pan's performance, while not affecting the other two iterative strategies. For computational resource consumption, map-to-pan demands considerably more than the other two iterative strategies. Overall, the iterative strategy, especially the iterative pooling strategy, is optimal when the sequencing depth is less than 20X. Map-to-pan is preferable when the sequencing depth exceeds 20X despite its higher computational resource consumption.