The vast noncoding portion of the human genome harbors a rich array of functional elements and disease-causing regulatory variants. Recent high-throughput chromosome conformation capture studies have outlined the principles of these elements interacting and regulating the expression of distal target genes through three-dimensional (3D) chromatin looping. Here we present 3DSNP, an integrated database for annotating human noncoding variants by exploring their roles in the distal interactions between genes and regulatory elements. 3DSNP integrates 3D chromatin interactions, local chromatin signatures in different cell types and linkage disequilibrium (LD) information from the 1000 Genomes Project. 3DSNP provides informative visualization tools to display the integrated local and 3D chromatin signatures and the genetic associations among variants. Data from different functional categories are integrated in a scoring system that quantitatively measures the functionality of SNPs to help select important variants from a large pool. 3DSNP is a valuable resource for the annotation of human noncoding genome sequence and investigating the impact of noncoding variants on clinical phenotypes. The 3DSNP database is available at http://biotech.bmi.ac.cn/3dsnp/.

Hi-C is commonly used to study three-dimensional genome organization. However, due to the high sequencing cost and technical constraints, the resolution of most Hi-C datasets is coarse, resulting in a loss of information and biological interpretability. Here we develop DeepHiC, a generative adversarial network, to predict high-resolution Hi-C contact maps from low-coverage sequencing data. We demonstrated that DeepHiC is capable of reproducing high-resolution Hi-C data from as few as 1% downsampled reads. Empowered by adversarial training, our method can restore fine-grained details similar to those in high-resolution Hi-C matrices, boosting accuracy in chromatin loops identification and TADs detection, and outperforms the state-of-the-art methods in accuracy of prediction. Finally, application of DeepHiC to Hi-C data on mouse embryonic development can facilitate chromatin loop detection. We develop a web-based tool (DeepHiC, http://sysomics.com/deephic) that allows researchers to enhance their own Hi-C data with just a few clicks. We developed a novel method, DeepHiC, for enhancing Hi-C data resolution from low-coverage sequencing data using generative adversarial network. DeepHiC is capable of reproducing high-resolution (10-kb) Hi-C data with high quality even using 1/100 downsampled reads. Our method outperforms the previous methods in Hi-C data resolution enhancement, boosting accuracy in chromatin loops identification and TADs detection. Application of DeepHiC on mouse embryonic development data shows that enhancements afforded by DeepHiC facilitates the chromatin loops prediction of these data, yielding significant interactions more enriched in open chromatin regions and gene promoters. We also developed a user-friendly web server (http://sysomics.com/deephic) that allows researchers to enhance their own low-coverage Hi-C data with just few clicks.

Essential genes are those whose loss of function compromises organism viability or results in profound loss of fitness. Recent gene-editing technologies have provided new opportunities to characterize essential genes. Here, we present an integrated analysis that comprehensively and systematically elucidates the genetic and regulatory characteristics of human essential genes. First, we found that essential genes act as ‘hubs’ in protein–protein interaction networks, chromatin structure and epigenetic modification. Second, essential genes represent conserved biological processes across species, although gene essentiality changes differently among species. Third, essential genes are important for cell development due to their discriminate transcription activity in embryo development and oncogenesis. In addition, we developed an interactive web server, the Human Essential Genes Interactive Analysis Platform (http://sysomics.com/HEGIAP/), which integrates abundant analytical tools to enable global, multidimensional interpretation of gene essentiality. Our study provides new insights that improve the understanding of human essential genes.

Cancer is rarely the straightforward consequence of an abnormality in a single gene, but rather reflects a complex interplay of many genes, represented as gene modules. Here, we leverage the recent advances of model-agnostic interpretation approach and develop CGMega, an explainable and graph attention-based deep learning framework to perform cancer gene module dissection. CGMega outperforms current approaches in cancer gene prediction, and it provides a promising approach to integrate multi-omics information. We apply CGMega to breast cancer cell line and acute myeloid leukemia (AML) patients, and we uncover the high-order gene module formed by ErbB family and tumor factors NRG1, PPM1A and DLG2. We identify 396 candidate AML genes, and observe the enrichment of either known AML genes or candidate AML genes in a single gene module. We also identify patient-specific AML genes and associated gene modules. Together, these results indicate that CGMega can be used to dissect cancer gene modules, and provide high-order mechanistic insights into cancer development and heterogeneity.

The Cancer Genome Atlas (TCGA) is a publicly funded project that aims to catalog and discover major cancer-causing genomic alterations with the goal of creating a comprehensive ‘atlas’ of cancer genomic profiles. The availability of this genome-wide information provides an unprecedented opportunity to expand our knowledge of tumourigenesis. Computational analytics and mining are frequently used as effective tools for exploring this byzantine series of biological and biomedical data. However, some of the more advanced computational tools are often difficult to understand or use, thereby limiting their application by scientists who do not have a strong computational background. Hence, it is of great importance to build user-friendly interfaces that allow both computational scientists and life scientists without a computational background to gain greater biological and medical insights. To that end, this survey was designed to systematically present available Web-based tools and facilitate the use TCGA data for cancer research.