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.

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.

The intestinal microbiota is significantly affected by the external environment, but our understanding of the effects of extreme environments such as plateaus is far from adequate. In this study, we systematically analyzed the variation in the intestinal microbiota and 76 blood clinical indexes among 393 healthy adults with different plateau living durations (Han individuals with no plateau living, with plateau living for 4 to 6 days, with plateau living for >3 months, and who returned to the plain for 3 months, as well as plateau-living Tibetans). The results showed that the high-altitude environment rapidly (4 days) and continually (more than 3 months) shaped both the intestinal microbiota and clinical indexes of the Han population. With prolongation of plateau living, the general characteristics of the intestinal microbiota and clinical indexes of the Han population were increasingly similar to those of the Tibetan population. The intestinal microbiota of the Han population that returned to the plain area for 3 months still resembled that of the plateau-living Han population rather than that of the Han population on the plain. Moreover, clinical indexes such as blood glucose were significantly lower in the plateau groups than in the nonplateau groups, while the opposite result was obtained for testosterone. Interestingly, there were Tibetan-specific correlations between glucose levels and Succinivibrio and Sarcina abundance in the intestine. The results of this study suggest that a hypoxic environment could rapidly and lastingly affect both the human intestinal microbiota and blood clinical indexes, providing new insights for the study of plateau adaptability. IMPORTANCE The data presented in the present study demonstrate that the hypoxic plateau environment has a profound impact on the gut microbiota and blood clinical indexes in Han and Tibetan individuals. The plateau-changed signatures of the gut microbiota and blood clinical indexes were not restored to the nonplateau status in the Han cohorts, even when the individuals returned to the plain from the plateau for several months. Our study will improve the understanding of the great impact of hypoxic environments on the gut microbiota and blood clinical indexes as well as the adaptation mechanism and intervention targets for plateau adaptation.

Enhancer RNAs (eRNAs) are a novel class of non-coding RNA (ncRNA) molecules transcribed from the DNA sequences of enhancer regions. Despite extensive efforts devoted to revealing the potential functions and underlying mechanisms of eRNAs, it remains an open question whether eRNAs are mere transcriptional noise or relevant biologically functional species. Here, we identified a catalogue of eRNAs in a broad range of human cell/tissue types and extended our understanding of eRNAs by demonstrating their multi-omic signatures. Gene Ontology (GO) analysis revealed that eRNAs play key roles in human cell identity. Furthermore, we detected numerous known and novel functional RNA structures within eRNA regions. To better characterize the cis-regulatory effects of non-coding variation in these structural ncRNAs, we performed a comprehensive analysis of the genetic variants of structural ncRNAs in eRNA regions that are associated with inflammatory autoimmune diseases. Disease-associated variants of the structural ncRNAs were disproportionately enriched in immune-specific cell types. We also identified riboSNitches in lymphoid eRNAs and investigated the potential pathogenic mechanisms by which eRNAs might function in autoimmune diseases. Collectively, our findings offer valuable insights into the function of eRNAs and suggest that eRNAs might be effective diagnostic and therapeutic targets for human diseases.

Lnc2Catlas (http://lnc2catlas.bioinfotech.org/) is an atlas of long noncoding RNAs (lncRNAs) associated with cancer risk. LncRNAs are a class of functional noncoding RNAs with lengths over 200 nt and play a vital role in diverse biological processes. Increasing evidence shows that lncRNA dysfunction is associated with many human cancers/diseases. It is therefore important to understand the underlying relationship between lncRNAs and cancers. To this end, we developed Lnc2Catlas to compile quantitative associations between lncRNAs and cancers using three computational methods, assessing secondary structure disruption, lncRNA-protein interactions, and co-expression networks. Lnc2Catlas was constructed based on 27,670 well-annotated lncRNAs, 31,749,216 SNPs, 1,473 cancer-associated proteins, and 10,539 expression profiles of 33 cancers from The Cancer Genome Atlas (TCGA). Lnc2Catlas contains 247,124 lncRNA-SNP pairs, over two millions lncRNA-protein interactions, and 6,902 co-expression clusters. We deposited Lnc2Catlas on Alibaba Cloud and developed interactive, mobile device-compatible, user-friendly interfaces to help users search and browse Lnc2Catlas with ultra-low latency. Lnc2Catlas can aid in the investigation of associations between lncRNAs and cancers and can provide candidate lncRNAs for further experimental validation. Lnc2Catlas will facilitate an understanding of the associations between lncRNAs and cancer and will help reveal the critical role of lncRNAs in cancer.

Motivation During development of the mammalian embryo, histone modification H3K4me3 plays an important role in regulating gene expression and exhibits extensive reprograming on the parental genomes. In addition to these dramatic epigenetic changes, certain unchanging regulatory elements are also essential for embryonic development. Results Using large-scale H3K4me3 chromatin immunoprecipitation sequencing data, we identified a form of H3K4me3 that was present during all eight stages of the mouse embryo before implantation. This ‘stable H3K4me3’ was highly accessible and much longer than normal H3K4me3. Moreover, most of the stable H3K4me3 was in the promoter region and was enriched in higher chromatin architecture. Using in-depth analysis, we demonstrated that stable H3K4me3 was related to higher gene expression levels and transcriptional initiation during embryonic development. Furthermore, stable H3K4me3 was much more active in blood tumor cells than in normal blood cells, suggesting a potential mechanism of cancer progression. Supplementary information Supplementary data are available at Bioinformatics online.

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Purpose: We evaluated the long-term effect of a smartphone-facilitated home-based cardiac rehabilitation (HBCR) model in revascularized patients with coronary heart disease (CHD) on major adverse cardiac events (MACE), and secondary outcomes, including safety, quality of life, and physical capacity.Methods: It was a prospective observational cohort study including a total of 335 CHD patients after successful percutaneous coronary intervention (PCI) referred to the CR clinic in China between July 23, 2015 and March 1, 2018. Patients were assigned to two groups: HBCR tailored by monitoring and telecommunication via smartphone app (WeChat) (HBCR group, n = 170) or usual care (control group, n = 165), with follow-up for up to 42 months. Propensity score matching was conducted to match patients in the HBCR group with those in the control group. The patients in the HBCR group received educational materials weekly and individualized exercise prescription monthly, and the control group only received 20-min education at baseline in the CR clinic. The primary outcome was MACE, analyzed by Cox regression models. The changes in the secondary outcomes were analyzed by paired t-test among the matched cohort.Results: One hundred thirty-five HBCR patients were matched with the same number of control patients. Compared to the control group, the HBCR group had a much lower incidence of MACE (1.5 vs. 8.9%, p = 0.002), with adjusted HR = 0.21, 95% CI 0.07–0.85, and also had reduced unscheduled readmission (9.7 vs. 23.0%, p = 0.002), improved exercise capacity [maximal METs (6.2 vs. 5.1, p = 0.002)], higher Seattle Angina Questionnaire score, and better control of risk factors.Conclusions: The Chinese HBCR model using smartphone interaction is a safe and effective approach to decrease cardiovascular risks of patients with CHD and improve patients' wellness.Clinical Trial Registration:http://www.chictr.org.cn, identifier: ChiCTR1800015042.