Publication

Despite accumulating evidence implicating noncoding variants in human diseases, unraveling their functionality remains a significant challenge. Systematic annotations of the regulatory landscape and the growth of sequence variant data sets have fueled the development of tools and methods to identify causal noncoding variants and evaluate their regulatory effects. Here, we review the latest advances in the field and discuss potential future research avenues to gain a more in-depth understanding of noncoding regulatory variants. Continue reading...

Enhancers are pivotal for regulating gene transcription that occurs at promoters. Identification of the interacting enhancer–promoter pairs and understanding the mechanisms behind how they interact and how enhancers modulate transcription can provide fundamental insight into gene regulatory networks. Recently, advances in high-throughput methods in three major areas—chromosome conformation capture assay, such as Hi-C to study basic chromatin architecture, ectopic reporter experiments such as self-transcribing active regulatory region sequencing (STARR-seq) to quantify promoter and enhancer activity, and endogenous perturbations such as clustered regularly interspaced short palindromic repeat interference (CRISPRi) to identify enhancer–promoter compatibility—have further our knowledge about transcription. In this review, we will discuss the major method developments and key findings from these assays. Continue reading...

Background: Adenosine-to-inosine (A-to-I) editing is an important RNA posttranscriptional process related to a multitude of cellular and molecular activities. However, systematic characterizations of whether and how the events of RNA editing are associated with the binding preferences of RNA sequences to RNA-binding proteins (RBPs) are still lacking. Results: With the RNA-seq and RBP eCLIP-seq datasets from the ENCODE project, we quantitatively survey the binding preferences of 150 RBPs to RNA editing events, followed by experimental validations. Such analyses of the RBP-associated RNA editing at nucleotide resolution and genome-wide scale shed light on the involvement of RBPs specifically in RNA editing-related processes, such as RNA splicing, RNA secondary structures, RNA decay, and other posttranscriptional processes. Conclusions: These results highlight the relevance of RNA editing in the functions of many RBPs and therefore serve as a resource for further characterization of the functional associations between various RNA editing events and RBPs. Continue reading...

Immunotherapy is one of the most promising strategies for cancer, compared with traditional treatments. As one of the key emerging immunotherapies, anti-PD-1/PD-L1 treatment has brought survival benefits to many advanced cancer patients. However, in pancreatic cancer, immunotherapy-based approaches have not achieved a favorable clinical effect because of mismatch repair deficiencies. Therefore, the majority of pancreatic tumors are regarded as immune-quiescent tumors and non-responsive to single-checkpoint blockade therapies. Many preclinical and clinical studies suggest that it is still important to clarify the regulatory mechanism of the PD-1/ PD-L1 pathway in pancreatic cancer. As a marker of cancer stem cells, DCLK1 has been found to play an important role in the occurrence and development of a plethora of human cancers. Recent researches have revealed that DCLK1 is closely related to EMT process of tumor cells, meanwhile, it could also be used as a biomarker in gastrointestinal tumors to predict the prognoses of patients. However, the role that DCLK1 plays in the immune regulation of tumor microenvironments remains unknown. Therefore, we sought to understand if DCLK1 could positively regulate the expression of PD-L1 in pancreatic cancer cells. Furthermore, we examined if DCLK1 highly correlated with the Hippo pathway through TCGA database analysis. We found that DCLK1 helped regulate the level of PD-L1 expression by affecting the corresponding expression level of yes-associated protein in the Hippo pathway. Collectively, our study identifies DCLK1 as an important regulator of PD-L1 expression in pancreatic tumor and highlights a central role of DCLK1 in the regulation of tumor immunity. Continue reading...

Each human genome carries tens of thousands of coding variants. The extent to which this variation is functional and the mechanisms by which they exert their influence remains largely unexplored. To address this gap, we leverage the ExAC database of 60,706 human exomes to investigate experimentally the impact of 2009 missense single nucleotide variants (SNVs) across 2185 protein-protein interactions, generating interaction profiles for 4797 SNV-interaction pairs, of which 421 SNVs segregate at > 1% allele frequency in human populations. We find that interaction-disruptive SNVs are prevalent at both rare and common allele frequencies. Furthermore, these results suggest that 10.5% of missense variants carried per individual are disruptive, a higher proportion than previously reported; this indicates that each individual’s genetic makeup may be significantly more complex than expected. Finally, we demonstrate that candidate disease-associated mutations can be identified through shared interaction perturbations between variants of interest and known disease mutations. Continue reading...

Background: Computational biology requires the reading and comprehension of biological data files. Plain-text formats such as SAM, VCF, GTF, PDB and FASTA, often contain critical information which is obfuscated by the data structure complexity. Results: bioSyntax is a freely available suite of biological syntax highlighting packages for vim, gedit, Sublime, VSCode, and less. bioSyntax improves the legibility of low-level biological data in the bioinformatics workspace. Conclusion: bioSyntax supports computational scientists in parsing and comprehending their data efficiently and thus can accelerate research output. Continue reading...