A-to-I RNA editing, constituting nearly 90% of all RNA editing events in human, has been reported to involve in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's diseases. Its editing divergences were studied recently which may be partially attributed to genetic variations. To date, the contributions of genetic polymorphisms to A-to-I RNA editing in neurodegenerative diseases have not been deeply and comprehensively investigated. Here, we built NeuroEdQTL, which is available at https://relab.xidian.edu.cn/NeuroEdQTL/, aiming to provide a resource and reference for the regulations of genetic variations on A-to-I RNA editing events in human to uncover some neurodegeneration-associated mechanisms. To do this, we performed large-scale and genome-wide identification of RNA editing quantitative trait locus (edQTLs) across 9 brain tissues from AMP-AD (Accelerating Medicines Partnership - Alzheimer's Disease) and blood samples from PPMI (Parkinson's Progression Markers Initiative). For these edQTLs, we investigated their contributions on RNA editing events. Moreover, we performed functional annotations of these edQTLs from five aspects below, including RNA editing QTLs and central dogma, RNA editing QTLs associated with diseases, RNA editing QTLs associated with regulator events, RNA editing QTLs associated with cellular events with editing as mediators, and RNA editing QTLs associated with Drugs. NeuroEdQTL is an important component of RNA editing regulators and will be a unique resource for the study of neurodegenerative diseases. It can be used for understanding the tumorigenesis of genetic variations through the potential regulations of neurodegeneration -related RNA editing events.

Alternative polyadenylation (APA) is an important post-transcript regulation process that can regulate gene expression by generating mRNA isoforms with different 3’UTR length. Disrupted APA is frequently involved in tumorigenesis and cancer progression through regulating gene expression of oncogene and tumor suppressors. To date, systematic and intensive functional annotation and downstream analysis for APA events in cancer are not available. Here, we construct CAFuncAPA (systematic functional annotation of APA events in human cancers). Aiming to provide comprehensive and systematical functional annotation resource for APA events in cancer.

AgeAnno is a comprehensive and curated database, aiming to provide comprehensive characterizations for aging-related genes across diverse tissue-cell types in human by using single-cell RNA and ATAC sequencing data (scRNA and scATAC). The current version of AgeAnno houses 1 678 610 cells from 28 healthy tissue samples with ages ranging from 0 to 110 years. We collected 5 580 aging-related genes from previous resources and performed dynamic functional annotations of the cellular context. For the scRNA data, we performed analyses include differential gene expression, gene variation coefficient, cell communication network, transcription factor (TF) regulatory network, and immune cell proportionc. AgeAnno also provides differential chromatin accessibility analysis, motif/TF enrichment and footprint analysis, and co-accessibility peak analysis for scATAC data. We also provide diseases and drugs for aging-related genes. AgeAnno will be a unique resource to systematically characterize aging-related genes across diverse tissue-cell types in human, and it could facilitate antiaging and aging-related disease research.

A-to-I RNA editing contributes to nearly 90% of all editing events in human. It is catalyzed by specific adenosine deaminase (ADAR) which binds to double-stranded RNA (dsRNA) motifs. The main and probably ancestral role of these editing events is to prevent dsRNA triggering an innate immune response mediated by melanoma differentiation-associated protein 5 (MDA5). The links between the editing of genes and immune response remain to be studied for their contributions to pathogenesis, progression, and treatment of cancer. Here, we built ImmuneEditome, aiming to provide a resource and reference for the functional annotation of enriched editing regions (EERs) with cancer immunity. We identified 17,689 EERs in 11,052 samples across 33 cancer types from the TCGA database (The Cancer Genome Atlas). For these EER-associated genes (EAGs, 7,818), we performed multiple functional annotations. These include studies of their preferred genomic locations, tumor-specific properties, potential roles with cancer immunity, and possible effects on drug sensitivity. The immune studies reveal the associations of EERs/EAGs with immune infiltration, immune gene set scores, immune genes, and immune splicing events. All these analyses archived in ImmuneEditome will uncover the functions of RNA editing with cancer immunity, providing a novel knowledgebase for tumor immune therapy.

Aging is a complex process characterized by the progressive decline in various biological systems at molecular, cellular, tissue, and organ levels. To understand the underlying mechanisms, twelve hallmarks have been identified as common factors contributing to aging. These hallmarks are demonstrated to be remarkable conservation across multiple species. Understanding the regulation of aging factors and their relationships across species can facilitate the translation of anti -aging drug development from model organisms to humans. Here, we built AgeAnnoMO, a knowledgebase of multi-omics annotation for animal aging. AgeAnnoMO encompasses an extensive collection of 136 datasets from eight modalities, encompassing 8,586 samples from 50 representative species, making it a comprehensive resource for aging and longevity research. AgeAnnoMO characterizes multiple aging regulators across species via multi-omics data, comprehensively annotating aging-related genes, aging-related proteins, metabolites, mitochondrial genes, microbiotas, and age-specific TCR and BCR sequences tied to aging hallmarks for these species and tissues. We anticipate that AgeAnnoMO will provide a valuable resource for comprehending and integrating the conserved driving hallmarks in aging biology, and identifying the targetable biomarkers for aging research.