1. Introduction

1.1 Backgroud

The brain is the control center for the body. It has specific regions that do certain types of work, including frontal lobe, parietal lobe, temporal lobe, occipital lobe and cerebellum. All of your senses – sight, smell, hearing, touch, and taste – depend on your brain.

When the brain is damaged, it can affect many things. There is a broad category of brain diseases, which vary greatly in symptoms and severity, such as brain injuries, brain tumors and neurodegenerative diseases. Among the brain diseases, glioma is one of the most common malignant brain tumors and exhibits low resection rate and high recurrence risk.

Comprehensive integration of multi-omics data and annotation of brain-specific genes, brain-region-specific genes and brain diseases on the molecular level will assist us to elucidate the mechanism of brain diseases. Although a number of brain-disease associated databases have been created, they lack detailed annotation information or omics datasets, posing great challenges for better understanding the molecular functional significance in brain diseases.

1.2 Our Mission

Here we present BrainBase (https://bigd.big.ac.cn/brainbase), a knowledgebase of brain diseases. As one of the resources in the National Genomics Data Center of China, BrainBase is devoted to providing a comprehensive annotation of brain diseases on molecular level (mRNA, lncRNA, miRNA, protein and CpG site) with high-quality articles and particularly, it provides the analyzed glioma multi-omics figures/tables. Users can perform multi-omics analyses such as survival analysis and differential analysis among different glioma grades or subtypes.

3. Brain Disease Knowledge

3.1 Glioma and medulloblastoma

The glioma and medulloblastoma publications are collected from PubMed with the criterion of literature “IF>10” and keywords “glioma” or “medulloblastoma”. We create a curation model for these two brain tumors, which covers omics level, associated pathways, tumor cell state and description, PMID and journal information, omics level, etc.

3.2 Curation model

    1) Which omics level the associated gene influence the disease: genome, epigenome, transcriptome and proteome

    2) What regulate the gene and the gene influence what: Upstream: regulator type, regulator, interaction and direction Downstream: target type, target, interaction and effect

    3) Pathway: The pathway of the gene and molecular effect

    4) Tumor cell state: How the molecular influence the tumor cell state and detailed description

    5) Sample information: sample species and source (tissue/cell line)

    6) Disease information: classification, subtype, grade and the potential of the molecular (diagnosis, prognosis, predictive and therapy)

    7) Literature information: PMID, title, journal ,year, authors, corresponding author and email

3.3 Controled vocabulary

Data type Value
genomics Mutation; Wildtype; Copy number variation; Gene fusion
epigenetics DNA; RNA; Histone
transcriptomics up-regulated; down-regulated; activated; inhibited; alternative splicing
proteomics up-regulated; down-regulated; activated; inhibited; overexpressed
regulator type protein; mRNA; miRNA; pathway; lncRNA; virus
interaction binding; coexpression
direction promote; activate; inhibit; cooperation; co-target
target type protein; mRNA; miRNA; pathway; lncRNA; signaling; telomere
effect co-active; inhibit; activate; promote; methylate; phosphorylate; demethylation; forming complex
grade G2; G3; G4
classification Glioma; Glioblastoma; Medulloblastoma
subtype Adult glioblastoma; Adult anaplastic oligodendroglioma; Astrocytoma; Angiocentric Glioma; Anaplastic oligodendroglioma; Brainstem glioma Chordoid glioma; Classical Glioblastoma; CML glioblastomaDiffuse glioma; Diffuse intrinsic pontine glioma (DIPG); Early gliomagenesis; Ependymoma Glioblastoma; Glioblastoma multiforme; High-grade glioma; Low-grade glioma; MES glioblastoma; PN glioblastoma; Proneural glioblastomag
tumor cell state aggressive; angiogenesis; apoptosis; asymmetric division and differentiation; autophagy; clonogenicity; cell death; diffusion; expansion; formation; growth; infiltration; inhibition; invasion; maintenance; metastases; migration; oncogene capacity; proliferation; radioresistance; self-renewal; stemness; transformation; tumorigenesis; viability; promote oncogenesis; stimulated tumor vascularization
species Homo Sapiens; Mus musculus; Drosophila; Rattus norvegicus

3.4 Other brain diseases

The knowledge of other brain diseases are collected from public resources, including LncBook, EWAS Atlas, EDK, HMDD, Developmental Brain Disorders Database and Brain Disease Knowledgebase. The disease-gene association annotation with link information of the public databases mentioned above are collected. The descriptions about the diseases are mainly collected from Wikipedia and Disease Ontology.

4. Multi-omics datasets Analysis

In this study, except the knowledge annotation of brain disease, we provide the function for users to analyze the multi-omics data of glioma. The codes of figure are written by R, users can search a gene to do the survival analysis or compare the multi-omics level between different grades or subtypes of glioma on multi-omics level (genome, transcriptome, epigenome and proteome). All the analyzed figures can be browsed on the website and downloaded with a pdf format by clicking the figures on the website. The analysis types of the four omics are described below.

Genome: G2 vs G3 vs G4, IDH status, 1p19q status, IDH & 1p19q status, MGMT status and survival.

Transcriptome: Normal and Tumor tissue profile, Normal vs Glioma, G2 vs G3 vs G4, IDH status, 1p19q status, IDH & 1p19q status, MGMT status, cell type and survival.

Epigenome: Glioma vs Normal, G2 vs G3 vs G4, IDH status, IDH & 1p19q status, MGMT status and survival.