A Guide to Bioinformatics Tools and Databases

Venturing into the vast realm of bioinformatics reveals a spectrum of innovative tools and databases meticulously designed to interpret and analyze biological data. This guide provides a structured exploration into these diverse domains.

Metabolic and enzyme databases

Methylation databases

Regulatory databases

The 29 databases allow to visualize modified ribosomal nucleotides of human and several major model organisms, present resources to the identification of transcription factors, functional elements, cis-regulatory elements, interferon regulated genes, large intergenic non-coding RNAs (lincRNAs) and miRNA regulatory cascades in human diseases, Triplex Target DNA Site (TSS) with genomic regulatory sequences and signals, and RNA binding elements. The data is either from text-mining-assisted workflow, chromatin immunoprecipitation (ChIP), high-throughput datasets, Genome-Wide Association Studies (GWAS), next-generation sequencing techniques and/or predicted by computational models with annotations obtained by expert review of the scientific literature. Gene names, accession numbers, Fasta sequences, ligand ID (e.g., G4L0021), ligand name (e.g., TMPyP4), ligand activity or binding properties (e.g., Cytotoxicity), author name of ligand related literature, Ensembl ID List, tissue or cell type are examples of the possible inputs. Databases for Triplex target DNA sites provide specific search criteria, such as percent guanine content and pyrimidine interruption. The result shows a list of genes, tables, venn diagrams, scatter plot, position weight matrix for a selected motif, navigation across the motifs, and heatmaps with the target elements and biosamples.

Alternative splicing databases

In the intricate landscape of bioinformatics, 24 distinctive tools focus on analyzing the effect of alternative splicing on protein interactions and structures within the human genome. These tools delve deep into the consequences of SNVs in intron positions, offering insights into the differential splicing of introns and exons across various species. Many databases, grounded in robust molecular studies and enhanced with machine learning predictions, provide curated catalogs of alternative splicing sites and gene transcripts.

Cancer databases

A collection of 56 specialized databases offers comprehensive insights into various tumor types, human TCRs’ recognition of cancer epitopes, and the impacts of somatic mutations in human cancer. These resources enable meticulous analysis of gene-specific copy numbers in diverse tumors and offer extensive information about cancer cell lines, driver genes, and metastasis, contributing to a deeper understanding of cancer’s multifaceted nature.

Comparative databases

Within comparative databases, 31 unique tools facilitate the identification of genes associated with orthologous phenotypes across species and offer extensive comparative genomic analyses. These tools are crucial for investigating the evolutionary dynamics of genes and provide insights into non-human primate reference transcriptomes and human nonsynonymous SNPs in protein structures and metabolic networks.

Disease-specific and variant-disease association

Exploration uncovers 84 specialized tools and databases related to a spectrum of diseases, from monogenic conditions to complex ailments like Alzheimer’s and Autism. These serve as repositories for human mutations and SNVs, delivering annotated variants and their impacts, and elucidating the clinical significance of variants for a range of conditions, making them indispensable for understanding diverse human diseases.

Gene expression databases

116 diverse databases and tools are available in the realm of gene expression, providing information on transcript counts and gene expressions in varied tissue conditions. They offer insights into age, apoptosis, RNA-seq data, single-cell studies, chromatin regulators, and histone modifications. The wealth of experimental data available is presented in formats like tables, diagrams, heatmaps, bar plots, and dot plots, aiding in the comprehensive study of genes.

Genomic and sequence databases

We found 217 tools (Table S6), related to post-translational (PTM) modification sites and mutations (both germline and somatic) from multiple sources, mitochondrial sequences coming from ancient DNA samples (aDNA), disease-specific genomic data, genomic histone marks, chromatin states and motifs, chromosome annotation, evolutionary relationship of human proteins and animal models, analyses of allelic imbalance in clonal cell populations based on sequence polymorphisms. General information on genes, such as orthologs and paralogs, exon, intron and UTRs, gene classification, transcript sequences, protein sequences, mutations and SNPs, transcript cluster or selected publications can also be found. The general input is a Gene Symbol, Chromosomal position or region. The output is presented in browser visualization, tables with the genomic sequence of the interest, gene report, and heatmaps with pathogenicity of the mutations found in a sequence of the gene or region of interest.

LncRNA and miRNA databases

We found 73 tools related to miRNA and long non-conding RNAs (lncRNAs) in different organisms and pathogenic conditions. Of special interest may be data on putative antagomirs-miRNA heterodimers, protein-protein interactions (PPI) and functionally synergistic miRNA pairs (including transcription factors). The input of the search can be a Gene symbol, miRNA or LncRNA ID or target (hsa-let-7a, for example), Fasta file of the region of interest, or chromosomal location (any position in hg38 version, for example). In the case of LncRNA, the output is a table with the basic information of sequence, strand, class (antisense, for example), and conservation across species, with or without prediction scores. For miRNA, the output show information about the seed region, conservation score, accessibility, and secondary structures, minimum free energy estimation, correlations about expression, and start/end of the miRNA sequences. In disease-specific databases, the table may present the disease name, information about causality, and related literature.

Proteome and protein-protein interaction databases

We found 24 tools involving databases with information about potential cleavage sites in datasets of all human proteins collected in Uniprot and their orthologs, allowing for tracing of cleavage motif conservation, bioactive molecules, human metabolites, natural products, patented agents and other molecules. Databases are organized as disease-specific, tissue-specific, organelle-related or by protein families. Epigenetic enzymes and chemical modulators focused on epigenetic therapeutics, as well as functional databases including information from cells and tissues at a variety of physiological conditions, are also available. The input of the analyses is either a GO term, gene symbol or name, chromosomal location, metabolite or molecule name, or enzyme family name. Compartment and subsystem 2D maps, tables with literature related, enzyme domains, Uniprot ID, plots of classic or multivariate ROC curves, and images illustrating predicted small molecules are present in the output.

Other databases

A total of 64 databases are available, focusing on various aspects of immunogenetics. These databases offer a comprehensive understanding of cytokine receptors, their ligands, involvement in diseases, and their applications in clinical treatments. They house intricate details about human Major Histocompatibility Complex (MHC) genes, peptides, predictions, and proteins related to human leukocyte antigen (HLA) I and HLA II-restricted peptides. Additionally, they provide extensive literature about immunoproteins, tumor T cell antigens, and in silico predictions of epitopes.

Reference

Villalba, G. C., & Matte, U. (2021). Fantastic databases and where to find them: Web applications for researchers in a rush. Genetics and Molecular Biology, 44, e20200203.