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Many bioinformatics resources with unique perspectives on the protein landscape are currently available. However, generating new knowledge from these resources requires interoperable workflows that support cross-resource queries. In this study, we employ federated queries linking information from the Protein Kinase Ontology, iPTMnet, Protein Ontology, neXtProt, and the Mouse Genome Informatics to identify key knowledge gaps in the functional coverage of the human kinome and prioritize understudied kinases, cancer variants and post-translational modifications (PTMs) for functional studies. We identify 32 functional domains enriched in cancer variants and PTMs and generate mechanistic hypotheses on overlapping variant and PTM sites by aggregating information at the residue, protein, pathway and species level from these resources. We experimentally test the hypothesis that S768 phosphorylation in the C-helix of EGFR is inhibitory by showing that oncogenic variants altering S768 phosphorylation increase basal EGFR activity. In contrast, oncogenic variants altering conserved phosphorylation sites in the 'hydrophobic motif' of PKCβII (S660F and S660C) are loss-of-function in that they reduce kinase activity and enhance membrane translocation. Our studies provide a framework for integrative, consistent, and reproducible annotation of the cancer kinomes.
Pubmed ID: 29695735
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Public bibliographic database that provides access to citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. PubMed citations and abstracts include fields of biomedicine and health, covering portions of life sciences, behavioral sciences, chemical sciences, and bioengineering. Provides access to additional relevant web sites and links to other NCBI molecular biology resources. Publishers of journals can submit their citations to NCBI and then provide access to full-text of articles at journal web sites using LinkOut.
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Database to store and display somatic mutation information and related details and contains information relating to human cancers. The mutation data and associated information is extracted from the primary literature. In order to provide a consistent view of the data a histology and tissue ontology has been created and all mutations are mapped to a single version of each gene. The data can be queried by tissue, histology or gene and displayed as a graph, as a table or exported in various formats.
Some key features of COSMIC are:
* Contains information on publications, samples and mutations. Includes samples which have been found to be negative for mutations during screening therefore enabling frequency data to be calculated for mutations in different genes in different cancer types.
* Samples entered include benign neoplasms and other benign proliferations, in situ and invasive tumours, recurrences, metastases and cancer cell lines.
A database of protein families, each represented by multiple sequence alignments and hidden Markov models (HMMs). Users can analyze protein sequences for Pfam matches, view Pfam family annotation and alignments, see groups of related families, look at the domain organization of a protein sequence, find the domains on a PDB structure, and query Pfam by keywords. There are two components to Pfam: Pfam-A and Pfam-B. Pfam-A entries are high quality, manually curated families that may automatically generate a supplement using the ADDA database. These automatically generated entries are called Pfam-B. Although of lower quality, Pfam-B families can be useful for identifying functionally conserved regions when no Pfam-A entries are found. Pfam also generates higher-level groupings of related families, known as clans (collections of Pfam-A entries which are related by similarity of sequence, structure or profile-HMM).
View all literature mentionsHuman protein knowledge platform. Knowledge platform for human proteins selects and filters high throughput data pertinent to human proteins from UniProtKB. Extends UniProtKB/Swiss-Prot annotations for human proteins to include several new data types.
View all literature mentionsSoftware package as multiple alignment program for amino acid or nucleotide sequences. Can align up to 500 sequences or maximum file size of 1 MB. First version of MAFFT used algorithm based on progressive alignment, in which sequences were clustered with help of Fast Fourier Transform. Subsequent versions have added other algorithms and modes of operation, including options for faster alignment of large numbers of sequences, higher accuracy alignments, alignment of non-coding RNA sequences, and addition of new sequences to existing alignments.
View all literature mentionsA protein database which connects multiple disparate bioinformatics tools and systems text mining, data mining, analysis and visualization tools, and databases and ontologies.
View all literature mentionsSoftware designed for single or multi-wavelength intracellular ion measurements. It provides simultaneous display of raw data, ratio image, graphs of intensities, ratios, ion concentrations, and a non-ratiometric image such as a brightfield or phase-contrast image. Two different ratiometric indicators can be imaged and measured simultaneously to provide greater insight to ion exchange and intracellular function regardless of dye loading concentrations, conditions, or emission intensities.
View all literature mentionsA vector graphics software which runs on Windows, Mac OS X and GNU/Linux. It can import and export various file formats, including SVG, AI, EPS, PDF, PS and PNG. Features include object creation, object manipulation, color editing, and text editing.
View all literature mentionsCell line COS-7 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)
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