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Codon-level information improves predictions of inter-residue contacts in proteins by correlated mutation analysis.

Etai Jacob | Ron Unger | Amnon Horovitz
eLife | 2015

Methods for analysing correlated mutations in proteins are becoming an increasingly powerful tool for predicting contacts within and between proteins. Nevertheless, limitations remain due to the requirement for large multiple sequence alignments (MSA) and the fact that, in general, only the relatively small number of top-ranking predictions are reliable. To date, methods for analysing correlated mutations have relied exclusively on amino acid MSAs as inputs. Here, we describe a new approach for analysing correlated mutations that is based on combined analysis of amino acid and codon MSAs. We show that a direct contact is more likely to be present when the correlation between the positions is strong at the amino acid level but weak at the codon level. The performance of different methods for analysing correlated mutations in predicting contacts is shown to be enhanced significantly when amino acid and codon data are combined.

Pubmed ID: 26371555

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This is a list of tools and resources that we have found mentioned in this publication.


Ensembl (tool)

RRID:SCR_002344

Collection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. Used to automatically annotate genome, integrate this annotation with other available biological data and make data publicly available via web. Ensembl tools include BLAST, BLAT, BioMart and the Variant Effect Predictor (VEP) for all supported species.

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UniProt (tool)

RRID:SCR_002380

Collection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.

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RefSeq (tool)

RRID:SCR_003496

Collection of curated, non-redundant genomic DNA, transcript RNA, and protein sequences produced by NCBI. Provides a reference for genome annotation, gene identification and characterization, mutation and polymorphism analysis, expression studies, and comparative analyses. Accessed through the Nucleotide and Protein databases.

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European Nucleotide Archive (ENA) (tool)

RRID:SCR_006515

Public archive providing a comprehensive record of the world''''s nucleotide sequencing information, covering raw sequencing data, sequence assembly information and functional annotation. All submitted data, once public, will be exchanged with the NCBI and DDBJ as part of the INSDC data exchange agreement. The European Nucleotide Archive (ENA) captures and presents information relating to experimental workflows that are based around nucleotide sequencing. A typical workflow includes the isolation and preparation of material for sequencing, a run of a sequencing machine in which sequencing data are produced and a subsequent bioinformatic analysis pipeline. ENA records this information in a data model that covers input information (sample, experimental setup, machine configuration), output machine data (sequence traces, reads and quality scores) and interpreted information (assembly, mapping, functional annotation). Data arrive at ENA from a variety of sources including submissions of raw data, assembled sequences and annotation from small-scale sequencing efforts, data provision from the major European sequencing centers and routine and comprehensive exchange with their partners in the International Nucleotide Sequence Database Collaboration (INSDC). Provision of nucleotide sequence data to ENA or its INSDC partners has become a central and mandatory step in the dissemination of research findings to the scientific community. ENA works with publishers of scientific literature and funding bodies to ensure compliance with these principles and to provide optimal submission systems and data access tools that work seamlessly with the published literature. ENA is made up of a number of distinct databases that includes the EMBL Nucleotide Sequence Database (Embl-Bank), the newly established Sequence Read Archive (SRA) and the Trace Archive. The main tool for downloading ENA data is the ENA Browser, which is available through REST URLs for easy programmatic use. All ENA data are available through the ENA Browser. Note: EMBL Nucleotide Sequence Database (EMBL-Bank) is entirely included within this resource.

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Ensembl Genomes (tool)

RRID:SCR_006773

Database portal offering integrated access to genome-scale data from non-vertebrate species of scientific interest, developed using the Ensembl genome annotation and visualization platform. Ensembl Genomes consists of five sub-portals (for bacteria, protists, fungi, plants and invertebrate metazoa) designed to complement the availability of vertebrate genomes in Ensembl. Many of the databases supporting the portal have been built in close collaboration with the scientific community - essential for maintaining the accuracy and usefulness of the resource. A common set of user interfaces (which include a graphical genome browser, FTP, BLAST search, a query optimized data warehouse, programmatic access, and a Perl API) is provided for all domains. Data types incorporated include annotation of (protein and non-protein coding) genes, cross references to external resources, and high throughput experimental data (e.g. data from large scale studies of gene expression and polymorphism visualized in their genomic context). Additionally, extensive comparative analysis has been performed, both within defined clades and across the wider taxonomy, and sequence alignments and gene trees resulting from this can be accessed through the site.

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European Molecular Biology Laboratory (tool)

RRID:SCR_004473

Intergovernmental organisation funded by public research money from its member states in Europe. Groups and laboratories perform basic research in molecular biology and molecular medicine, training for scientists, students and visitors. Provides development of services, new instruments and methods, data and technology in its member states.

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SOURCE (tool)

RRID:SCR_005799

SOURCE compiles information from several publicly accessible databases, including UniGene, dbEST, UniProt Knowledgebase, GeneMap99, RHdb, GeneCards and LocusLink. GO terms associated with LocusLink entries appear in SOURCE. The mission of SOURCE is to provide a unique scientific resource that pools publicly available data commonly sought after for any clone, GenBank accession number, or gene. SOURCE is specifically designed to facilitate the analysis of large sets of data that biologists can now produce using genome-scale experimental approaches Platform: Online tool

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CRAN (tool)

RRID:SCR_003005

Network of ftp and web servers around world that store identical, up to date, versions of code and documentation for R. Package archive network for R programming language.

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Pfam (tool)

RRID:SCR_004726

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).

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EMBOSS (tool)

RRID:SCR_008493

Software analysis package for molecular biology community. Automatically copes with data in variety of formats and allows transparent retrieval of sequence data from web. Libraries are provided with package. Provides toolkit for creating bioinformatics applications or workflows. Provides set of sequence analysis programs. Provided programs cover areas such as sequence alignment, rapid database searching with sequence patterns, protein motif identification, nucleotide sequence pattern analysis, codon usage analysis for small genomes, rapid identification of sequence patterns in large scale sequence sets, and presentation tools for publication.

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