Applications for protein sequence–function evolution data: mRNA/protein expression analysis and coding SNP scoring tools

By Paul D. Thomas, Anish Kejariwal, Nan Guo, Huaiyu Mi, Michael J. Campbell, Anushya Muruganujan, Betty Lazareva-Ulitsky. Nucleic Acids Res., 2006

528 citations recorded by the source corpus.

The vast amount of protein sequence data now available, together with accumulating experimental knowledge of protein function, enables modeling of protein sequence and function evolution. The PANTHER database was designed to model evolutionary sequence–function relationships on a large scale. There are a number of applications for these data, and we have implemented web services that address three of them. The first is a protein classification service. Proteins can be classified, using only their amino acid sequences, to evolutionary groups at both the family and subfamily levels. Specific subfamilies, and often families, are further classified when possible according to their functions, including molecular function and the biological processes and pathways they participate in. The second application, then, is an expression data analysis service, where functional classification information can help find biological patterns in the data obtained from genome-wide experiments. The third application is a coding single-nucleotide polymorphism scoring service. In this case, information about evolutionarily related proteins is used to assess the likelihood of a deleterious effect on protein function arising from a single substitution at a specific amino acid position in the protein. All three web services are available at .

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e1624cfc69296ec928e9c320a782950aa038b4a5

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Citations in the corpus

Large-scale gene function analysis with PANTHER Classification System (2013, background): “In 2006, the first version of gene analysis tools was released 4 .”
Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. (2007, methodology): “…compared with a reference list (NCBI: Mus musculus genes, version 1-16- 2007) (Maglott et al. 2007), and significant enrichment of the experimental data set in a given process was calculated using binomial testing with Bonferroni correction for multiple testing as described (Thomas et al. 2006).”
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk (2010, unknown): “…there are intriguing possible SNP candidates: in SLC2A2 the lead SNP (rs11920090) is in perfect LD (r 2 = 1.0) with rs5400 (Stage 1 discovery association P=5.9×10 −6 ), which codes for the amino acid substitution T110I, predicted to be “possibly damaging” by PolyPhen35 and PANTHER (Pdel= 0.92)36.”
PANTHER Pathway: an ontology-based pathway database coupled with data analysis tools (2009, methodology): “PANTHER provides a number of applications and services to help our users in their research (Thomas et al. 2006).”
PANTHER version 16: a revised family classification, tree-based classification tool, enhancer regions and extensive API (2020, methodology): “The gene list analysis tools enable users to upload lists of genes or proteins and perform statistical tests to find enriched functional classes in their list (2,3).”
PANTHER version 7: improved phylogenetic trees, orthologs and collaboration with the Gene Ontology Consortium (2009, methodology): “Expanded sets of genomes and sequence identifiers for PANTHER tools Since its inception, the PANTHER website has provided, for a limited set of ‘fully supported’ genomes (human, mouse, rat and fruit fly), the following functionality: (i) stored classifications for all protein-coding genes, including”
PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements (2016, methodology): “The PANTHER website contains several data analysis tools that make use of the underlying PANTHER data (4).”
Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine (2010, methodology): “A unique set of genes with ≥1 enriched 5-hmC region was then generated and used as input for the binomial gene list comparison tool provided by the Protein Analysis Through Evolutionary Relationships (PANTHER) classification syste”
Integrative regulatory mapping indicates that the RNA-binding protein HuR (ELAVL1) couples pre-mRNA processing and mRNA stability (2011, methodology): “GO Analysis Each data setwas percentile-rank transformed (background list not necessary) and analyzed as gene expression values in PantherDB (Thomas et al., 2006).”
PANTHER version 14: more genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools (2018, methodology): “Starting in 2004, the PANTHER website has hosted two interactive tools for finding classes of genes that are enriched among the genes in a user’s input gene list, relative to a ‘reference’ gene list (from which the input list was selected) (8).”
PANTHER version 6: protein sequence and function evolution data with expanded representation of biological pathways (2006, background): “PANTHER is a publicly available database that relates protein sequence evolution to evolution of protein functions and biological roles (1,2).”