PANTHER: A Library of Protein Families and Subfamilies Indexed by Function

Abstract

In the genomic era, one of the fundamental goals is to characterize the function of proteins on a large scale. We describe a method, PANTHER, for relating protein sequence relationships to function relationships in a robust and accurate way. PANTHER is composed of two main components: the PANTHER library (PANTHER/LIB) and the PANTHER index (PANTHER/X). PANTHER/LIB is a collection of “books,” each representing a protein family as a multiple sequence alignment, a Hidden Markov Model (HMM), and a family tree. Functional divergence within the family is represented by dividing the tree into subtrees based on shared function, and by subtree HMMs. PANTHER/X is an abbreviated ontology for summarizing and navigating molecular functions and biological processes associated with the families and subfamilies. We apply PANTHER to three areas of active research. First, we report the size and sequence diversity of the families and subfamilies, characterizing the relationship between sequence divergence and functional divergence across a wide range of protein families. Second, we use the PANTHER/X ontology to give a high-level representation of gene function across the human and mouse genomes. Third, we use the family HMMs to rank missense single nucleotide polymorphisms (SNPs), on a database-wide scale, according to their likelihood of affecting protein function.

Born blonde: a recessive loss‐of‐function mutation in the melanocortin 1 receptor is associated with cream coat coloration in Antarctic fur seals

“…The resulting subPSEC score was −3.97, which exceeds the cut‐off value of −3 proposed for identifying mutations that impair protein function (Thomas et al. 2003). The corresponding probability of the variant adversely affecting protein function ( P deleterious ) was high at 0.72.…”

“…The subPSEC score of −3.97 falls well below the cut‐off of −3 for damaging mutations (Thomas et al. 2003) and the corresponding probability of the substitution being deleterious for protein function is high ( P deletirious =  0.72). PANTHER has previously been shown to accurately predict the damaging nature of Mendelian‐inherited traits that are due to a single amino acid change in the encoded protein, as is the case in our study (Thomas and Kejariwal 2004).…”

Pharmacogenomics of infliximab treatment using peripheral blood cells of patients with rheumatoid arthritis

“…To interpret our data after significance analysis of microarray analysis, we applied PANTHER Classification System (Applied Biosystems, Foster City, CA, USA) at http://PANTHER.appliedbiosystem.com. 35,36 This analysis uses the binomial statistics tool to compare the list of significantly up-or downregulated genes to a reference list (NCBI Homo sapiens) to statistically determine over-or underrepresentation of PANTHER classification categories such as biological processes. A Bonferroni correction was applied to correct for multiple testing and after classification analysis a significant P-value (Po0.05) indicates that a given category may be of biological interest.…”

Distinct proteomic profiles of amphetamine self-administration transitional states

“…Protein accession numbers for all the proteins identified in the study were imported into the Celera Panther Database. 21,22 In Celera classifications, each protein was assigned a molecular function. Over/underrepresentation of particular classifications was accomplished with the list compare function.…”

“…21,22 Different groupings of proteins (eg all proteins identified, unchanged proteins, and proteins from the classification cluster) were compared for under-or over-representation of particular molecular functions (Figure 8). The classification grouping was found to have an under-representation of ribosomal proteins and an overabundance of actin-and cytoskeletalrelated proteins.…”