PANTHER functional Analysis Use Case

The PANTHER database (Protein ANalysis THrough Evolutionary Relationships) contains comprehensive information on the evolution and function of protein-coding genes from 104 completely sequenced genomes1. PANTHER software tools allow users to classify new protein sequences, and to analyze gene lists obtained from large-scale genomics experiments2. Click here for more details about the PANTHER tools.

A more streamlined workflow has been built within the BDDS framework to analyze large-scale genomic data, especially GWAS and other genotype data. The outline of the workflow is summarized below.

• The input data can be large-scale genomic data stored in the BDDS data repository or the output of other BDDS tools, such as those in the association studies.
• The first module will check the version of the genome build from the input data, and update the chromosome coordinates to those in the latest genome build.
• A second module will convert the input data to VCF file format.
• The data is then sent to the PANTHER webservice, which supports VCF file format.
• The webservice also requires a specified annotation dataset for the analysis. Currently, PANTHER supports the following annotation datasets.
• Gene Ontology (biological process, cellular component, and molecular function)
• PANTHER pathway
• Reactome pathway
• The PANTHER system will perform statistical analysis on the data. There are two tests that can be chosen by the user (specified through webservice). Please refer to our publication in Nature Protocol for more details of the tools2.
• Overrepresentation test – This test is to determine if any function (e.g., a GO biological process or a pathway) is overrepresented in the uploaded data. Binomial distribution is the statistical algorithm behind this test.
• Enrichment test – This test determines whether numeric values associated with any ontology class or pathway are nonrandomly distributed. Mann-Whitney U test is the statistical algorithm behind this test.
• The last module of the workflow receives the results of the analysis and saves them in the BDDS repository.

References

1. Mi. H, et. al. (2017) PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements. Nucleic Acids Res 45 (D1): D183-D189.
2. Mi H., et. al. (2013) Large-scale gene function analysis with the PANTHER classification system. Nature Protocols 8, 1551–1566.