PANTHER: Making genome‐scale phylogenetics accessible to all

Abstract

Phylogenetics is a powerful tool for analyzing protein sequences, by inferring their evolutionary relationships to other proteins. However, phylogenetics analyses can be challenging: they are computationally expensive and must be performed carefully in order to avoid systematic errors and artifacts. Protein Analysis THrough Evolutionary Relationships (PANTHER; http://pantherdb.org) is a publicly available, user‐focused knowledgebase that stores the results of an extensive phylogenetic reconstruction pipeline that includes computational and manual processes and quality control steps. First, fully reconciled phylogenetic trees (including ancestral protein sequences) are reconstructed for a set of “reference” protein sequences obtained from fully sequenced genomes of organisms across the tree of life. Second, the resulting phylogenetic trees are manually reviewed and annotated with function evolution events: inferred gains and losses of protein function along branches of the phylogenetic tree. Here, we describe in detail the current contents of PANTHER, how those contents are generated, and how they can be used in a variety of applications. The PANTHER knowledgebase can be downloaded or accessed via an extensive API. In addition, PANTHER provides software tools to facilitate the application of the knowledgebase to common protein sequence analysis tasks: exploring an annotated genome by gene function; performing “enrichment analysis” of lists of genes; annotating a single sequence or large batch of sequences by homology; and assessing the likelihood that a genetic variant at a particular site in a protein will have deleterious effects.

The ubiquitin conjugase Rad6 mediates ribosome pausing during oxidative stress

“…Volcano plots were generated by using ggplot2 in Rstudio (Wickham, 2016). Gene ontology analysis was performed by using PANTHER Classification System (http://www.pantherdb.org/) (Mi et al, 2013; Thomas et al, 2022) with following parameters: PANTHER version 17.0 Overrepresentation Test, FISHER test with FDR correction, PANTHER GO-Slim Biological Process with Saccharomyces Cerevisiae - REFLIST (6050) as a reference gene list. Gcn4-target mRNAs were obtained from a published ChIP-seq dataset (Rawal et al, 2018).…”

Characterization of Arabidopsis Post-Glycosylphosphatidylinositol Attachment to Proteins Phospholipase 3 Like Genes

“…PGAP2, which acts after PGAP3, is involved in GPI anchor reacylation in mammals and there is evidence that PGAP2 and PGAP3 may form a complex. Nevertheless, as two or more PGAP3 isoforms have been identified in most plant species (Supplementary Table 3) (Thomas et al, 2021), it is exciting to think that these isoforms may reflect differences in plant GPI anchors. To address a major gap in knowledge of key importance, it would be essential to solve other plant GPI-AP structures and gain better understanding of plant GPI biology.…”

SHEPHARD: a modular and extensible software architecture for analyzing and annotating large protein datasets

“…Various annotations were used for the analysis performed here. These include proteome-wide sequence information provided from UniProt 8 , structural predictions from AlphaFold2 5,22 , post-translational modification data from ProteomeScout 23 , and gene ontology data from PANTHER 24 . In addition, protein abundance data were obtained for several different organisms, including humans 25 , A. thaliana 26 , D. melongaster 27 , E. coli 28,29 , S. pombe 30 , and S. cerevisiae 31,32 .…”