MutRank: an R shiny web-application for exploratory targeted mutual rank-based coexpression analyses integrated with user-provided supporting information

The rapid assignment of genotypes to phenotypes has been a historically challenging process. The discovery of genes encoding biosynthetic pathway enzymes for defined plant specialized metabolites has been informed and accelerated by the detection of gene clusters. Unfortunately, biosynthetic pathway genes are commonly dispersed across chromosomes or reside in genes clusters that provide little predictive value. More reliably, transcript abundance of genes underlying biochemical pathways for plant specialized metabolites display significant coregulation. By rapidly identifying highly coexpressed transcripts, it is possible to efficiently narrow candidate genes encoding pathway enzymes and more easily predict both functions and functional associations. Mutual Rank (MR)-based coexpression analyses in plants accurately demonstrate functional associations for many specialized metabolic pathways; however, despite the clear predictive value of MR analyses, the application is uncommonly used to drive new pathway discoveries. Moreover, many coexpression databases aid in the prediction of both functional associations and gene functions, but lack customizability for refined hypothesis testing. To facilitate and speed flexible MR-based hypothesis testing, we developed MutRank, an R Shiny web-application for coexpression analyses. MutRank provides an intuitive graphical user interface with multiple customizable features that integrates user-provided data and supporting information suitable for personal computers. Tabular and graphical outputs facilitate the rapid analyses of both unbiased and user-defined coexpression results that accelerate gene function predictions. We highlight the recent utility of MR analyses for functional predictions and discoveries in defining two maize terpenoid antibiotic pathways. Beyond applications in biosynthetic pathway discovery, MutRank provides a simple, customizable and user-friendly interface to enable coexpression analyses relating to a breadth of plant biology inquiries. Data and code are available at GitHub: https://github.com/eporetsky/MutRank.

Protein Complex Discovery by Interaction Filtering from Protein Interaction Networks Using Mutual Rank Coexpression and Sequence Similarity

The evaluation of the biological networks is considered the essential key to understanding the complex biological systems. Meanwhile, the graph clustering algorithms are mostly used in the protein-protein interaction (PPI) network analysis. The complexes introduced by the clustering algorithms include noise proteins. The error rate of the noise proteins in the PPI network researches is about 40–90%. However, only 30–40% of the existing interactions in the PPI databases depend on the specific biological function. It is essential to eliminate the noise proteins and the interactions from the complexes created via clustering methods. We have introduced new methods of weighting interactions in protein clusters and the splicing of noise interactions and proteins-based interactions on their weights. The coexpression and the sequence similarity of each pair of proteins are considered the edge weight of the proteins in the network. The results showed that the edge filtering based on the amount of coexpression acts similar to the node filtering via graph-based characteristics. Regarding the removal of the noise edges, the edge filtering has a significant advantage over the graph-based method. The edge filtering based on the amount of sequence similarity has the ability to remove the noise proteins and the noise interactions.