Protein function prediction from dynamic protein interaction network using gene expression data.

Computational prediction of functional annotation of proteins is an uphill task. There is an ever increasing gap between functional characterization of protein sequences and deluge of protein sequences generated by large-scale sequencing projects. The dynamic nature of protein interactions is frequently observed which is mostly influenced by any new change of state or change in stimuli. Functional characterization of proteins can be inferred from their interactions with each other, which is dynamic in nature. In this work, we have used a dynamic protein-protein interaction network (PPIN), time course gene expression data and protein sequence information for prediction of functional annotation of proteins. During progression of a particular function, it has also been observed that not all the proteins are active at all time points. For unannotated active proteins, our proposed methodology explores the dynamic PPIN consisting of level-1 and level-2 neighboring proteins at different time points, filtered by Damerau-Levenshtein edit distance to estimate the similarity between two protein sequences and coefficient variation methods to assess the strength of an edge in a network. Finally, from the filtered dynamic PPIN, at each time point, functional annotations of the level-2 proteins are assigned to the unknown and unannotated active proteins through the level-1 neighbor, following a bottom-up strategy. Our proposed methodology achieves an average precision, recall and F-Score of 0.59, 0.76 and 0.61 respectively, which is significantly higher than the reported state-of-the-art methods.

Protein function prediction from protein-protein interaction network using gene ontology based neighborhood analysis and physico-chemical features.

Protein Function Prediction from Protein-Protein Interaction Network (PPIN) and physico-chemical features using the Gene Ontology (GO) classification are indeed very useful for assigning biological or biochemical functions to a protein. They also lead to the identification of those significant proteins which are responsible for the generation of various diseases whose drugs are still yet to be discovered. So, the prediction of GO functional terms from PPIN and sequence is an important field of study. In this work, we have proposed a methodology, Multi Label Protein Function Prediction (ML_PFP) which is based on Neighborhood analysis empowered with physico-chemical features of constituent amino acids to predict the functional group of unannotated protein. A protein does not perform functions in isolation rather it performs functions in a group by interacting with others. So a protein is involved in many functions or, in other words, may be associated with multiple functional groups or labels or GO terms. Though functional group of other known interacting partner protein and its physico-chemical features provide useful information, assignment of multiple labels to unannotated protein is a very challenging task. Here, we have taken Homo sapiens or Human PPIN as well as Saccharomyces cerevisiae or yeast PPIN along with their GO terms to predict functional groups or GO terms of unannotated proteins. This work has become very challenging as both Human and Yeast protein dataset are voluminous and complex in nature and multi-label functional groups assignment has also added a new dimension to this challenge. Our algorithm has been observed to achieve a better performance in Cellular Function, Molecular Function and Biological Process of both yeast and human network when compared with the other existing state-of-the-art methodologies which will be discussed in detail in the results section.

DDTRP: Database of Drug Targets for Resistant Pathogens.

Emergence of drug resistance is a major threat to public health. Many pathogens have developed resistance to most of the existing antibiotics, and multidrug-resistant and extensively drug resistant strains are extremely difficult to treat. This has resulted in an urgent need for novel drugs. We describe a database called 'Database of Drug Targets for Resistant Pathogens' (DDTRP). The database contains information on drugs with reported resistance, their respective targets, metabolic pathways involving these targets, and a list of potential alternate targets for seven pathogens. The database can be accessed freely at http://bmi.icmr.org.in/DDTRP.