Developing a Bioinformatics Pipeline to Assess the Potential Functional Impact of Novel Protein Isoforms

Abstract

While we know the sequence of the nucleotides that make up the DNA of the human genome, the process of annotating those nucleotides according to the transcripts that originate from them remains incomplete. Novel transcripts continue to be identified, and so methods must be devised to characterize these novel transcripts and prioritize them for future study by assessing potential hallmarks of function. One of the potential hallmarks of function is presence of an open reading frame with potential to produce a protein isoform that is not yet annotated. Based on the sequence of the novel protein isoform, an initial assessment of the potential functional impact of expression of the novel protein can be made: 1) Identification of the loss and/or gain of protein domains in the novel isoform versus the current annotated form of the protein. 2) Analysis of proteins that have lost and/or gained functional domains by generating 3D models of the annotated proteins and novel protein isoforms to facilitate potential understanding of functional impact. 3) Differential expression analysis of the putative exons at the RNA level to investigate disease-specificity of expression and potential changes in expression of the novel isoform in disease.