Bioinformatics Methods for Diagnosis and Treatment of Human Diseases

Date of Completion

January 2010


Biology, Bioinformatics|Computer Science




The availability of large databases of genomic information has enabled research efforts focused on refining methods for diagnosis and treatment of human diseases. However, proper use of genomic databases can not be achieved without the development of sophisticated data analysis methods, which is by itself a challenging task due to the size and heterogeneity of the data. The focus of the research proposed in this document is on developing computational methods and software tools for diagnosis and treatment of human diseases. ^ We describe a primers design tool for rapid virus subtype identification, applied to Avian Influenza called PrimerHunter, which takes as input sets of both target and non-target sequences and select primers that efficiently amplify any one of the targets, and none of the non-targets. PrimerHunter ensures the desired amplification properties by using accurate estimates of melting temperature with mismatches, computed based on the nearest-neighbor model via an efficient fractional programming algorithm.^ We also present a bioinformatics pipeline for detection of immunogenic cancer mutations by high throughput mRNA sequencing. As part of this pipeline, we developed and integrated novel algorithms and strategies for mRNA reads mapping, SNV detection, genotyping and haplotyping. We show through validations on real data that our methods improve accuracy to identify expressed mutations over existing methods and that our haplotyping algorithm is more efficient than other solutions with comparable accuracy levels. Our pipeline predicted more than a thousand candidate epitopes for six different mouse cancer tumor cell lines, which are currently used to find stable protocols for immunotherapy. ^