Algorithms for Gene Clustering Analysis on Genomes

The increased availability of data in biological databases provides many opportunities for understanding biological processes through these data. As recent attention has shifted from sequence analysis to higher-level analysis of genes across multiple genomes, there is a need to develop efficient algorithms for these large-scale applications that can help us understand the functions of genes. The overall objective of my research was to develop improved methods which can automatically assign groups of functionally related genes in large-scale data sets by applying new gene clustering algorithms. Proposed gene clustering algorithms that can help us understand gene function and genome evolution include new algorithms for protein family classification, a window-based strategy for gene clustering on chromosomes, and an exhaustive strategy that allows all clusters of small size to be enumerated. I investigate the problems of gene clustering in multiple genomes, and define gene clustering problems using mathematical methodology and solve the problems by developing efficient and effective algorithms. For protein family classification, I developed two supervised classification algorithms that can assign proteins to existing protein families in public databases and, by taking into account similarities between the unclassified proteins, allows for progressive construction of new families from proteins that cannot be assigned. This approach is useful for rapid assignment of protein sequences from genome sequencing projects to protein families. A comparative analysis of the method to other previously developed methods shows that the algorithm has a higher accuracy rate and lower mis-classification rate when compared to algorithms that are based on the use of multiple sequence alignments and hidden Markov models. The proposed algorithm performs well even on families with very few proteins and on families with low sequence similarity. Apart from the analysis of individual sequences, identifying genomic regions that descended from a common ancestor helps us study gene function and genome evolution. In distantly related genomes, clusters of homologous gene pairs serve as evidence used in function prediction, operon detection, etc. Thus, reliable identification of gene clusters is critical to functional annotation and analysis of genes. I developed an efficient gene clustering algorithm that can be applied on hundreds of genomes at the same time. This approach allows for large-scale study of evolutionary relationships of gene clusters and study of operon formation and destruction. By placing a stricter limit on the maximum cluster size, I developed another algorithm that uses a different formulation based on constraining the overall size of a cluster and statistical estimates that allow direct comparisons of clusters of different size. A comparative analysis of proposed algorithms shows that more biological insight can be obtained by analyzing gene clusters across hundreds of genomes, which can help us understand operon occurrences, gene orientations and gene rearrangements

TRAPID : an efficient online tool for the functional and comparative analysis of de novo RNA-Seq transcriptomes

Transcriptome analysis through next-generation sequencing technologies allows the generation of detailed gene catalogs for non-model species, at the cost of new challenges with regards to computational requirements and bioinformatics expertise. Here, we present TRAPID, an online tool for the fast and efficient processing of assembled RNA-Seq transcriptome data, developed to mitigate these challenges. TRAPID offers high-throughput open reading frame detection, frameshift correction and includes a functional, comparative and phylogenetic toolbox, making use of 175 reference proteomes. Benchmarking and comparison against state-of-the-art transcript analysis tools reveals the efficiency and unique features of the TRAPID system

Recovering complete and draft population genomes from metagenome datasets.

Assembly of metagenomic sequence data into microbial genomes is of fundamental value to improving our understanding of microbial ecology and metabolism by elucidating the functional potential of hard-to-culture microorganisms. Here, we provide a synthesis of available methods to bin metagenomic contigs into species-level groups and highlight how genetic diversity, sequencing depth, and coverage influence binning success. Despite the computational cost on application to deeply sequenced complex metagenomes (e.g., soil), covarying patterns of contig coverage across multiple datasets significantly improves the binning process. We also discuss and compare current genome validation methods and reveal how these methods tackle the problem of chimeric genome bins i.e., sequences from multiple species. Finally, we explore how population genome assembly can be used to uncover biogeographic trends and to characterize the effect of in situ functional constraints on the genome-wide evolution