Mapping and Filling Metabolic Pathway Holes

The network-mapping tool integrated with protein database search can be used for filling pathway holes. A metabolic pathway under consideration (pattern) is mapped into a known metabolic pathway (text), to find pathway holes. Enzymes that do not show up in the pattern may be a hole in the pattern pathway or an indication of alternative pattern pathway. We present a data-mining framework for filling holes in the pattern metabolic pathway based on protein function, prosite scan and protein sequence homology. Using this framework we suggest several fillings found with the same EC notation, with group neighbors (enzymes with same EC number in first three positions, different in the fourth position), and instances where the function of an enzyme has been taken up by the left or right neighboring enzyme in the pathway. The percentile scores are better when closely related organisms are mapped as compared to mapping distantly related organisms

Metabolic Network Alignments and their Applications

The accumulation of high-throughput genomic and proteomic data allows for the reconstruction of the increasingly large and complex metabolic networks. In order to analyze the accumulated data and reconstructed networks, it is critical to identify network patterns and evolutionary relations between metabolic networks. But even finding similar networks becomes computationally challenging. The dissertation addresses these challenges with discrete optimization and the corresponding algorithmic techniques. Based on the property of the gene duplication and function sharing in biological network,we have formulated the network alignment problem which asks the optimal vertex-to-vertex mapping allowing path contraction, vertex deletion, and vertex insertions. We have proposed the first polynomial time algorithm for aligning an acyclic metabolic pattern pathway with an arbitrary metabolic network. We also have proposed a polynomial-time algorithm for patterns with small treewidth and implemented it for series-parallel patterns which are commonly found among metabolic networks. We have developed the metabolic network alignment tool for free public use. We have performed pairwise mapping of all pathways among five organisms and found a set of statistically significant pathway similarities. We also have applied the network alignment to identifying inconsistency, inferring missing enzymes, and finding potential candidates

Homomorphisms of Multisource Trees into Networks with Applications to Metabolic Pathways

Network mapping is a convenient tool for comparing and exploring biological networks; it can be used for predicting unknown pathways, fast and meaningful searching of databases, and potentially establishing evolutionary relations. Unfortunately, existing tools for mapping paths into general networks (PathBlast) or trees into tree networks allowing gaps (MetaPathwayHunter) cannot handle large query pathways or complex networks. In this paper we consider homomorphisms, i.e., mappings allowing to map different enzymes from the query pathway into the same enzyme from the networks. Homomorphisms are more general than homeomorphism (allowing gaps) and easier to handle algorithmically. Our dynamic programming algorithm efficiently finds the minimum cost homomorphism from a multisource tree to directed acyclic graphs as well as general networks. We have performed pairwise mapping of all pathways for four organisms (E. coli, S. cerevisiae, B. subtilis and T. thermophilus species) and found a reasonably large set of statistically significant pathway similarities. Further analysis of our mappings identifies conserved pathways across examined species and indicates potential pathway holes in existing pathway descriptions. Availability: The software is available from the authors on request

2008-2009-UNM CATALOG

Course catalog for 2008-2009https://digitalrepository.unm.edu/course_catalogs/1098/thumbnail.jp

2009-2010 UNM Catalog

Course catalog for the years 2009-2010.https://digitalrepository.unm.edu/course_catalogs/1099/thumbnail.jp