Kun-Mao Chao

A polynomial time approximation scheme for minimum routing cost spanning trees

Given an undirected graph with nonnegative costs on the edges, the routing cost of any of its spanning trees is the sum over all pairs of vertices of the cost of the path between the pair in the tree. Finding a spanning tree of minimum routing cost is NP-hard, even when the costs obey the triangle inequality. We show that the general case is in fact reducible to the metric case and present a polynomial-time approximation scheme valid for both versions of the problem. In particular, we show how to build a spanning tree of an n-vertex weighted graph with routing cost at most

Aligning two sequences within a specified diagonal band

(1+\epsilon)

Efficient algorithms for locating the length-constrained heaviest segments with applications to biomolecular sequence analysis

of the minimum in time

A generalized global alignment algorithm

O(n^{O({\frac{1}{\epsilon}}% )})

PhosphoPOINT: a comprehensive human kinase interactome and phospho-protein database

. Besides the obvious connection to network design, trees with small routing cost also find application in the construction of good multiple sequence alignments in computational biology. The communication cost spanning tree problem is a generalization of the minimum routing cost tree problem where the routing costs of different pairs are weighted by different requirement amounts. We observe that a randomized O(log n log log n)-approximation for this problem follows directly from a recent result of Bartal, where n is the number of nodes in a metric graph. This also yields the same approximation for the generalized sum-of-pairs alignment problem in computational biology.

Pulmonary Tuberculosis and Delay in Anti-Tuberculous Treatment Are Important Risk Factors for Chronic Obstructive Pulmonary Disease

We describe an algorithm for aligning two sequences within a diagonal band that requires only O(NW) computation time and O(N) space, where N is the length of the shorter of the two sequences and W is the width of the band. The basic algorithm can be used to calculate either local or global alignment scores. Local alignments are produced by finding the beginning and end of a best local alignment in the band, and then applying the global alignment algorithm between those points. This algorithm has been incorporated into the FASTA program package, where it has decreased the amount of memory required to calculate local alignments from O(NW) to O(N) and decreased the time required to calculate optimized scores for every sequence in a protein sequence database by 40%. On computers with limited memory, such as the IBM-PC, this improvement both allows longer sequences to be aligned and allows optimization within wider bands, which can include longer gaps.

An approximation algorithm for haplotype inference by maximum parsimony.

We study two fundamental problems concerning the search for interesting regions in sequences: (i) given a sequence of real numbers of length n and an upper bound U, find a consecutive subsequence of length at most U with the maximum sum and (ii) given a sequence of real numbers of length n and a lower bound L, find a consecutive subsequence of length at least L with the maximum average. We present an O(n)-time algorithm for the first problem and an O(n log L)-time algorithm for the second. The algorithms have potential applications in several areas of biomolecular sequence analysis including locating GC-rich regions in a genomic DNA sequence, post-processing sequence alignments, annotating multiple sequence alignments, and computing length-constrained ungapped local alignment. Our preliminary tests on both simulated and real data demonstrate that the algorithms are very efficient and able to locate useful (such as GC-rich) regions.

Approximation algorithms for some optimum communication spanning tree problems

MOTIVATION Homologous sequences are sometimes similar over some regions but different over other regions. Homologous sequences have a much lower global similarity if the different regions are much longer than the similar regions. RESULTS We present a generalized global alignment algorithm for comparing sequences with intermittent similarities, an ordered list of similar regions separated by different regions. A generalized global alignment model is defined to handle sequences with intermittent similarities. A dynamic programming algorithm is designed to compute an optimal general alignment in time proportional to the product of sequence lengths and in space proportional to the sum of sequence lengths. The algorithm is implemented as a computer program named GAP3 (Global Alignment Program Version 3). The generalized global alignment model is validated by experimental results produced with GAP3 on both DNA and protein sequences. The GAP3 program extends the ability of standard global alignment programs to recognize homologous sequences of lower similarity. AVAILABILITY The GAP3 program is freely available for academic use at http://bioinformatics.iastate.edu/aat/align/align.html.

On the generalized constrained longest common subsequence problems

MOTIVATION To fully understand how a protein kinase regulates biological processes, it is imperative to first identify its substrate(s) and interacting protein(s). However, of the 518 known human serine/threonine/tyrosine kinases, 35% of these have known substrates, while 14% of the kinases have identified substrate recognition motifs. In contrast, 85% of the kinases have protein-protein interaction (PPI) datasets, raising the possibility that we might reveal potential kinase-substrate pairs from these PPIs. RESULTS PhosphoPOINT, a comprehensive human kinase interactome and phospho-protein database, is a collection of 4195 phospho-proteins with a total of 15 738 phosphorylation sites. PhosphoPOINT annotates the interactions among kinases, with their down-stream substrates and with interacting (phospho)-proteins to modulate the kinase-substrate pairs. PhosphoPOINT implements various gene expression profiles and Gene Ontology cellular component information to evaluate each kinase and their interacting (phospho)-proteins/substrates. Integration of cSNPs that cause amino acids change with the proteins with the phosphoprotein dataset reveals that 64 phosphorylation sites result in a disease phenotypes when changed; the linked phenotypes include schizophrenia and hypertension. PhosphoPOINT also provides a search function for all phospho-peptides using about 300 known kinase/phosphatase substrate/binding motifs. Altogether, PhosphoPOINT provides robust annotation for kinases, their downstream substrates and their interaction (phospho)-proteins and this should accelerate the functional characterization of kinomemediated signaling. AVAILABILITY PhosphoPOINT can be freely accessed in http://kinase. bioinformatics.tw/. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

MAVG: locating non-overlapping maximum average segments in a given sequence

Objective Tuberculosis (TB) remains the leading cause of death among infectious diseases worldwide. It has been suggested as an important risk factor of chronic obstructive pulmonary disease (COPD), which is also a major cause of morbidity and mortality. This study investigated the impact of pulmonary TB and anti-TB treatment on the risk of developing COPD. Design, Setting, and Participants This cohort study used the National Health Insurance Database of Taiwan, particularly the Longitudinal Health Insurance Database 2005 to obtain 3,176 pulmonary TB cases and 15,880 control subjects matched in age, sex, and timing of entering the database. Main Outcome Measures Hazard ratios of potential risk factors of COPD, especially pulmonary TB and anti-TB treatment. Results The mean age of pulmonary TB cases was 51.9±19.2. The interval between the initial study date and commencement of anti-TB treatment (delay in anti-TB treatment) was 75.8±65.4 days. Independent risk factors for developing COPD were age, male, low income, and history of pulmonary TB (hazard ratio 2.054 [1.768–2.387]), while diabetes mellitus was protective. The impact of TB persisted for six years after TB diagnosis and was significant in women and subjects aged >70 years. Among TB patients, delay in anti-TB treatment had a dose-response relationship with the risk of developing COPD. Conclusions Some cases of COPD may be preventable by controlling the TB epidemic, early TB diagnosis, and prompt initiation of appropriate anti-TB treatment. Follow-up care and early intervention for COPD may be necessary for treated TB patients.