Hongwei Huo

An efficient exact algorithm for the motif stem search problem over large alphabets

In recent years, there has been an increasing interest in planted (l, d) motif search (PMS) with applications to discovering significant segments in biological sequences. However, there has been little discussion about PMS over large alphabets. This paper focuses on motif stem search (MSS), which is recently introduced to search motifs on large-alphabet inputs. A motif stem is an l-length string with some wildcards. The goal of the MSS problem is to find a set of stems that represents a superset of all (l , d) motifs present in the input sequences, and the superset is expected to be as small as possible. The three main contributions of this paper are as follows: (1) We build motif stem representation more precisely by using regular expressions. (2) We give a method for generating all possible motif stems without redundant wildcards. (3) We propose an efficient exact algorithm, called StemFinder, for solving the MSS problem. Compared with the previous MSS algorithms, StemFinder runs much faster and reports fewer stems which represent a smaller superset of all (l, d) motifs. StemFinder is freely available at http://sites.google.com/site/feqond/stemfinder.

An Affinity Propagation-Based DNA Motif Discovery Algorithm

The planted (l, d) motif search (PMS) is one of the fundamental problems in bioinformatics, which plays an important role in locating transcription factor binding sites (TFBSs) in DNA sequences. Nowadays, identifying weak motifs and reducing the effect of local optimum are still important but challenging tasks for motif discovery. To solve the tasks, we propose a new algorithm, APMotif, which first applies the Affinity Propagation (AP) clustering in DNA sequences to produce informative and good candidate motifs and then employs Expectation Maximization (EM) refinement to obtain the optimal motifs from the candidate motifs. Experimental results both on simulated data sets and real biological data sets show that APMotif usually outperforms four other widely used algorithms in terms of high prediction accuracy.

A Practical Implementation of Compressed Suffix Arrays with Applications to Self-Indexing

In this paper we develop a simple and practical text indexing scheme for compressed suffix arrays (CSA). For a text of n characters, our CSA can be constructed in linear time and needs 2nHk + n + o(n) bits of space for any k ≤ clogσn - 1 and any constant c <; 1, where Hk denotes the kth order entropy. We compare the performance of our method with two established compressed indexing methods, the FM-index and the Sad-CSA. Experiments on the Canterbury Corpus and the Pizza&Chili Corpus show significant advantages of our algorithm over two other indexes in terms of compression and query time. Our storage scheme achieves better performance on all types of data present in these two corpora, except for evenly distributed data, such as DNA. The source code for our CSA is available online.

Reference sequence selection for motif searches

The planted (l, d) motif search (PMS) is an important yet challenging problem in computational biology. Pattern-driven PMS algorithms usually use k out of t input sequences as reference sequences to generate candidate motifs, and they can find all the (l, d) motifs in the input sequences. However, most of them simply take the first k sequences in the input as reference sequences without elaborate selection processes, and thus they may exhibit sharp fluctuations in running time, especially for large alphabets. In this paper, we build the reference sequence selection problem and propose a method named RefSelect to quickly solve it by evaluating the number of candidate motifs for the reference sequences. RefSelect can bring a practical time improvement of the state-of-the-art pattern-driven PMS algorithms. Experimental results show that RefSelect (1) makes the tested algorithms solve the PMS problem steadily in an efficient way, (2) particularly, makes them achieve a speedup of up to about 100× on the protein data, and (3) is also suitable for large data sets which contain hundreds or more sequences.

An efficient motif finding algorithm for large DNA data sets

The planted (l, d) motif discovery has been successfully used to locate transcription factor binding sites in dozens of promoter sequences over the past decade. However, there has not been enough work done in identifying (l, d) motifs in the next-generation sequencing (ChIP-seq) data sets, which contain thousands of input sequences and thereby bring new challenge to make a good identification in reasonable time. To cater this need, we propose a new planted (l, d) motif discovery algorithm named MCES, which identifies motifs by mining and combining emerging substrings. Specially, to handle larger data sets, we design a MapReduce-based strategy to mine emerging substrings distributedly. Experimental results on the simulated data show that i) MCES is able to identify (l, d) motifs efficiently and effectively in thousands to millions of input sequences, and runs faster than the state-of-the-art (l, d) motif discovery algorithms, such as F-motif and TraverStringsR; ii) MCES is able to identify motifs without known lengths, and has a better identification accuracy than the competing algorithm CisFinder. Also, the validity of MCES is tested on real data sets.

StemFinder: An efficient algorithm for searching motif stems over large alphabets

Motif stem search (MSS) is a recent motif search problem to search motifs on large-alphabet inputs. A motif stem is an l-length string with some wildcards. The goal of the MSS problem is to find a set of stems that represents a superset of all (l, d) motifs present in the input sequences. The three main contributions of this paper are as follows: (1) We build motif stem representation more precisely by using regular expressions. (2) We give a new method for generating all possible motif stems. (3) We propose an efficient algorithm, called StemFinder, for solving the MSS problem. Compared with the previous algorithms, StemFinder runs much faster and first solves the (17, 8), (19, 9) and (21, 10) challenging instances on protein sequences; moreover, StemFinder reports fewer stems representing a smaller superset of all (l, d) motifs.

PairMotifChIP: A Fast Algorithm for Discovery of Patterns Conserved in Large ChIP-seq Data Sets

Identifying conserved patterns in DNA sequences, namely, motif discovery, is an important and challenging computational task. With hundreds or more sequences contained, the high-throughput sequencing data set is helpful to improve the identification accuracy of motif discovery but requires an even higher computing performance. To efficiently identify motifs in large DNA data sets, a new algorithm called PairMotifChIP is proposed by extracting and combining pairs of l-mers in the input with relatively small Hamming distance. In particular, a method for rapidly extracting pairs of l-mers is designed, which can be used not only for PairMotifChIP, but also for other DNA data mining tasks with the same demand. Experimental results on the simulated data show that the proposed algorithm can find motifs successfully and runs faster than the state-of-the-art motif discovery algorithms. Furthermore, the validity of the proposed algorithm has been verified on real data.

An Efficient Algorithm for Discovering Motifs in Large DNA Data Sets

The planted (l,d) motif discovery has been successfully used to locate transcription factor binding sites in dozens of promoter sequences over the past decade. However, there has not been enough work done in identifying (l,d) motifs in the next-generation sequencing (ChIP-seq) data sets, which contain thousands of input sequences and thereby bring new challenge to make a good identification in reasonable time. To cater this need, we propose a new planted (l,d) motif discovery algorithm named MCES, which identifies motifs by mining and combining emerging substrings. Specially, to handle larger data sets, we design a MapReduce-based strategy to mine emerging substrings distributedly. Experimental results on the simulated data show that i) MCES is able to identify (l,d) motifs efficiently and effectively in thousands to millions of input sequences, and runs faster than the state-of-the-art (l,d) motif discovery algorithms, such as F-motif and TraverStringsR; ii) MCES is able to identify motifs without known lengths, and has a better identification accuracy than the competing algorithm CisFinder. Also, the validity of MCES is tested on real data sets. MCES is freely available at http://sites.google.com/site/feqond/mces.

CS2A: A Compressed Suffix Array-Based Method for Short Read Alignment

Next generation sequencing technologies generate normous amount of short reads, which poses a significant computational challenge for short read alignment. Furthermore, because of sequence polymorphisms in a population, repetitive sequences, and sequencing errors, there still exist difficulties in correctly aligning all reads. We propose a space-efficient compressed suffix array-based method for short read alignment (CS2A) whose space achieves the high-order empirical entropy of the input string. Unlike BWA that uses two bits to represent a nucleotide, suitable for constant-sized alphabets, our encoding scheme can be applied to the string with any alphabet set. In addition, we present approximate pattern matching on compressed suffix array (CSA) for short read alignment. Our CS2A supports both mismatch and gapped alignments for single-end and paired-end reads mapping, being capable of efficiently aligning short sequencing reads to genome sequences. The experimental results show that CS2A can compete with the popular aligners in memory usage and mapping accuracy. The source code is available online.

RefSelect: a reference sequence selection algorithm for planted (l, d) motif search

BackgroundThe planted (l, d) motif search (PMS) is an important yet challenging problem in computational biology. Pattern-driven PMS algorithms usually use k out of t input sequences as reference sequences to generate candidate motifs, and they can find all the (l, d) motifs in the input sequences. However, most of them simply take the first k sequences in the input as reference sequences without elaborate selection processes, and thus they may exhibit sharp fluctuations in running time, especially for large alphabets.ResultsIn this paper, we build the reference sequence selection problem and propose a method named RefSelect to quickly solve it by evaluating the number of candidate motifs for the reference sequences. RefSelect can bring a practical time improvement of the state-of-the-art pattern-driven PMS algorithms. Experimental results show that RefSelect (1) makes the tested algorithms solve the PMS problem steadily in an efficient way, (2) particularly, makes them achieve a speedup of up to about 100× on the protein data, and (3) is also suitable for large data sets which contain hundreds or more sequences.ConclusionsThe proposed algorithm RefSelect can be used to solve the problem that many pattern-driven PMS algorithms present execution time instability. RefSelect requires a small amount of storage space and is capable of selecting reference sequences efficiently and effectively. Also, the parallel version of RefSelect is provided for handling large data sets.