iTriplet, a rule-based nucleic acid sequence motif finder

<p>Abstract</p> <p>Background</p> <p>With the advent of high throughput sequencing techniques, large amounts of sequencing data are readily available for analysis. Natural biological signals are intrinsically highly variable making their complete identification a computationally challenging problem. Many attempts in using statistical or combinatorial approaches have been made with great success in the past. However, identifying highly degenerate and long (>20 nucleotides) motifs still remains an unmet challenge as high degeneracy will diminish statistical significance of biological signals and increasing motif size will cause combinatorial explosion. In this report, we present a novel rule-based method that is focused on finding degenerate and long motifs. Our proposed method, named iTriplet, avoids costly enumeration present in existing combinatorial methods and is amenable to parallel processing.</p> <p>Results</p> <p>We have conducted a comprehensive assessment on the performance and sensitivity-specificity of iTriplet in analyzing artificial and real biological sequences in various genomic regions. The results show that iTriplet is able to solve challenging cases. Furthermore we have confirmed the utility of iTriplet by showing it accurately predicts polyA-site-related motifs using a dual Luciferase reporter assay.</p> <p>Conclusion</p> <p>iTriplet is a novel rule-based combinatorial or enumerative motif finding method that is able to process highly degenerate and long motifs that have resisted analysis by other methods. In addition, iTriplet is distinguished from other methods of the same family by its parallelizability, which allows it to leverage the power of today's readily available high-performance computing systems.</p

Fast motif recognition via application of statistical thresholds

Background: Improving the accuracy and efficiency of motif recognition is an important computational challenge that has application to detecting transcription factor binding sites in genomic data. Closely related to motif recognition is the Consensus String decision problem that asks, given a parameter d and a set of ℓ-length strings S = {s1,...,sn}, whether there exists a consensus string that has Hamming distance at most d from any string in S. A set of strings S is pairwise bounded if the Hamming distance between any pair of strings in S is at most 2d. It is trivial to determine whether a set is pairwise bounded, and a set cannot have a consensus string unless it is pairwise bounded. We use Consensus String to determine whether or not a pairwise bounded set has a consensus. Unfortunately, Consensus String is NP-complete. The lack of an efficient method to solve the Consensus String problem has caused it to become a computational bottleneck in MCL-WMR, a motif recognition program capable of solving difficult motif recognition problem instances. Results: We focus on the development of a method for solving Consensus String quickly with a small probability of error. We apply this heuristic to develop a new motif recognition program, sMCL-WMR, which has impressive accuracy and efficiency. We demonstrate the performance of sMCL-WMR in detecting weak motifs in large data sets and in real genomic data sets, and compare the performance to other leading motif recognitio

High Performance Implementation of Planted Motif Problem using Suffix trees

In this paper we present a high performance implementation of suffix tree based solution to the planted motif problem on two different parallel architectures: NVIDIA GPU and Intel Multicore machines. An (l,d) planted motif problem(PMP) is defined as: Given a sequence of n DNA sequences, each of length L, find M, the set of sequences(or motifs) of length l which have atleast one d-neighbor in each of the n sequences. Here, a d-neighbor of a sequence is a sequence of same length that differs in at-most d positions. PMP is a well studied problem in computational biology. It is useful in developing methods for finding transcription factor binding sites, sequence classification and for building phylogenetic trees. The problem is computationally challenging to solve, for example a (19,7) PMP takes 9.9 hours on a sequential machine. Many approaches to solve planted motif problem can be found in literature. One approach is based on use of suffix tree data structure. Though suffix tree based methods are the most efficient ones for solving large planted motif problems on sequential machines, they are quite difficult to parallelize. We present suffix tree based parallel solutions for PMP on NVIDIA GPU and Intel Multicore architectures that are efficient and scalable. The solutions are based on a suffix tree algorithm previously presented but use extensive adaptation to individual architectures to ensure that the implementations work efficiently and scale well

Efficient motif finding algorithms for large-alphabet inputs

<p>Abstract</p> <p>Background</p> <p>We consider the problem of identifying motifs, recurring or conserved patterns, in the biological sequence data sets. To solve this task, we present a new deterministic algorithm for finding patterns that are embedded as exact or inexact instances in all or most of the input strings.</p> <p>Results</p> <p>The proposed algorithm (1) improves search efficiency compared to existing algorithms, and (2) scales well with the size of alphabet. On a synthetic planted DNA motif finding problem our algorithm is over 10× more efficient than MITRA, PMSPrune, and RISOTTO for long motifs. Improvements are orders of magnitude higher in the same setting with large alphabets. On benchmark TF-binding site problems (FNP, CRP, LexA) we observed reduction in running time of over 12×, with high detection accuracy. The algorithm was also successful in rapidly identifying protein motifs in Lipocalin, Zinc metallopeptidase, and supersecondary structure motifs for Cadherin and Immunoglobin families.</p> <p>Conclusions</p> <p>Our algorithm reduces computational complexity of the current motif finding algorithms and demonstrate strong running time improvements over existing exact algorithms, especially in important and difficult cases of large-alphabet sequences.</p

Parallel random projection using R high performance computing for planted motif search

Motif discovery in DNA sequences is one of the most important issues in bioinformatics. Thus, algorithms for dealing with the problem accurately and quickly have always been the goal of research in bioinformatics. Therefore, this study is intended to modify the random projection algorithm to be implemented on R high performance computing (i.e., the R package pbdMPI). Some steps are needed to achieve this objective, ie preprocessing data, splitting data according to number of batches, modifying and implementing random projection in the pbdMPI package, and then aggregating the results. To validate the proposed approach, some experiments have been conducted. Several benchmarking data were used in this study by sensitivity analysis on number of cores and batches. Experimental results show that computational cost can be reduced, which is that the computation cost of 6 cores is faster around 34 times compared with the standalone mode. Thus, the proposed approach can be used for motif discovery effectively and efficiently

Combinatorial and Probabilistic Approaches to Motif Recognition

Short substrings of genomic data that are responsible for biological processes, such as gene expression, are referred to as motifs. Motifs with the same function may not entirely match, due to mutation events at a few of the motif positions. Allowing for non-exact occurrences significantly complicates their discovery. Given a number of DNA strings, the motif recognition problem is the task of detecting motif instances in every given sequence without knowledge of the position of the instances or the pattern shared by these substrings. We describe a novel approach to motif recognition, and provide theoretical and experimental results that demonstrate its efficiency and accuracy. Our algorithm, MCL-WMR, builds an edge-weighted graph model of the given motif recognition problem and uses a graph clustering algorithm to quickly determine important subgraphs that need to be searched further for valid motifs. By considering a weighted graph model, we narrow the search dramatically to smaller problems that can be solved with significantly less computation. The Closest String problem is a subproblem of motif recognition, and it is NP-hard. We give a linear-time algorithm for a restricted version of the Closest String problem, and an efficient polynomial-time heuristic that solves the general problem with high probability. We initiate the study of the smoothed complexity of the Closest String problem, which in turn explains our empirical results that demonstrate the great capability of our probabilistic heuristic. Important to this analysis is the introduction of a perturbation model of the Closest String instances within which we provide a probabilistic analysis of our algorithm. The smoothed analysis suggests reasons why a well-known fixed parameter tractable algorithm solves Closest String instances extremely efficiently in practice. Although the Closest String model is robust to the oversampling of strings in the input, it is severely affected by the existence of outliers. We propose a refined model, the Closest String with Outliers problem, to overcome this limitation. A systematic parameterized complexity analysis accompanies the introduction of this problem, providing a surprising insight into the sensitivity of this problem to slightly different parameterizations. Through the application of probabilistic and combinatorial insights into the Closest String problem, we develop sMCL-WMR, a program that is much faster than its predecessor MCL-WMR. We apply and adapt sMCL-WMR and MCL-WMR to analyze the promoter regions of the canola seed-coat. Our results identify important regions of the canola genome that are responsible for specific biological activities. This knowledge may be used in the long-term aim of developing crop varieties with specific biological characteristics, such as being disease-resistant