Efficient Algorithms for the Closest Pair Problem and Applications

The closest pair problem (CPP) is one of the well studied and fundamental problems in computing. Given a set of points in a metric space, the problem is to identify the pair of closest points. Another closely related problem is the fixed radius nearest neighbors problem (FRNNP). Given a set of points and a radius $R$, the problem is, for every input point $p$, to identify all the other input points that are within a distance of $R$ from $p$. A naive deterministic algorithm can solve these problems in quadratic time. CPP as well as FRNNP play a vital role in computational biology, computational finance, share market analysis, weather prediction, entomology, electro cardiograph, N-body simulations, molecular simulations, etc. As a result, any improvements made in solving CPP and FRNNP will have immediate implications for the solution of numerous problems in these domains. We live in an era of big data and processing these data take large amounts of time. Speeding up data processing algorithms is thus much more essential now than ever before. In this paper we present algorithms for CPP and FRNNP that improve (in theory and/or practice) the best-known algorithms reported in the literature for CPP and FRNNP. These algorithms also improve the best-known algorithms for related applications including time series motif mining and the two locus problem in Genome Wide Association Studies (GWAS)

Construction of minimal DFAs from biological motifs

Deterministic finite automata (DFAs) are constructed for various purposes in computational biology. Little attention, however, has been given to the efficient construction of minimal DFAs. In this article, we define simple non-deterministic finite automata (NFAs) and prove that the standard subset construction transforms NFAs of this type into minimal DFAs. Furthermore, we show how simple NFAs can be constructed from two types of patterns popular in bioinformatics, namely (sets of) generalized strings and (generalized) strings with a Hamming neighborhood

QuateXelero : an accelerated exact network motif detection algorithm

Finding motifs in biological, social, technological, and other types of networks has become a widespread method to gain more knowledge about these networks’ structure and function. However, this task is very computationally demanding, because it is highly associated with the graph isomorphism which is an NP problem (not known to belong to P or NP-complete subsets yet). Accordingly, this research is endeavoring to decrease the need to call NAUTY isomorphism detection method, which is the most time-consuming step in many existing algorithms. The work provides an extremely fast motif detection algorithm called QuateXelero, which has a Quaternary Tree data structure in the heart. The proposed algorithm is based on the well-known ESU (FANMOD) motif detection algorithm. The results of experiments on some standard model networks approve the overal superiority of the proposed algorithm, namely QuateXelero, compared with two of the fastest existing algorithms, G-Tries and Kavosh. QuateXelero is especially fastest in constructing the central data structure of the algorithm from scratch based on the input network

Transcription Factor-DNA Binding Via Machine Learning Ensembles

We present ensemble methods in a machine learning (ML) framework combining predictions from five known motif/binding site exploration algorithms. For a given TF the ensemble starts with position weight matrices (PWM's) for the motif, collected from the component algorithms. Using dimension reduction, we identify significant PWM-based subspaces for analysis. Within each subspace a machine classifier is built for identifying the TF's gene (promoter) targets (Problem 1). These PWM-based subspaces form an ML-based sequence analysis tool. Problem 2 (finding binding motifs) is solved by agglomerating k-mer (string) feature PWM-based subspaces that stand out in identifying gene targets. We approach Problem 3 (binding sites) with a novel machine learning approach that uses promoter string features and ML importance scores in a classification algorithm locating binding sites across the genome. For target gene identification this method improves performance (measured by the F1 score) by about 10 percentage points over the (a) motif scanning method and (b) the coexpression-based association method. Top motif outperformed 5 component algorithms as well as two other common algorithms (BEST and DEME). For identifying individual binding sites on a benchmark cross species database (Tompa et al., 2005) we match the best performer without much human intervention. It also improved the performance on mammalian TFs. The ensemble can integrate orthogonal information from different weak learners (potentially using entirely different types of features) into a machine learner that can perform consistently better for more TFs. The TF gene target identification component (problem 1 above) is useful in constructing a transcriptional regulatory network from known TF-target associations. The ensemble is easily extendable to include more tools as well as future PWM-based information.Comment: 33 page

Spectral Sequence Motif Discovery

Sequence discovery tools play a central role in several fields of computational biology. In the framework of Transcription Factor binding studies, motif finding algorithms of increasingly high performance are required to process the big datasets produced by new high-throughput sequencing technologies. Most existing algorithms are computationally demanding and often cannot support the large size of new experimental data. We present a new motif discovery algorithm that is built on a recent machine learning technique, referred to as Method of Moments. Based on spectral decompositions, this method is robust under model misspecification and is not prone to locally optimal solutions. We obtain an algorithm that is extremely fast and designed for the analysis of big sequencing data. In a few minutes, we can process datasets of hundreds of thousand sequences and extract motif profiles that match those computed by various state-of-the-art algorithms.Comment: 20 pages, 3 figures, 1 tabl