Fast motif matching revisited: high-order PWMs, SNPs and indels.

Motivation: While the position weight matrix (PWM) is the most popular model for sequence motifs, there is growing evidence of the usefulness of more advanced models such as first-order Markov representations, and such models are also becoming available in well-known motif databases. There has been lots of research of how to learn these models from training data but the problem of predicting putative sites of the learned motifs by matching the model against new sequences has been given less attention. Moreover, motif site analysis is often concerned about how different variants in the sequence affect the sites. So far, though, the corresponding efficient software tools for motif matching have been lacking. Results: We develop fast motif matching algorithms for the aforementioned tasks. First, we formalize a framework based on high-order position weight matrices for generic representation of motif models with dinucleotide or general q -mer dependencies, and adapt fast PWM matching algorithms to the high-order PWM framework. Second, we show how to incorporate different types of sequence variants , such as SNPs and indels, and their combined effects into efficient PWM matching workflows. Benchmark results show that our algorithms perform well in practice on genome-sized sequence sets and are for multiple motif search much faster than the basic sliding window algorithm. Availability and Implementation: Implementations are available as a part of the MOODS software package under the GNU General Public License v3.0 and the Biopython license ( http://www.cs.helsinki.fi/group/pssmfind ). Contact: janne.h.korhonen@gmail.com.

Separating OR, SUM, and XOR Circuits.

Given a boolean n × n matrix A we consider arithmetic circuits for computing the transformation x ↦ Ax over different semirings. Namely, we study three circuit models: monotone OR-circuits, monotone SUM-circuits (addition of non-negative integers), and non-monotone XOR-circuits (addition modulo 2). Our focus is on separating OR-circuits from the two other models in terms of circuit complexity: We show how to obtain matrices that admit OR-circuits of size O(n), but require SUM-circuits of size Ω(n3/2/log2n).We consider the task of rewriting a given OR-circuit as a XOR-circuit and prove that any subquadratic-time algorithm for this task violates the strong exponential time hypothesis.