T-Gene: improved target gene prediction.

Motivation: Identifying the genes regulated by a given transcription factor (TF) (its 'target genes') is a key step in developing a comprehensive understanding of gene regulation. Previously, we developed a method (CisMapper) for predicting the target genes of a TF based solely on the correlation between a histone modification at the TF's binding site and the expression of the gene across a set of tissues or cell lines. That approach is limited to organisms for which extensive histone and expression data are available, and does not explicitly incorporate the genomic distance between the TF and the gene.

MoMo: discovery of statistically significant post-translational modification motifs.

Motivation: Post-translational modifications (PTMs) of proteins are associated with many significant biological functions and can be identified in high throughput using tandem mass spectrometry. Many PTMs are associated with short sequence patterns called 'motifs' that help localize the modifying enzyme. Accordingly, many algorithms have been designed to identify these motifs from mass spectrometry data.

Little evidence for intralocus sexual conflict over the optimal intake of nutrients for life span and reproduction in the black field cricket Teleogryllus commodus.

There is often large divergence in the effects of key nutrients on life span (LS) and reproduction in the sexes, yet nutrient intake is regulated in the same way in males and females given dietary choice. This suggests that the sexes are constrained from feeding to their sex-specific nutritional optima for these traits. Here, we examine the potential for intralocus sexual conflict (IASC) over optimal protein and carbohydrate intake for LS and reproduction to constrain the evolution of sex-specific nutrient regulation in the field cricket, Teleogryllus commodus.

MCAST: scanning for cis-regulatory motif clusters.

Unlabelled: Precise regulatory control of genes, particularly in eukaryotes, frequently requires the joint action of multiple sequence-specific transcription factors. A cis-regulatory module (CRM) is a genomic locus that is responsible for gene regulation and that contains multiple transcription factor binding sites in close proximity. Given a collection of known transcription factor binding motifs, many bioinformatics methods have been proposed over the past 15 years for identifying within a genomic sequence candidate CRMs consisting of clusters of those motifs.

The MEME Suite.

The MEME Suite is a powerful, integrated set of web-based tools for studying sequence motifs in proteins, DNA and RNA. Such motifs encode many biological functions, and their detection and characterization is important in the study of molecular interactions in the cell, including the regulation of gene expression. Since the previous description of the MEME Suite in the 2009 Nucleic Acids Research Web Server Issue, we have added six new tools.

Crux: rapid open source protein tandem mass spectrometry analysis.

Efficiently and accurately analyzing big protein tandem mass spectrometry data sets requires robust software that incorporates state-of-the-art computational, machine learning, and statistical methods. The Crux mass spectrometry analysis software toolkit ( http://cruxtoolkit.sourceforge.

Improved similarity scores for comparing motifs.

Motivation: A question that often comes up after applying a motif finder to a set of co-regulated DNA sequences is whether the reported putative motif is similar to any known motif. While several tools have been designed for this task, Habib et al. pointed out that the scores that are commonly used for measuring similarity between motifs do not distinguish between a good alignment of two informative columns (say, all-A) and one of two uninformative columns.

FIMO: scanning for occurrences of a given motif.

Unlabelled: A motif is a short DNA or protein sequence that contributes to the biological function of the sequence in which it resides. Over the past several decades, many computational methods have been described for identifying, characterizing and searching with sequence motifs. Critical to nearly any motif-based sequence analysis pipeline is the ability to scan a sequence database for occurrences of a given motif described by a position-specific frequency matrix.

MEME SUITE: tools for motif discovery and searching.

The MEME Suite web server provides a unified portal for online discovery and analysis of sequence motifs representing features such as DNA binding sites and protein interaction domains. The popular MEME motif discovery algorithm is now complemented by the GLAM2 algorithm which allows discovery of motifs containing gaps. Three sequence scanning algorithms--MAST, FIMO and GLAM2SCAN--allow scanning numerous DNA and protein sequence databases for motifs discovered by MEME and GLAM2.

Widely distributed noncoding purifying selection in the human genome.

It is widely assumed that human noncoding sequences comprise a substantial reservoir for functional variants impacting gene regulation and other chromosomal processes. Evolutionarily conserved noncoding sequences (CNSs) in the human genome have attracted considerable attention for their potential to simplify the search for functional elements and phenotypically important human alleles. A major outstanding question is whether functionally significant human noncoding variation is concentrated in CNSs or distributed more broadly across the genome.