Where Does the Alignment Score Distribution Shape Come from?

Alignment algorithms are powerful tools for searching for homologous proteins in databases, providing a score for each sequence present in the database. It has been well known for 20 years that the shape of the score distribution looks like an extreme value distribution. The extremely large number of times biologists face this class of distributions raises the question of the evolutionary origin of this probability law

Quantitative analysis by renormalized entropy of invasive electroencephalograph recordings in focal epilepsy

Invasive electroencephalograph (EEG) recordings of ten patients suffering from focal epilepsy were analyzed using the method of renormalized entropy. Introduced as a complexity measure for the different regimes of a dynamical system, the feature was tested here for its spatio-temporal behavior in epileptic seizures. In all patients a decrease of renormalized entropy within the ictal phase of seizure was found. Furthermore, the strength of this decrease is monotonically related to the distance of the recording location to the focus. The results suggest that the method of renormalized entropy is a useful procedure for clinical applications like seizure detection and localization of epileptic foci.Comment: 10 pages, 5 figure

The Transporter Classification Database: recent advances

The Transporter Classification Database (TCDB), freely accessible at http://www.tcdb.org, is a relational database containing sequence, structural, functional and evolutionary information about transport systems from a variety of living organisms, based on the International Union of Biochemistry and Molecular Biology-approved transporter classification (TC) system. It is a curated repository for factual information compiled largely from published references. It uses a functional/phylogenetic system of classification, and currently encompasses about 5000 representative transporters and putative transporters in more than 500 families. We here describe novel software designed to support and extend the usefulness of TCDB. Our recent efforts render it more user friendly, incorporate machine learning to input novel data in a semiautomatic fashion, and allow analyses that are more accurate and less time consuming. The availability of these tools has resulted in recognition of distant phylogenetic relationships and tremendous expansion of the information available to TCDB users

Application of the Multi-modal Relevance Vector Machine to the Problem of Protein Secondary Structure Prediction

The aim of the paper is to experimentally examine the plausibility of Relevance Vector Machines (RVM) for protein secondary structure prediction. We restrict our attention to detecting strands which represent an especially problematic element of the secondary structure. The commonly adopted local principle of secondary structure prediction is applied, which implies comparison of a sliding window in the given polypeptide chain with a number of reference amino-acid sequences cut out of the training proteins as benchmarks representing the classes of secondary structure. As distinct from the classical RVM, the novel version applied in this paper allows for selective combination of several tentative window comparison modalities. Experiments on the RS126 data set have shown its ability to essentially decrease the number of reference fragments in the resulting decision rule and to select a subset of the most appropriate comparison modalities within the given set of the tentative ones. © 2012 Springer-Verlag

Scaling properties of protein family phylogenies

One of the classical questions in evolutionary biology is how evolutionary processes are coupled at the gene and species level. With this motivation, we compare the topological properties (mainly the depth scaling, as a characterization of balance) of a large set of protein phylogenies with a set of species phylogenies. The comparative analysis shows that both sets of phylogenies share remarkably similar scaling behavior, suggesting the universality of branching rules and of the evolutionary processes that drive biological diversification from gene to species level. In order to explain such generality, we propose a simple model which allows us to estimate the proportion of evolvability/robustness needed to approximate the scaling behavior observed in the phylogenies, highlighting the relevance of the robustness of a biological system (species or protein) in the scaling properties of the phylogenetic trees. Thus, the rules that govern the incapability of a biological system to diversify are equally relevant both at the gene and at the species level.Comment: Replaced with final published versio

Non-Negative Matrix Factorization for Learning Alignment-Specific Models of Protein Evolution

Models of protein evolution currently come in two flavors: generalist and specialist. Generalist models (e.g. PAM, JTT, WAG) adopt a one-size-fits-all approach, where a single model is estimated from a number of different protein alignments. Specialist models (e.g. mtREV, rtREV, HIVbetween) can be estimated when a large quantity of data are available for a single organism or gene, and are intended for use on that organism or gene only. Unsurprisingly, specialist models outperform generalist models, but in most instances there simply are not enough data available to estimate them. We propose a method for estimating alignment-specific models of protein evolution in which the complexity of the model is adapted to suit the richness of the data. Our method uses non-negative matrix factorization (NNMF) to learn a set of basis matrices from a general dataset containing a large number of alignments of different proteins, thus capturing the dimensions of important variation. It then learns a set of weights that are specific to the organism or gene of interest and for which only a smaller dataset is available. Thus the alignment-specific model is obtained as a weighted sum of the basis matrices. Having been constrained to vary along only as many dimensions as the data justify, the model has far fewer parameters than would be required to estimate a specialist model. We show that our NNMF procedure produces models that outperform existing methods on all but one of 50 test alignments. The basis matrices we obtain confirm the expectation that amino acid properties tend to be conserved, and allow us to quantify, on specific alignments, how the strength of conservation varies across different properties. We also apply our new models to phylogeny inference and show that the resulting phylogenies are different from, and have improved likelihood over, those inferred under standard models

Biological Sequence Simulation for Testing Complex Evolutionary Hypotheses: indel-Seq-Gen Version 2.0

Sequence simulation is an important tool in validating biological hypotheses as well as testing various bioinformatics and molecular evolutionary methods. Hypothesis testing relies on the representational ability of the sequence simulation method. Simple hypotheses are testable through simulation of random, homogeneously evolving sequence sets. However, testing complex hypotheses, for example, local similarities, requires simulation of sequence evolution under heterogeneous models. To this end, we previously introduced indel-Seq-Gen version 1.0 (iSGv1.0; indel, insertion/deletion). iSGv1.0 allowed heterogeneous protein evolution and motif conservation as well as insertion and deletion constraints in subsequences. Despite these advances, for complex hypothesis testing, neither iSGv1.0 nor other currently available sequence simulation methods is sufficient. indel-Seq-Gen version 2.0 (iSGv2.0) aims at simulating evolution of highly divergent DNA sequences and protein superfamilies. iSGv2.0 improves upon iSGv1.0 through the addition of lineage-specific evolution, motif conservation using PROSITE-like regular expressions, indel tracking, subsequence-length constraints, as well as coding and noncoding DNA evolution. Furthermore, we formalize the sequence representation used for iSGv2.0 and uncover a flaw in the modeling of indels used in current state of the art methods, which biases simulation results for hypotheses involving indels. We fix this flaw in iSGv2.0 by using a novel discrete stepping procedure. Finally, we present an example simulation of the calycin-superfamily sequences and compare the performance of iSGv2.0 with iSGv1.0 and random model of sequence evolution