Developing and applying heterogeneous phylogenetic models with XRate

Modeling sequence evolution on phylogenetic trees is a useful technique in computational biology. Especially powerful are models which take account of the heterogeneous nature of sequence evolution according to the "grammar" of the encoded gene features. However, beyond a modest level of model complexity, manual coding of models becomes prohibitively labor-intensive. We demonstrate, via a set of case studies, the new built-in model-prototyping capabilities of XRate (macros and Scheme extensions). These features allow rapid implementation of phylogenetic models which would have previously been far more labor-intensive. XRate's new capabilities for lineage-specific models, ancestral sequence reconstruction, and improved annotation output are also discussed. XRate's flexible model-specification capabilities and computational efficiency make it well-suited to developing and prototyping phylogenetic grammar models. XRate is available as part of the DART software package: http://biowiki.org/DART .Comment: 34 pages, 3 figures, glossary of XRate model terminolog

Computational identification and analysis of noncoding RNAs - Unearthing the buried treasures in the genome

The central dogma of molecular biology states that the genetic information flows from DNA to RNA to protein. This dogma has exerted a substantial influence on our understanding of the genetic activities in the cells. Under this influence, the prevailing assumption until the recent past was that genes are basically repositories for protein coding information, and proteins are responsible for most of the important biological functions in all cells. In the meanwhile, the importance of RNAs has remained rather obscure, and RNA was mainly viewed as a passive intermediary that bridges the gap between DNA and protein. Except for classic examples such as tRNAs (transfer RNAs) and rRNAs (ribosomal RNAs), functional noncoding RNAs were considered to be rare. However, this view has experienced a dramatic change during the last decade, as systematic screening of various genomes identified myriads of noncoding RNAs (ncRNAs), which are RNA molecules that function without being translated into proteins [11], [40]. It has been realized that many ncRNAs play important roles in various biological processes. As RNAs can interact with other RNAs and DNAs in a sequence-specific manner, they are especially useful in tasks that require highly specific nucleotide recognition [11]. Good examples are the miRNAs (microRNAs) that regulate gene expression by targeting mRNAs (messenger RNAs) [4], [20], and the siRNAs (small interfering RNAs) that take part in the RNAi (RNA interference) pathways for gene silencing [29], [30]. Recent developments show that ncRNAs are extensively involved in many gene regulatory mechanisms [14], [17]. The roles of ncRNAs known to this day are truly diverse. These include transcription and translation control, chromosome replication, RNA processing and modification, and protein degradation and translocation [40], just to name a few. These days, it is even claimed that ncRNAs dominate the genomic output of the higher organisms such as mammals, and it is being suggested that the greater portion of their genome (which does not encode proteins) is dedicated to the control and regulation of cell development [27]. As more and more evidence piles up, greater attention is paid to ncRNAs, which have been neglected for a long time. Researchers began to realize that the vast majority of the genome that was regarded as “junk,” mainly because it was not well understood, may indeed hold the key for the best kept secrets in life, such as the mechanism of alternative splicing, the control of epigenetic variations and so forth [27]. The complete range and extent of the role of ncRNAs are not so obvious at this point, but it is certain that a comprehensive understanding of cellular processes is not possible without understanding the functions of ncRNAs [47]

Robust Spoken Language Understanding for House Service Robots

Service robotics has been growing significantly in thelast years, leading to several research results and to a numberof consumer products. One of the essential features of theserobotic platforms is represented by the ability of interactingwith users through natural language. Spoken commands canbe processed by a Spoken Language Understanding chain, inorder to obtain the desired behavior of the robot. The entrypoint of such a process is represented by an Automatic SpeechRecognition (ASR) module, that provides a list of transcriptionsfor a given spoken utterance. Although several well-performingASR engines are available off-the-shelf, they operate in a generalpurpose setting. Hence, they may be not well suited in therecognition of utterances given to robots in specific domains. Inthis work, we propose a practical yet robust strategy to re-ranklists of transcriptions. This approach improves the quality of ASRsystems in situated scenarios, i.e., the transcription of roboticcommands. The proposed method relies upon evidences derivedby a semantic grammar with semantic actions, designed tomodel typical commands expressed in scenarios that are specificto human service robotics. The outcomes obtained throughan experimental evaluation show that the approach is able toeffectively outperform the ASR baseline, obtained by selectingthe first transcription suggested by the AS

Decision Making in the Medical Domain: Comparing the Effectiveness of GP-Generated Fuzzy Intelligent Structures

ABSTRACT: In this work, we examine the effectiveness of two intelligent models in medical domains. Namely, we apply grammar-guided genetic programming to produce fuzzy intelligent structures, such as fuzzy rule-based systems and fuzzy Petri nets, in medical data mining tasks. First, we use two context-free grammars to describe fuzzy rule-based systems and fuzzy Petri nets with genetic programming. Then, we apply cellular encoding in order to express the fuzzy Petri nets with arbitrary size and topology. The models are examined thoroughly in four real-world medical data sets. Results are presented in detail and the competitive advantages and drawbacks of the selected methodologies are discussed, in respect to the nature of each application domain. Conclusions are drawn on the effectiveness and efficiency of the presented approach

Structured parameter estimation for LFG-DOP using Backoff

Despite its state-of-the-art performance, the Data Oriented Parsing (DOP) model has been shown to suffer from biased parameter estimation, and the good performance seems more the result of ad hoc adjustments than correct probabilistic generalization over the data. In recent work, we developed a new estimation procedure, called Backoff Estimation, for DOP models that are based on Phrase-Structure annotations (so called Tree-DOP models). Backoff Estimation deviates from earlier methods in that it treats the model parameters as a highly structured space of correlated events (backoffs), rather than a set of disjoint events. In this paper we show that the problem of biased estimates also holds for DOP models that are based on Lexical-Functional Grammar annotations (i.e. LFG-DOP), and that the LFG-DOP parameters also constitute a hierarchically structured space. Subsequently, we adapt the Backoff Estimation algorithm from Tree-DOP to LFG-DOP models. Backoff Estimation turns out to be a natural solution to some of the specific problems of robust parsing under LFGDOP

Modeling RNA:DNA Hybrids with Formal Grammars

R-loops are nucleic acid structures consisting of a DNA:RNA hybrid and a DNA single strand. They form naturally during transcription when the nascent RNA hybridizes to the template DNA, forcing the coding DNA strand to wrap around the RNA:DNA duplex. Although formation of R-loops can have deleterious effects on genome integrity, there is evidence of their role as potential regulators of gene expression and DNA repair. Here we initiate an abstract model based on formal grammars to describe RNA:DNA interactions and the formation of R-loops. Separately we use a sliding window approach that accounts for properties of the DNA nucleotide sequence, such as C-richness and CG-skew, to identify segments favoring R-loops. We evaluate these properties on two DNA plasmids that are known to form R-loops and compare results with a recent energetics model from the Chédin Lab. Our abstract approach for R-loops is an initial step toward a more sophisticated framework which can take into account the effect of DNA topology on R-loop formation

Hybrid modeling, HMM/NN architectures, and protein applications

We describe a hybrid modeling approach where the parameters of a model are calculated and modulated by another model, typically a neural network (NN), to avoid both overfitting and underfitting. We develop the approach for the case of Hidden Markov Models (HMMs), by deriving a class of hybrid HMM/NN architectures. These architectures can be trained with unified algorithms that blend HMM dynamic programming with NN backpropagation. In the case of complex data, mixtures of HMMs or modulated HMMs must be used. NNs can then be applied both to the parameters of each single HMM, and to the switching or modulation of the models, as a function of input or context. Hybrid HMM/NN architectures provide a flexible NN parameterization for the control of model structure and complexity. At the same time, they can capture distributions that, in practice, are inaccessible to single HMMs. The HMM/NN hybrid approach is tested, in its simplest form, by constructing a model of the immunoglobulin protein family. A hybrid model is trained, and a multiple alignment derived, with less than a fourth of the number of parameters used with previous single HMMs