Classifying pairs with trees for supervised biological network inference

Networks are ubiquitous in biology and computational approaches have been largely investigated for their inference. In particular, supervised machine learning methods can be used to complete a partially known network by integrating various measurements. Two main supervised frameworks have been proposed: the local approach, which trains a separate model for each network node, and the global approach, which trains a single model over pairs of nodes. Here, we systematically investigate, theoretically and empirically, the exploitation of tree-based ensemble methods in the context of these two approaches for biological network inference. We first formalize the problem of network inference as classification of pairs, unifying in the process homogeneous and bipartite graphs and discussing two main sampling schemes. We then present the global and the local approaches, extending the later for the prediction of interactions between two unseen network nodes, and discuss their specializations to tree-based ensemble methods, highlighting their interpretability and drawing links with clustering techniques. Extensive computational experiments are carried out with these methods on various biological networks that clearly highlight that these methods are competitive with existing methods.Comment: 22 page

Network-based approaches for linking metabolism with environment

Genome-wide metabolic maps allow the development of network-based computational approaches for linking an organism with its biochemical habitat

Exploiting gene deletion fitness effects in yeast to understand the modular architecture of protein complexes under different growth conditions

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Understanding how individual genes contribute towards the fitness of an organism is a fundamental problem in biology. Although recent genome-wide screens have generated abundant data on quantitative fitness for single gene knockouts, very few studies have systematically integrated other types of biological information to understand how and why deletion of specific genes give rise to a particular fitness effect. In this study, we combine quantitative fitness data for single gene knock-outs in yeast with large-scale interaction discovery experiments to understand the effect of gene deletion on the modular architecture of protein complexes, under different growth conditions. Results Our analysis reveals that genes in complexes show more severe fitness effects upon deletion than other genes but, in contrast to what has been observed in binary protein-protein interaction networks, we find that this is not related to the number of complexes in which they are present. We also find that, in general, the core and attachment components of protein complexes are equally important for the complex machinery to function. However, when quantifying the importance of core and attachments in single complex variations, or isoforms, we observe that this global trend originates from either the core or the attachment components being more important for strain fitness, both being equally important or both being dispensable. Finally, our study reveals that different isoforms of a complex can exhibit distinct fitness patterns across growth conditions. Conclusion This study presents a powerful approach to unveil the molecular basis for various complex phenotypic profiles observed in gene deletion experiments. It also highlights some interesting cases of potential functional compensation between protein paralogues and suggests a new piece to fit into the histone-code puzzle.Published versio

Characterization of Nepalese Barley Gene Pool for Leaf Rust Resistance

Barley (Hordeum vulagare L) is the major crop for the people living in the high hills and mountainous region of Nepal. Leaf rust (caused by Puccinia hordei) is one of the major production threats for barley cultivation. A lot of variation can be observed on Nepalese barley accessions with respect to leaf rust resistance characteristics. Two hundred and forty one barley accessions were screened for leaf rust resistance characteristics on heading stage at Khumaltar, Lalitpur, Nepal. Among them, one hundred and nine Nepalese barley accessions showing promising for disease resistance were screened using six SSR markers linked to leaf rust resistance genes. Bonus and Local Jau was used as the resistant and susceptible check respectively. Leaf rust resistance genes Rph1, Rph2, Rph3, Rph7, QBLR-P and QTL on chromosome 5HS were detected on Nepalese barley accessions using respective SSR markers. Eight Nepalese barley accessions showed presence of three and more leaf rust resistant genes. The poor relationship between the field disease resistance and molecular markers linked with specific leaf rust resistance gene proved that Nepalese barley gene pool contains other leaf resistance genes

ESTIMATION OF LIPID PROFILE AND ASSESSMENT OF CARDIOVASCULAR RISK IN SMOKERS BY USING NEW ATHEROGENIC INDICES

Objective: Smoking habit leads to elevated levels of lipid profile thus increasing the cardiovascular disease risk in coronary heart disease. The aim ofstudy is undertaken to evaluate plasma lipid profile, of the male smoker with non-smoker's healthy matched control and assessing the cardiovascularrisk by using new atherogenic indices.Methods: Fasting blood samples were collected form both cases and controls and estimation of lipid profile by using by using autoanalyzer. A detailedphysical and anthropometric parameters information was collected form each participant subjects.Results: Plasma total cholesterol (TC) (221.52±8.34), triglyceride (TG) (274.94±28.70) low density lipoprotein cholesterol (LDL-c) (129.22±7.76),very LDL-c (VLDL-c) (54.98±5.74) and non-high-density lipoprotein cholesterol NonHDL-c (HDL-c) (183.26±7.58) in smokers subjects, which weresignificantly (p<0.0001) higher compared with non-smokers, while HDL-c significantly (38.25±1.34; p<0.001) decreased in smokers as comparedto non-smokers. Further, atherogenic ratios like, Castelli's risk index (CRI-I)=TC/HDL-c, CRI-II=LDL-c/HDL-c, atherogenic coefficient = (TC–HDL-c)/HDL-c TG/HDL-c ratio, and atherogenic index of plasma =log (TG/HDL-c) were calculated for individual subjects by using lipid profile. All these lipidratio are significantly (p<0.0001) in smoker group.Conclusion: Our conclusion, these ratio's could be used for identifying individual at higher risk of cardiovascular disease in the clinical practicesespecially, when the absolute values of lipid profile seem normal or higher and not markedly deranged or in centers with insufficient resources.Keywords: Cigarette smoking, Lipid profile, Cardiovascular risk, Atherogenic indices

Spial: analysis of subtype-specific features in multiple sequence alignments of proteins

Motivation: Spial (Specificity in alignments) is a tool for the comparative analysis of two alignments of evolutionarily related sequences that differ in their function, such as two receptor subtypes. It highlights functionally important residues that are either specific to one of the two alignments or conserved across both alignments. It permits visualization of this information in three complementary ways: by colour-coding alignment positions, by sequence logos and optionally by colour-coding the residues of a protein structure provided by the user. This can aid in the detection of residues that are involved in the subtype-specific interaction with a ligand, other proteins or nucleic acids. Spial may also be used to detect residues that may be post-translationally modified in one of the two sets of sequences. Availability: http://www.mrc-lmb.cam.ac.uk/genomes/spial/; supplementary information is available at http://www.mrc-lmb.cam.ac.uk/genomes/spial/help.html Contact: [email protected]

Hierarchy and Feedback in the Evolution of the E. coli Transcription Network

The E.coli transcription network has an essentially feedforward structure, with, however, abundant feedback at the level of self-regulations. Here, we investigate how these properties emerged during evolution. An assessment of the role of gene duplication based on protein domain architecture shows that (i) transcriptional autoregulators have mostly arisen through duplication, while (ii) the expected feedback loops stemming from their initial cross-regulation are strongly selected against. This requires a divergent coevolution of the transcription factor DNA-binding sites and their respective DNA cis-regulatory regions. Moreover, we find that the network tends to grow by expansion of the existing hierarchical layers of computation, rather than by addition of new layers. We also argue that rewiring of regulatory links due to mutation/selection of novel transcription factor/DNA binding interactions appears not to significantly affect the network global hierarchy, and that horizontally transferred genes are mainly added at the bottom, as new target nodes. These findings highlight the important evolutionary roles of both duplication and selective deletion of crosstalks between autoregulators in the emergence of the hierarchical transcription network of E.coli.Comment: to appear in PNA

p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response.

The human DNA damage response (DDR) triggers profound changes in gene expression, whose nature and regulation remain uncertain. Although certain micro-(mi)RNA species including miR34, miR-18, miR-16 and miR-143 have been implicated in the DDR, there is as yet no comprehensive description of genome-wide changes in the expression of miRNAs triggered by DNA breakage in human cells. We have used next-generation sequencing (NGS), combined with rigorous integrative computational analyses, to describe genome-wide changes in the expression of miRNAs during the human DDR. The changes affect 150 of 1523 miRNAs known in miRBase v18 from 4-24 h after the induction of DNA breakage, in cell-type dependent patterns. The regulatory regions of the most-highly regulated miRNA species are enriched in conserved binding sites for p53. Indeed, genome-wide changes in miRNA expression during the DDR are markedly altered in TP53-/- cells compared to otherwise isogenic controls. The expression levels of certain damage-induced, p53-regulated miRNAs in cancer samples correlate with patient survival. Our work reveals genome-wide and cell type-specific alterations in miRNA expression during the human DDR, which are regulated by the tumor suppressor protein p53. These findings provide a genomic resource to identify new molecules and mechanisms involved in the DDR, and to examine their role in tumor suppression and the clinical outcome of cancer patients