bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inferring duplications, losses, transfers and incomplete lineage sorting with nonbinary species trees
Authors: Stolzer Maureen , Lai Han , Xu Minli , Sathaye Deepa , Vernot Benjamin , Durand Dannie 
Published: September 2012

Abstract
Motivation: Gene duplication (D), transfer (T), loss (L) and incomplete lineage sorting (I) are crucial to the evolution of gene families and the emergence of novel functions. The history of these events can be inferred via comparison of gene and species trees, a process called reconciliation, yet current reconciliation algorithms model only a subset of these evolutionary processes.
Results: We present an algorithm to reconcile a binary gene tree with a nonbinary species tree under a DTLI parsimony criterion. This is the first reconciliation algorithm to capture all four evolutionary processes driving tree incongruence and the first to reconcile non-binary species trees with a transfer model. Our algorithm infers all optimal solutions and reports complete, temporally feasible event histories, giving the gene and species lineages in which each event occurred. It is fixed-parameter tractable, with polytime complexity when the maximum species outdegree is fixed. Application of our algorithms to prokaryotic and eukaryotic data show that use of an incomplete event model has substantial impact on the events inferred and resulting biological conclusions.
Availability: Our algorithms have been implemented in Notung, a freely available phylogenetic reconciliation software package, available at http://www.cs.cmu.edu/~durand/Notung.
Contact: mstolzer@andrew.cmu.edu
The architecture of the gene regulatory networks of different tissues
Authors: Li Jie , Hua Xu , Haubrock Martin , Wang Jin , Wingender Edgar 
Published: September 2012

Abstract
Summary: The great variety of human cell types in morphology and function is due to the diverse gene expression profiles that are governed by the distinctive regulatory networks in different cell types. It is still a challenging task to explain how the regulatory networks achieve the diversity of different cell types. Here, we report on our studies of the design principles of the tissue regulatory system by constructing the regulatory networks of eight human tissues, which subsume the regulatory interactions between transcription factors (TFs), microRNAs (miRNAs) and non-TF target genes. The results show that there are in-/out-hubs of high in-/out-degrees in tissue networks. Some hubs (strong hubs) maintain the hub status in all the tissues where they are expressed, whereas others (weak hubs), in spite of their ubiquitous expression, are hubs only in some tissues. The network motifs are mostly feed-forward loops. Some of them having no miRNAs are the common motifs shared by all tissues, whereas the others containing miRNAs are the tissue-specific ones owned by one or several tissues, indicating that the transcriptional regulation is more conserved across tissues than the post-transcriptional regulation. In particular, a common bow-tie framework was found that underlies the motif instances and shows diverse patterns in different tissues. Such bow-tie framework reflects the utilization efficiency of the regulatory system as well as its high variability in different tissues, and could serve as the model to further understand the structural adaptation of the regulatory system to the specific requirements of different cell functions.
Contact: edgar.wingender@bioinf.med.uni-goettingen.de; jwang@nju.edu.cn
Supplementary information: Supplementary data are available at Bioinformatics online.
Side-chain rotamer changes upon ligand binding: common, crucial, correlate with entropy and rearrange hydrogen bonding
Authors: Gaudreault Francis , Chartier Matthieu , Najmanovich Rafael 
Published: September 2012

Abstract
Motivation: Protein movements form a continuum from large domain rearrangements (including folding and restructuring) to side-chain rotamer changes and small rearrangements. Understanding side-chain flexibility upon binding is important to understand molecular recognition events and predict ligand binding.
Methods: In the present work, we developed a well-curated non-redundant dataset of 188 proteins in pairs of structures in the Apo (unbound) and Holo (bound) forms to study the extent and the factors that guide side-chain rotamer changes upon binding.
Results: Our analysis shows that side-chain rotamer changes are widespread with only 10% of binding sites displaying no conformational changes. Overall, at most five rotamer changes account for the observed movements in 90% of the cases. Furthermore, rotamer changes are essential in 32% of flexible binding sites. The different amino acids have a 11-fold difference in their probability to undergo changes. Side-chain flexibility represents an intrinsic property of amino acids as it correlates well with configurational entropy differences. Furthermore, on average b-factors and solvent accessible surface areas can discriminate flexible side-chains in the Apo form. Finally, there is a rearrangement of the hydrogen-bonding network upon binding primarily with a loss of H-bonds with water molecules and a gain of H-bonds with protein residues for flexible residues. Interestingly, only 25% of side chains capable of forming H-bonds do so with the ligand upon binding. In terms of drug design, this last result shows that there is a large number of potential interactions that may be exploited to modulate the specificity and sensitivity of inhibitors.
Contact: rafael.najmanovich@usherbrooke.ca
Uncovering the co-evolutionary network among prokaryotic genes
Authors: Cohen Ofir , Ashkenazy Haim , Burstein David , Pupko Tal 
Published: September 2012

AbstractMotivation: Correlated events of gains and losses enable inference of co-evolution relations. The reconstruction of the co-evolutionary interactions network in prokaryotic species may elucidate functional associations among genes.Results: We developed a novel probabilistic methodology for the detection of co-evolutionary interactions between pairs of genes. Using this method we inferred the co-evolutionary network among 4593 Clusters of Orthologous Genes (COGs). The number of co-evolutionary interactions substantially differed among COGs. Over 40% were found to co-evolve with at least one partner. We partitioned the network of co-evolutionary relations into clusters and uncovered multiple modular assemblies of genes with clearly defined functions. Finally, we measured the extent to which co-evolutionary relations coincide with other cellular relations such as genomic proximity, gene fusion propensity, co-expression, protein–protein interactions and metabolic connections. Our results show that co-evolutionary relations only partially overlap with these other types of networks. Our results suggest that the inferred co-evolutionary network in prokaryotes is highly informative towards revealing functional relations among genes, often showing signals that cannot be extracted from other network types.Availability and implementation: Available under GPL license as open source.Contact: talp@post.tau.ac.il.Supplementary information: Supplementary data are available at Bioinformatics online.
Genomic context analysis reveals dense interaction network between vertebrate ultraconserved non-coding elements
Authors: Dimitrieva Slavica , Bucher Philipp 
Published: September 2012

Abstract
Motivation: Genomic context analysis, also known as phylogenetic profiling, is widely used to infer functional interactions between proteins but rarely applied to non-coding cis-regulatory DNA elements. We were wondering whether this approach could provide insights about utlraconserved non-coding elements (UCNEs). These elements are organized as large clusters, so-called gene regulatory blocks (GRBs) around key developmental genes. Their molecular functions and the reasons for their high degree of conservation remain enigmatic.
Results: In a special setting of genomic context analysis, we analyzed the fate of GRBs after a whole-genome duplication event in five fish genomes. We found that in most cases all UCNEs were retained together as a single block, whereas the corresponding target genes were often retained in two copies, one completely devoid of UCNEs. This ‘winner-takes-all’ pattern suggests that UCNEs of a GRB function in a highly cooperative manner. We propose that the multitude of interactions between UCNEs is the reason for their extreme sequence conservation.
Supplementary information: Supplementary data are available at Bioinformatics online and at http://ccg.vital-it.ch/ucne/
SANS: high-throughput retrieval of protein sequences allowing 50% mismatches
Authors: Koskinen J. Patrik , Holm Liisa 
Published: September 2012

Abstract
Motivation: The genomic era in molecular biology has brought on a rapidly widening gap between the amount of sequence data and first-hand experimental characterization of proteins. Fortunately, the theory of evolution provides a simple solution: functional and structural information can be transferred between homologous proteins. Sequence similarity searching followed by k-nearest neighbor classification is the most widely used tool to predict the function or structure of anonymous gene products that come out of genome sequencing projects.
Results: We present a novel word filter, suffix array neighborhood search (SANS), to identify protein sequence similarities in the range of 50–100% identity with sensitivity comparable to BLAST and 10 times the speed of USEARCH. In contrast to these previous approaches, the complexity of the search is proportional only to the length of the query sequence and independent of database size, enabling fast searching and functional annotation into the future despite rapidly expanding databases.
Availability and implementation: The software is freely available to non-commercial users from our website http://ekhidna.biocenter.helsinki.fi/downloads/sans.
Contact: liisa.holm@helsinki.fi.
Impact of ontology evolution on functional analyses
Authors: Groß Anika , Hartung Michael , Prüfer Kay , Kelso Janet , Rahm Erhard 
Published: September 2012

Abstract
Motivation: Ontologies are used in the annotation and analysis of biological data. As knowledge accumulates, ontologies and annotation undergo constant modifications to reflect this new knowledge. These modifications may influence the results of statistical applications such as functional enrichment analyses that describe experimental data in terms of ontological groupings. Here, we investigate to what degree modifications of the Gene Ontology (GO) impact these statistical analyses for both experimental and simulated data. The analysis is based on new measures for the stability of result sets and considers different ontology and annotation changes.
Results: Our results show that past changes in the GO are non-uniformly distributed over different branches of the ontology. Considering the semantic relatedness of significant categories in analysis results allows a more realistic stability assessment for functional enrichment studies. We observe that the results of term-enrichment analyses tend to be surprisingly stable despite changes in ontology and annotation.
Contact: gross@informatik.uni-leipzig.de
Supplementary information: Supplementary Data are available at Bioinformatics online.
HighSSR: high-throughput SSR characterization and locus development from next-gen sequencing data
Authors: Churbanov Alexander , Ryan Rachael , Hasan Nabeeh , Bailey Donovan , Chen Haofeng , Milligan Brook , Houde Peter 
Published: September 2012

Abstract
Motivation: Microsatellites are among the most useful genetic markers in population biology. High-throughput sequencing of microsatellite-enriched libraries dramatically expedites the traditional process of screening recombinant libraries for microsatellite markers. However, sorting through millions of reads to distill high-quality polymorphic markers requires special algorithms tailored to tolerate sequencing errors in locus reconstruction, distinguish paralogous loci, rarify raw reads originating from the same amplicon and sort out various artificial fragments resulting from recombination or concatenation of auxiliary adapters. Existing programs warrant improvement.
Results: We describe a microsatellite prediction framework named HighSSR for microsatellite genotyping based on high-throughput sequencing. We demonstrate the utility of HighSSR in comparison to Roche gsAssembler on two Roche 454 GS FLX runs. The majority of the HighSSR-assembled loci were reliably mapped against model organism reference genomes. HighSSR demultiplexes pooled libraries, assesses locus polymorphism and implements Primer3 for the design of PCR primers flanking polymorphic microsatellite loci. As sequencing costs drop and permit the analysis of all project samples on next-generation platforms, this framework can also be used for direct simple sequence repeats genotyping.
Availability: http://code.google.com/p/highssr/
Contact: alexander@big.ac.cn
Supplementary Information: Supplementary data are available at Bioinformatics online.
Genome-wide in silico prediction of gene expression
Authors: McLeay Robert C. , Lesluyes Tom , Cuellar Partida Gabriel , Bailey Timothy L. 
Published: September 2012

Abstract
Motivation: Modelling the regulation of gene expression can provide insight into the regulatory roles of individual transcription factors (TFs) and histone modifications. Recently, Ouyang et al. in 2009 modelled gene expression levels in mouse embryonic stem (mES) cells using in vivo ChIP-seq measurements of TF binding. ChIP-seq TF binding data, however, are tissue-specific and relatively difficult to obtain. This limits the applicability of gene expression models that rely on ChIP-seq TF binding data.
Results: In this study, we build regression-based models that relate gene expression to the binding of 12 different TFs, 7 histone modifications and chromatin accessibility (DNase I hypersensitivity) in two different tissues. We find that expression models based on computationally predicted TF binding can achieve similar accuracy to those using in vivo TF binding data and that including binding at weak sites is critical for accurate prediction of gene expression. We also find that incorporating histone modification and chromatin accessibility data results in additional accuracy. Surprisingly, we find that models that use no TF binding data at all, but only histone modification and chromatin accessibility data, can be as (or more) accurate than those based on in vivo TF binding data.
Availability and implementation: All scripts, motifs and data presented in this article are available online at http://research.imb.uq.edu.au/t.bailey/supplementary_data/McLeay2011a.
Contact: t.bailey@imb.uq.edu.au
Supplementary information: Supplementary data are available at Bioinformatics online.
A linear programming model for protein inference problem in shotgun proteomics
Authors: Huang Ting , He Zengyou 
Published: September 2012

Abstract
Motivation: Assembling peptides identified from tandem mass spectra into a list of proteins, referred to as protein inference, is an important issue in shotgun proteomics. The objective of protein inference is to find a subset of proteins that are truly present in the sample. Although many methods have been proposed for protein inference, several issues such as peptide degeneracy still remain unsolved.
Results: In this article, we present a linear programming model for protein inference. In this model, we use a transformation of the joint probability that each peptide/protein pair is present in the sample as the variable. Then, both the peptide probability and protein probability can be expressed as a formula in terms of the linear combination of these variables. Based on this simple fact, the protein inference problem is formulated as an optimization problem: minimize the number of proteins with non-zero probabilities under the constraint that the difference between the calculated peptide probability and the peptide probability generated from peptide identification algorithms should be less than some threshold. This model addresses the peptide degeneracy issue by forcing some joint probability variables involving degenerate peptides to be zero in a rigorous manner. The corresponding inference algorithm is named as ProteinLP. We test the performance of ProteinLP on six datasets. Experimental results show that our method is competitive with the state-of-the-art protein inference algorithms.
Availability: The source code of our algorithm is available at: https://sourceforge.net/projects/prolp/.
Contact: zyhe@dlut.edu.cn
Supplementary information: Supplementary data are available at Bioinformatics Online.
Comb-p: software for combining, analyzing, grouping and correcting spatially correlatedP-values
Authors: Pedersen Brent S. , Schwartz David A. , Yang Ivana V. , Kechris Katerina J. 
Published: September 2012

AbstractSummary: comb-p is a command-line tool and a python library that manipulates BED files of possibly irregularly spaced P-values and (1) calculates auto-correlation, (2) combines adjacent P-values, (3) performs false discovery adjustment, (4) finds regions of enrichment (i.e. series of adjacent low P-values) and (5) assigns significance to those regions. In addition, tools are provided for visualization and assessment. We provide validation and example uses on bisulfite-seq with P-values from Fisher’s exact test, tiled methylation probes using a linear model and Dam-ID for chromatin binding using moderated t-statistics. Because the library accepts input in a simple, standardized format and is unaffected by the origin of the P-values, it can be used for a wide variety of applications.Availability: comb-p is maintained under the BSD license. The documentation and implementation are available at https://github.com/brentp/combined-pvalues.Contact: bpederse@gmail.com
The experiences of people with learning disabilities on social networking sites
Authors: Holmes Katrina M. , O'Loughlin Nessa 
Published: September 2012

Accessible summary

Lots of people use the Internet to make friends and talk to friends.
We behave in certain ways because of how people talk to us and treat us.
Some people use Facebook on the Internet to stay in touch with their friends and make new friends. This can be a very good experience.
Some other people have had problems when using social networking sites like Facebook.
Some people have been bullied online and some have had money taken off them.
We spoke to three people who have had good and bad things happen on Facebook.
We have suggested some ideas on how to help people with these problems.

SummarySocial identity has traditionally been established through face‐to‐face interactions. However, in recent times, social networking sites have provided an additional medium through which social identities can be developed and explored. Social networking has become increasingly popular over the past decade, attracting millions of active users worldwide. These sites offer an opportunity to maintain friendships, create new friendships and even date. The following article highlights the positive and negative experiences of three people with learning disabilities using social networking sites. The negative experiences reported by our service users highlighted areas of concern with regard to their safety. As a result, a therapeutic group was formed to address these online experiences and provide practical and emotional support. At the end of the group, service users reported that they were more confident about discussing and problem solving issues around online use.
Association of dietary and genetic factors related to one‐carbon metabolism with global methylation level of leukocyte DNA
Authors: Ono Hiroe , Iwasaki Motoki , Kuchiba Aya , Kasuga Yoshio , Yokoyama Shiro , Onuma Hiroshi , Nishimura Hideki , Kusama Ritsu , Ohnami Sumiko , Sakamoto Hiromi , Yoshida Teruhiko , Tsugane Shoichiro 
Published: September 2012

Global hypomethylation of leukocyte DNA has been associated with an increased risk of cancer. As dietary and genetic factors related to one‐carbon metabolism may influence both the methylation and synthesis of DNA, we investigated associations between these factors and the global methylation level of peripheral blood leukocyte DNA based on a cross‐sectional study of 384 Japanese women. Dietary intake of folate and vitamins B2, B6, and B12 was assessed with a validated semiquantitative food frequency questionnaire. Five polymorphisms in methylenetetrahydrofolate reductase (MTHFR) (rs1801133 and rs1801131), methionine synthase (MTR) (rs1805087), and methionine synthase reductase (MTRR) (rs10380 and rs162049) were genotyped. Global DNA methylation of leukocyte DNA was quantified using Luminometric Methylation Assay. A linear trend of association between methylation and dietary and genetic factors was evaluated by regression coefficients in a multivariable linear regression model. Mean global methylation level (standard deviation) was 70.2% (3.4) and range was from 59.0% to 81.2%. Global methylation level significantly decreased by 0.36% (95% confidence interval, 0.03–0.69) per quartile category for folate level. Subgroup analysis suggested that alcohol drinking modified the association between folate intake and global methylation level (Pinteraction = 0.01). However, no statistically significant association was observed for intake of vitamins B2, B6, and B12, alcohol consumption, or five single nucleotide polymorphisms of MTHFR, MTR, and MTRR. We found that higher folate intake was significantly associated with a lower level of global methylation of leukocyte DNA in a group of healthy Japanese females.
Kuguaglycoside C, a constituent of Momordica charantia, induces caspase‐independent cell death of neuroblastoma cells
Authors: Tabata Keiichi , Hamano Aoi , Akihisa Toshihiro , Suzuki Takashi 
Published: September 2012

Kuguaglycoside C is a triterpene glycoside isolated from the leaves of Momordica charantia, and the biological effects of this compound remain almost unknown. We investigated the anti;?>cancer effect of kuguaglycoside C against human neuroblastoma IMR‐32 cells. In the MTT assay, kuguaglycoside C induced significant cytotoxicity against the IMR‐32 cells (IC50: 12.6 μM) after 48 h treatment. Although examination by Hoechst 33342 staining revealed that kuguaglycoside C induced nuclear shrinkage at a high concentration (100 μM), no apoptotic bodies were observed on flow cytometry. No activation of caspase‐3 or caspase‐9 was observed at the effective concentration (30 μM) of kuguaglycoside C. On the other hand, the substance significantly decreased the expression of survivin and cleaved poly (ADP‐ribose) polymerase (PARP). Kuguaglycoside C also significantly increased the expression and cleavage of apoptosis‐inducing factor (AIF). Moreover, kuguaglycoside C was found to induce caspase‐independent DNA cleavage in the dual‐fluorescence apoptosis detection assay. These results suggest that kuguaglycoside C induces caspase‐independent cell death, and is involved, at least in part, in the mechanism underlying cell necroptosis.