bluuebunny/crossref_metadata_2025_split huggingface dataset:
Jumping across biomedical contexts using compressive data fusion
Authors: Zitnik Marinka , Zupan Blaz 
Published: June 2016

Abstract
Motivation: The rapid growth of diverse biological data allows us to consider interactions between a variety of objects, such as genes, chemicals, molecular signatures, diseases, pathways and environmental exposures. Often, any pair of objects—such as a gene and a disease—can be related in different ways, for example, directly via gene–disease associations or indirectly via functional annotations, chemicals and pathways. Different ways of relating these objects carry different semantic meanings. However, traditional methods disregard these semantics and thus cannot fully exploit their value in data modeling.
Results: We present Medusa, an approach to detect size-k modules of objects that, taken together, appear most significant to another set of objects. Medusa operates on large-scale collections of heterogeneous datasets and explicitly distinguishes between diverse data semantics. It advances research along two dimensions: it builds on collective matrix factorization to derive different semantics, and it formulates the growing of the modules as a submodular optimization program. Medusa is flexible in choosing or combining semantic meanings and provides theoretical guarantees about detection quality. In a systematic study on 310 complex diseases, we show the effectiveness of Medusa in associating genes with diseases and detecting disease modules. We demonstrate that in predicting gene–disease associations Medusa compares favorably to methods that ignore diverse semantic meanings. We find that the utility of different semantics depends on disease categories and that, overall, Medusa recovers disease modules more accurately when combining different semantics.
Availability and implementation: Source code is at http://github.com/marinkaz/medusa
Contact: marinka@cs.stanford.edu, blaz.zupan@fri.uni-lj.si
PHOCOS: inferring multi-feature phenotypic crosstalk networks
Authors: Deng Yue , Altschuler Steven J. , Wu Lani F. 
Published: June 2016

Abstract
Motivation: Quantification of cellular changes to perturbations can provide a powerful approach to infer crosstalk among molecular components in biological networks. Existing crosstalk inference methods conduct network-structure learning based on a single phenotypic feature (e.g. abundance) of a biomarker. These approaches are insufficient for analyzing perturbation data that can contain information about multiple features (e.g. abundance, activity or localization) of each biomarker.
Results: We propose a computational framework for inferring phenotypic crosstalk (PHOCOS) that is suitable for high-content microscopy or other modalities that capture multiple phenotypes per biomarker. PHOCOS uses a robust graph-learning paradigm to predict direct effects from potential indirect effects and identify errors owing to noise or missing links. The result is a multi-feature, sparse network that parsimoniously captures direct and strong interactions across phenotypic attributes of multiple biomarkers. We use simulated and biological data to demonstrate the ability of PHOCOS to recover multi-attribute crosstalk networks from cellular perturbation assays.
Availability and implementation: PHOCOS is available in open source at https://github.com/AltschulerWu-Lab/PHOCOS
Contact: steven.altschuler@ucsf.edu or lani.wu@ucsf.edu
Prediction of ribosome footprint profile shapes from transcript sequences
Authors: Liu Tzu-Yu , Song Yun S. 
Published: June 2016

AbstractMotivation: Ribosome profiling is a useful technique for studying translational dynamics and quantifying protein synthesis. Applications of this technique have shown that ribosomes are not uniformly distributed along mRNA transcripts. Understanding how each transcript-specific distribution arises is important for unraveling the translation mechanism.Results: Here, we apply kernel smoothing to construct predictive features and build a sparse model to predict the shape of ribosome footprint profiles from transcript sequences alone. Our results on Saccharomyces cerevisiae data show that the marginal ribosome densities can be predicted with high accuracy. The proposed novel method has a wide range of applications, including inferring isoform-specific ribosome footprints, designing transcripts with fast translation speeds and discovering unknown modulation during translation.Availability and implementation: A software package called riboShape is freely available at https://sourceforge.net/projects/riboshapeContact: yss@berkeley.edu
Convolutional neural network architectures for predicting DNA–protein binding
Authors: Zeng Haoyang , Edwards Matthew D. , Liu Ge , Gifford David K. 
Published: June 2016

Abstract
Motivation: Convolutional neural networks (CNN) have outperformed conventional methods in modeling the sequence specificity of DNA–protein binding. Yet inappropriate CNN architectures can yield poorer performance than simpler models. Thus an in-depth understanding of how to match CNN architecture to a given task is needed to fully harness the power of CNNs for computational biology applications.
Results: We present a systematic exploration of CNN architectures for predicting DNA sequence binding using a large compendium of transcription factor datasets. We identify the best-performing architectures by varying CNN width, depth and pooling designs. We find that adding convolutional kernels to a network is important for motif-based tasks. We show the benefits of CNNs in learning rich higher-order sequence features, such as secondary motifs and local sequence context, by comparing network performance on multiple modeling tasks ranging in difficulty. We also demonstrate how careful construction of sequence benchmark datasets, using approaches that control potentially confounding effects like positional or motif strength bias, is critical in making fair comparisons between competing methods. We explore how to establish the sufficiency of training data for these learning tasks, and we have created a flexible cloud-based framework that permits the rapid exploration of alternative neural network architectures for problems in computational biology.
Availability and Implementation: All the models analyzed are available at http://cnn.csail.mit.edu.
Contact: gifford@mit.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
A novel method for discovering local spatial clusters of genomic regions with functional relationships from DNA contact maps
Authors: Hu Xihao , Shi Christina Huan , Yip Kevin Y. 
Published: June 2016

Abstract
Motivation: The three-dimensional structure of genomes makes it possible for genomic regions not adjacent in the primary sequence to be spatially proximal. These DNA contacts have been found to be related to various molecular activities. Previous methods for analyzing DNA contact maps obtained from Hi-C experiments have largely focused on studying individual interactions, forming spatial clusters composed of contiguous blocks of genomic locations, or classifying these clusters into general categories based on some global properties of the contact maps.
Results: Here, we describe a novel computational method that can flexibly identify small clusters of spatially proximal genomic regions based on their local contact patterns. Using simulated data that highly resemble Hi-C data obtained from real genome structures, we demonstrate that our method identifies spatial clusters that are more compact than methods previously used for clustering genomic regions based on DNA contact maps. The clusters identified by our method enable us to confirm functionally related genomic regions previously reported to be spatially proximal in different species. We further show that each genomic region can be assigned a numeric affinity value that indicates its degree of participation in each local cluster, and these affinity values correlate quantitatively with DNase I hypersensitivity, gene expression, super enhancer activities and replication timing in a cell type specific manner. We also show that these cluster affinity values can precisely define boundaries of reported topologically associating domains, and further define local sub-domains within each domain.
Availability and implementation: The source code of BNMF and tutorials on how to use the software to extract local clusters from contact maps are available at http://yiplab.cse.cuhk.edu.hk/bnmf/ .
Contact: kevinyip@cse.cuhk.edu.hk
Supplementary information: Supplementary data are available at Bioinformatics online.
Finding correct protein–protein docking models using ProQDock
Authors: Basu Sankar , Wallner Björn 
Published: June 2016

AbstractMotivation: Protein–protein interactions are a key in virtually all biological processes. For a detailed understanding of the biological processes, the structure of the protein complex is essential. Given the current experimental techniques for structure determination, the vast majority of all protein complexes will never be solved by experimental techniques. In lack of experimental data, computational docking methods can be used to predict the structure of the protein complex. A common strategy is to generate many alternative docking solutions (atomic models) and then use a scoring function to select the best. The success of the computational docking technique is, to a large degree, dependent on the ability of the scoring function to accurately rank and score the many alternative docking models.Results: Here, we present ProQDock, a scoring function that predicts the absolute quality of docking model measured by a novel protein docking quality score (DockQ). ProQDock uses support vector machines trained to predict the quality of protein docking models using features that can be calculated from the docking model itself. By combining different types of features describing both the protein–protein interface and the overall physical chemistry, it was possible to improve the correlation with DockQ from 0.25 for the best individual feature (electrostatic complementarity) to 0.49 for the final version of ProQDock. ProQDock performed better than the state-of-the-art methods ZRANK and ZRANK2 in terms of correlations, ranking and finding correct models on an independent test set. Finally, we also demonstrate that it is possible to combine ProQDock with ZRANK and ZRANK2 to improve performance even further.Availability and implementation: http://bioinfo.ifm.liu.se/ProQDockContact: bjornw@ifm.liu.seSupplementary information: Supplementary data are available at Bioinformatics online.
RCK: accurate and efficient inference of sequence- and structure-based protein–RNA binding models from RNAcompete data
Authors: Orenstein Yaron , Wang Yuhao , Berger Bonnie 
Published: June 2016

Abstract
Motivation: Protein–RNA interactions, which play vital roles in many processes, are mediated through both RNA sequence and structure. CLIP-based methods, which measure protein–RNA binding in vivo, suffer from experimental noise and systematic biases, whereas in vitro experiments capture a clearer signal of protein RNA-binding. Among them, RNAcompete provides binding affinities of a specific protein to more than 240 000 unstructured RNA probes in one experiment. The computational challenge is to infer RNA structure- and sequence-based binding models from these data. The state-of-the-art in sequence models, Deepbind, does not model structural preferences. RNAcontext models both sequence and structure preferences, but is outperformed by GraphProt. Unfortunately, GraphProt cannot detect structural preferences from RNAcompete data due to the unstructured nature of the data, as noted by its developers, nor can it be tractably run on the full RNACompete dataset.
Results: We develop RCK, an efficient, scalable algorithm that infers both sequence and structure preferences based on a new k-mer based model. Remarkably, even though RNAcompete data is designed to be unstructured, RCK can still learn structural preferences from it. RCK significantly outperforms both RNAcontext and Deepbind in in vitro binding prediction for 244 RNAcompete experiments. Moreover, RCK is also faster and uses less memory, which enables scalability. While currently on par with existing methods in in vivo binding prediction on a small scale test, we demonstrate that RCK will increasingly benefit from experimentally measured RNA structure profiles as compared to computationally predicted ones. By running RCK on the entire RNAcompete dataset, we generate and provide as a resource a set of protein–RNA structure-based models on an unprecedented scale.
Availability and Implementation: Software and models are freely available at http://rck.csail.mit.edu/
Contact: bab@mit.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
An algorithm for computing the gene tree probability under the multispecies coalescent and its application in the inference of population tree
Authors: Wu Yufeng 
Published: June 2016

Abstract
Motivation: Gene tree represents the evolutionary history of gene lineages that originate from multiple related populations. Under the multispecies coalescent model, lineages may coalesce outside the species (population) boundary. Given a species tree (with branch lengths), the gene tree probability is the probability of observing a specific gene tree topology under the multispecies coalescent model. There are two existing algorithms for computing the exact gene tree probability. The first algorithm is due to Degnan and Salter, where they enumerate all the so-called coalescent histories for the given species tree and the gene tree topology. Their algorithm runs in exponential time in the number of gene lineages in general. The second algorithm is the STELLS algorithm (2012), which is usually faster but also runs in exponential time in almost all the cases.
Results: In this article, we present a new algorithm, called CompactCH, for computing the exact gene tree probability. This new algorithm is based on the notion of compact coalescent histories: multiple coalescent histories are represented by a single compact coalescent history. The key advantage of our new algorithm is that it runs in polynomial time in the number of gene lineages if the number of populations is fixed to be a constant. The new algorithm is more efficient than the STELLS algorithm both in theory and in practice when the number of populations is small and there are multiple gene lineages from each population. As an application, we show that CompactCH can be applied in the inference of population tree (i.e. the population divergence history) from population haplotypes. Simulation results show that the CompactCH algorithm enables efficient and accurate inference of population trees with much more haplotypes than a previous approach.
Availability: The CompactCH algorithm is implemented in the STELLS software package, which is available for download at http://www.engr.uconn.edu/ywu/STELLS.html.
Contact: ywu@engr.uconn.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
An integer programming framework for inferring disease complexes from network data
Authors: Mazza Arnon , Klockmeier Konrad , Wanker Erich , Sharan Roded 
Published: June 2016

AbstractMotivation: Unraveling the molecular mechanisms that underlie disease calls for methods that go beyond the identification of single causal genes to inferring larger protein assemblies that take part in the disease process.Results: Here, we develop an exact, integer-programming-based method for associating protein complexes with disease. Our approach scores proteins based on their proximity in a protein–protein interaction network to a prior set that is known to be relevant for the studied disease. These scores are combined with interaction information to infer densely interacting protein complexes that are potentially disease-associated. We show that our method outperforms previous ones and leads to predictions that are well supported by current experimental data and literature knowledge.Availability and Implementation: The datasets we used, the executables and the results are available at www.cs.tau.ac.il/roded/disease_complexes.zipContact: roded@post.tau.ac.il
Structure-based prediction of transcription factor binding specificity using an integrative energy function
Authors: Farrel Alvin , Murphy Jonathan , Guo Jun-tao 
Published: June 2016

Abstract
Transcription factors (TFs) regulate gene expression through binding to specific target DNA sites. Accurate annotation of transcription factor binding sites (TFBSs) at genome scale represents an essential step toward our understanding of gene regulation networks. In this article, we present a structure-based method for computational prediction of TFBSs using a novel, integrative energy (IE) function. The new energy function combines a multibody (MB) knowledge-based potential and two atomic energy terms (hydrogen bond and π interaction) that might not be accurately captured by the knowledge-based potential owing to the mean force nature and low count problem. We applied the new energy function to the TFBS prediction using a non-redundant dataset that consists of TFs from 12 different families. Our results show that the new IE function improves the prediction accuracy over the knowledge-based, statistical potentials, especially for homeodomain TFs, the second largest TF family in mammals.
Contact: jguo4@uncc.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Genome assembly from synthetic long read clouds
Authors: Kuleshov Volodymyr , Snyder Michael P. , Batzoglou Serafim 
Published: June 2016

Abstract
Motivation: Despite rapid progress in sequencing technology, assembling de novo the genomes of new species as well as reconstructing complex metagenomes remains major technological challenges. New synthetic long read (SLR) technologies promise significant advances towards these goals; however, their applicability is limited by high sequencing requirements and the inability of current assembly paradigms to cope with combinations of short and long reads.
Results: Here, we introduce Architect, a new de novo scaffolder aimed at SLR technologies. Unlike previous assembly strategies, Architect does not require a costly subassembly step; instead it assembles genomes directly from the SLR’s underlying short reads, which we refer to as read clouds . This enables a 4- to 20-fold reduction in sequencing requirements and a 5-fold increase in assembly contiguity on both genomic and metagenomic datasets relative to state-of-the-art assembly strategies aimed directly at fully subassembled long reads.
Availability and Implementation: Our source code is freely available at https://github.com/kuleshov/architect .
Contact: kuleshov@stanford.edu
Faster and more accurate graphical model identification of tandem mass spectra using trellises
Authors: Wang Shengjie , Halloran John T. , Bilmes Jeff A. , Noble William S. 
Published: June 2016

AbstractTandem mass spectrometry (MS/MS) is the dominant high throughput technology for identifying and quantifying proteins in complex biological samples. Analysis of the tens of thousands of fragmentation spectra produced by an MS/MS experiment begins by assigning to each observed spectrum the peptide that is hypothesized to be responsible for generating the spectrum. This assignment is typically done by searching each spectrum against a database of peptides. To our knowledge, all existing MS/MS search engines compute scores individually between a given observed spectrum and each possible candidate peptide from the database. In this work, we use a trellis , a data structure capable of jointly representing a large set of candidate peptides, to avoid redundantly recomputing common sub-computations among different candidates. We show how trellises may be used to significantly speed up existing scoring algorithms, and we theoretically quantify the expected speedup afforded by trellises. Furthermore, we demonstrate that compact trellis representations of whole sets of peptides enables efficient discriminative learning of a dynamic Bayesian network for spectrum identification, leading to greatly improved spectrum identification accuracy.Contact: bilmes@uw.edu or william-noble@uw.eduSupplementary information: Supplementary data are available at Bioinformatics online.
A network-driven approach for genome-wide association mapping
Authors: Lee Seunghak , Kong Soonho , Xing Eric P. 
Published: June 2016

AbstractMotivation : It remains a challenge to detect associations between genotypes and phenotypes because of insufficient sample sizes and complex underlying mechanisms involved in associations. Fortunately, it is becoming more feasible to obtain gene expression data in addition to genotypes and phenotypes, giving us new opportunities to detect true genotype–phenotype associations while unveiling their association mechanisms.Results : In this article, we propose a novel method, NETAM, that accurately detects associations between SNPs and phenotypes, as well as gene traits involved in such associations. We take a network-driven approach: NETAM first constructs an association network, where nodes represent SNPs, gene traits or phenotypes, and edges represent the strength of association between two nodes. NETAM assigns a score to each path from an SNP to a phenotype, and then identifies significant paths based on the scores. In our simulation study, we show that NETAM finds significantly more phenotype-associated SNPs than traditional genotype–phenotype association analysis under false positive control, taking advantage of gene expression data. Furthermore, we applied NETAM on late-onset Alzheimer’s disease data and identified 477 significant path associations, among which we analyzed paths related to beta-amyloid, estrogen, and nicotine pathways. We also provide hypothetical biological pathways to explain our findings.Availability and implementation : Software is available at http://www.sailing.cs.cmu.edu/ .Contact : epxing@cs.cmu.edu