Network motif-based identification of transcription factor-target gene relationships by integrating multi-source biological data.

Abstract:

BACKGROUND:Integrating data from multiple global assays and curated databases is essential to understand the spatio-temporal interactions within cells. Different experiments measure cellular processes at various widths and depths, while databases contain biological information based on established facts or published data. Integrating these complementary datasets helps infer a mutually consistent transcriptional regulatory network (TRN) with strong similarity to the structure of the underlying genetic regulatory modules. Decomposing the TRN into a small set of recurring regulatory patterns, called network motifs (NM), facilitates the inference. Identifying NMs defined by specific transcription factors (TF) establishes the framework structure of a TRN and allows the inference of TF-target gene relationship. This paper introduces a computational framework for utilizing data from multiple sources to infer TF-target gene relationships on the basis of NMs. The data include time course gene expression profiles, genome-wide location analysis data, binding sequence data, and gene ontology (GO) information. RESULTS:The proposed computational framework was tested using gene expression data associated with cell cycle progression in yeast. Among 800 cell cycle related genes, 85 were identified as candidate TFs and classified into four previously defined NMs. The NMs for a subset of TFs are obtained from literature. Support vector machine (SVM) classifiers were used to estimate NMs for the remaining TFs. The potential downstream target genes for the TFs were clustered into 34 biologically significant groups. The relationships between TFs and potential target gene clusters were examined by training recurrent neural networks whose topologies mimic the NMs to which the TFs are classified. The identified relationships between TFs and gene clusters were evaluated using the following biological validation and statistical analyses: (1) Gene set enrichment analysis (GSEA) to evaluate the clustering results; (2) Leave-one-out cross-validation (LOOCV) to ensure that the SVM classifiers assign TFs to NM categories with high confidence; (3) Binding site enrichment analysis (BSEA) to determine enrichment of the gene clusters for the cognate binding sites of their predicted TFs; (4) Comparison with previously reported results in the literatures to confirm the inferred regulations. CONCLUSION:The major contribution of this study is the development of a computational framework to assist the inference of TRN by integrating heterogeneous data from multiple sources and by decomposing a TRN into NM-based modules. The inference capability of the proposed framework is verified statistically (e.g., LOOCV) and biologically (e.g., GSEA, BSEA, and literature validation). The proposed framework is useful for inferring small NM-based modules of TF-target gene relationships that can serve as a basis for generating new testable hypotheses.

journal_name

BMC Bioinformatics

journal_title

BMC bioinformatics

authors

Zhang Y,Xuan J,de los Reyes BG,Clarke R,Ressom HW

doi

10.1186/1471-2105-9-203

subject

Has Abstract

pub_date

2008-04-21 00:00:00

pages

203

issn

1471-2105

pii

1471-2105-9-203

journal_volume

9

pub_type

杂志文章
  • Image-based classification of plant genus and family for trained and untrained plant species.

    abstract:BACKGROUND:Modern plant taxonomy reflects phylogenetic relationships among taxa based on proposed morphological and genetic similarities. However, taxonomical relation is not necessarily reflected by close overall resemblance, but rather by commonality of very specific morphological characters or similarity on the mole...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-018-2474-x

    authors: Seeland M,Rzanny M,Boho D,Wäldchen J,Mäder P

    更新日期:2019-01-03 00:00:00

  • A preliminary PET radiomics study of brain metastases using a fully automatic segmentation method.

    abstract:BACKGROUND:Positron Emission Tomography (PET) is increasingly utilized in radiomics studies for treatment evaluation purposes. Nevertheless, lesion volume identification in PET images is a critical and still challenging step in the process of radiomics, due to the low spatial resolution and high noise level of PET imag...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-020-03647-7

    authors: Stefano A,Comelli A,Bravatà V,Barone S,Daskalovski I,Savoca G,Sabini MG,Ippolito M,Russo G

    更新日期:2020-09-16 00:00:00

  • A benchmark study of sequence alignment methods for protein clustering.

    abstract:BACKGROUND:Protein sequence alignment analyses have become a crucial step for many bioinformatics studies during the past decades. Multiple sequence alignment (MSA) and pair-wise sequence alignment (PSA) are two major approaches in sequence alignment. Former benchmark studies revealed drawbacks of MSA methods on nucleo...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-018-2524-4

    authors: Wang Y,Wu H,Cai Y

    更新日期:2018-12-31 00:00:00

  • Compartmentalization of the Edinburgh Human Metabolic Network.

    abstract:BACKGROUND:Direct in vivo investigation of human metabolism is complicated by the distinct metabolic functions of various sub-cellular organelles. Diverse micro-environments in different organelles may lead to distinct functions of the same protein and the use of different enzymes for the same metabolic reaction. To be...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-11-393

    authors: Hao T,Ma HW,Zhao XM,Goryanin I

    更新日期:2010-07-22 00:00:00

  • iMEGES: integrated mental-disorder GEnome score by deep neural network for prioritizing the susceptibility genes for mental disorders in personal genomes.

    abstract:BACKGROUND:A range of rare and common genetic variants have been discovered to be potentially associated with mental diseases, but many more have not been uncovered. Powerful integrative methods are needed to systematically prioritize both variants and genes that confer susceptibility to mental diseases in personal gen...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-018-2469-7

    authors: Khan A,Liu Q,Wang K

    更新日期:2018-12-28 00:00:00

  • Probe-level linear model fitting and mixture modeling results in high accuracy detection of differential gene expression.

    abstract:BACKGROUND:The identification of differentially expressed genes (DEGs) from Affymetrix GeneChips arrays is currently done by first computing expression levels from the low-level probe intensities, then deriving significance by comparing these expression levels between conditions. The proposed PL-LM (Probe-Level Linear ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-7-391

    authors: Lemieux S

    更新日期:2006-08-25 00:00:00

  • DLAD4U: deriving and prioritizing disease lists from PubMed literature.

    abstract:BACKGROUND:Due to recent technology advancements, disease related knowledge is growing rapidly. It becomes nontrivial to go through all published literature to identify associations between human diseases and genetic, environmental, and life style factors, disease symptoms, and treatment strategies. Here we report DLAD...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-018-2463-0

    authors: Shen J,Vasaikar S,Zhang B

    更新日期:2018-12-28 00:00:00

  • GenNon-h: generating multiple sequence alignments on nonhomogeneous phylogenetic trees.

    abstract:BACKGROUND:A number of software packages are available to generate DNA multiple sequence alignments (MSAs) evolved under continuous-time Markov processes on phylogenetic trees. On the other hand, methods of simulating the DNA MSA directly from the transition matrices do not exist. Moreover, existing software restricts ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-13-216

    authors: Kedzierska AM,Casanellas M

    更新日期:2012-08-28 00:00:00

  • Components of the antigen processing and presentation pathway revealed by gene expression microarray analysis following B cell antigen receptor (BCR) stimulation.

    abstract:BACKGROUND:Activation of naïve B lymphocytes by extracellular ligands, e.g. antigen, lipopolysaccharide (LPS) and CD40 ligand, induces a combination of common and ligand-specific phenotypic changes through complex signal transduction pathways. For example, although all three of these ligands induce proliferation, only ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-7-237

    authors: Lee JA,Sinkovits RS,Mock D,Rab EL,Cai J,Yang P,Saunders B,Hsueh RC,Choi S,Subramaniam S,Scheuermann RH,Alliance for Cellular Signaling.

    更新日期:2006-05-02 00:00:00

  • Measuring similarities between transcription factor binding sites.

    abstract:BACKGROUND:Collections of transcription factor binding profiles (Transfac, Jaspar) are essential to identify regulatory elements in DNA sequences. Subsets of highly similar profiles complicate large scale analysis of transcription factor binding sites. RESULTS:We propose to identify and group similar profiles using tw...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-6-237

    authors: Kielbasa SM,Gonze D,Herzel H

    更新日期:2005-09-28 00:00:00

  • OpWise: operons aid the identification of differentially expressed genes in bacterial microarray experiments.

    abstract:BACKGROUND:Differentially expressed genes are typically identified by analyzing the variation between replicate measurements. These procedures implicitly assume that there are no systematic errors in the data even though several sources of systematic error are known. RESULTS:OpWise estimates the amount of systematic e...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-7-19

    authors: Price MN,Arkin AP,Alm EJ

    更新日期:2006-01-13 00:00:00

  • MATLIGN: a motif clustering, comparison and matching tool.

    abstract:BACKGROUND:Sequence motifs representing transcription factor binding sites (TFBS) are commonly encoded as position frequency matrices (PFM) or degenerate consensus sequences (CS). These formats are used to represent the characterised TFBS profiles stored in transcription factor databases, as well as to represent the po...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-8-189

    authors: Kankainen M,Löytynoja A

    更新日期:2007-06-08 00:00:00

  • Ontological representation, integration, and analysis of LINCS cell line cells and their cellular responses.

    abstract:BACKGROUND:Aiming to understand cellular responses to different perturbations, the NIH Common Fund Library of Integrated Network-based Cellular Signatures (LINCS) program involves many institutes and laboratories working on over a thousand cell lines. The community-based Cell Line Ontology (CLO) is selected as the defa...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-017-1981-5

    authors: Ong E,Xie J,Ni Z,Liu Q,Sarntivijai S,Lin Y,Cooper D,Terryn R,Stathias V,Chung C,Schürer S,He Y

    更新日期:2017-12-21 00:00:00

  • Predicting variant deleteriousness in non-human species: applying the CADD approach in mouse.

    abstract:BACKGROUND:Predicting the deleteriousness of observed genomic variants has taken a step forward with the introduction of the Combined Annotation Dependent Depletion (CADD) approach, which trains a classifier on the wealth of available human genomic information. This raises the question whether it can be done with less ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-018-2337-5

    authors: Groß C,de Ridder D,Reinders M

    更新日期:2018-10-12 00:00:00

  • Gene set enrichment meta-learning analysis: next- generation sequencing versus microarrays.

    abstract:BACKGROUND:Reproducibility of results can have a significant impact on the acceptance of new technologies in gene expression analysis. With the recent introduction of the so-called next-generation sequencing (NGS) technology and established microarrays, one is able to choose between two completely different platforms f...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-11-176

    authors: Stiglic G,Bajgot M,Kokol P

    更新日期:2010-04-08 00:00:00

  • GOmotif: A web server for investigating the biological role of protein sequence motifs.

    abstract:BACKGROUND:Many proteins contain conserved sequence patterns (motifs) that contribute to their functionality. The process of experimentally identifying and validating novel protein motifs can be difficult, expensive, and time consuming. A means for helping to identify in advance the possible function of a novel motif i...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-12-379

    authors: Bristow F,He R,Van Domselaar G

    更新日期:2011-09-26 00:00:00

  • FIGENIX: intelligent automation of genomic annotation: expertise integration in a new software platform.

    abstract:BACKGROUND:Two of the main objectives of the genomic and post-genomic era are to structurally and functionally annotate genomes which consists of detecting genes' position and structure, and inferring their function (as well as of other features of genomes). Structural and functional annotation both require the complex...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-6-198

    authors: Gouret P,Vitiello V,Balandraud N,Gilles A,Pontarotti P,Danchin EG

    更新日期:2005-08-05 00:00:00

  • NPBSS: a new PacBio sequencing simulator for generating the continuous long reads with an empirical model.

    abstract:BACKGROUND:PacBio sequencing platform offers longer read lengths than the second-generation sequencing technologies. It has revolutionized de novo genome assembly and enabled the automated reconstruction of reference-quality genomes. Due to its extremely wide range of application areas, fast sequencing simulation syste...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-018-2208-0

    authors: Wei ZG,Zhang SW

    更新日期:2018-05-22 00:00:00

  • Machine learning for discovering missing or wrong protein function annotations : A comparison using updated benchmark datasets.

    abstract:BACKGROUND:A massive amount of proteomic data is generated on a daily basis, nonetheless annotating all sequences is costly and often unfeasible. As a countermeasure, machine learning methods have been used to automatically annotate new protein functions. More specifically, many studies have investigated hierarchical m...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章,评审

    doi:10.1186/s12859-019-3060-6

    authors: Nakano FK,Lietaert M,Vens C

    更新日期:2019-09-23 00:00:00

  • Natural computation meta-heuristics for the in silico optimization of microbial strains.

    abstract:BACKGROUND:One of the greatest challenges in Metabolic Engineering is to develop quantitative models and algorithms to identify a set of genetic manipulations that will result in a microbial strain with a desirable metabolic phenotype which typically means having a high yield/productivity. This challenge is not only du...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-9-499

    authors: Rocha M,Maia P,Mendes R,Pinto JP,Ferreira EC,Nielsen J,Patil KR,Rocha I

    更新日期:2008-11-27 00:00:00

  • Approaching the taxonomic affiliation of unidentified sequences in public databases--an example from the mycorrhizal fungi.

    abstract:BACKGROUND:During the last few years, DNA sequence analysis has become one of the primary means of taxonomic identification of species, particularly so for species that are minute or otherwise lack distinct, readily obtainable morphological characters. Although the number of sequences available for comparison in public...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-6-178

    authors: Nilsson RH,Kristiansson E,Ryberg M,Larsson KH

    更新日期:2005-07-18 00:00:00

  • Reduction strategies for hierarchical multi-label classification in protein function prediction.

    abstract:BACKGROUND:Hierarchical Multi-Label Classification is a classification task where the classes to be predicted are hierarchically organized. Each instance can be assigned to classes belonging to more than one path in the hierarchy. This scenario is typically found in protein function prediction, considering that each pr...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-016-1232-1

    authors: Cerri R,Barros RC,P L F de Carvalho AC,Jin Y

    更新日期:2016-09-15 00:00:00

  • Fregene: simulation of realistic sequence-level data in populations and ascertained samples.

    abstract:BACKGROUND:FREGENE simulates sequence-level data over large genomic regions in large populations. Because, unlike coalescent simulators, it works forwards through time, it allows complex scenarios of selection, demography, and recombination to be modelled simultaneously. Detailed tracking of sites under selection is im...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-9-364

    authors: Chadeau-Hyam M,Hoggart CJ,O'Reilly PF,Whittaker JC,De Iorio M,Balding DJ

    更新日期:2008-09-08 00:00:00

  • CNN-based ranking for biomedical entity normalization.

    abstract:BACKGROUND:Most state-of-the-art biomedical entity normalization systems, such as rule-based systems, merely rely on morphological information of entity mentions, but rarely consider their semantic information. In this paper, we introduce a novel convolutional neural network (CNN) architecture that regards biomedical e...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-017-1805-7

    authors: Li H,Chen Q,Tang B,Wang X,Xu H,Wang B,Huang D

    更新日期:2017-10-03 00:00:00

  • Compromise or optimize? The breakpoint anti-median.

    abstract:BACKGROUND:The median of k≥3 genomes was originally defined to find a compromise genome indicative of a common ancestor. However, in gene order comparisons, the usual definitions based on minimizing the sum of distances to the input genomes lead to degenerate medians reflecting only one of the input genomes. "Near-medi...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-016-1340-y

    authors: Larlee CA,Brandts A,Sankoff D

    更新日期:2016-12-15 00:00:00

  • Phylotastic! Making tree-of-life knowledge accessible, reusable and convenient.

    abstract:BACKGROUND:Scientists rarely reuse expert knowledge of phylogeny, in spite of years of effort to assemble a great "Tree of Life" (ToL). A notable exception involves the use of Phylomatic, which provides tools to generate custom phylogenies from a large, pre-computed, expert phylogeny of plant taxa. This suggests great ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-14-158

    authors: Stoltzfus A,Lapp H,Matasci N,Deus H,Sidlauskas B,Zmasek CM,Vaidya G,Pontelli E,Cranston K,Vos R,Webb CO,Harmon LJ,Pirrung M,O'Meara B,Pennell MW,Mirarab S,Rosenberg MS,Balhoff JP,Bik HM,Heath TA,Midford PE,Brown

    更新日期:2013-05-13 00:00:00

  • Cascaded classifiers for confidence-based chemical named entity recognition.

    abstract:BACKGROUND:Chemical named entities represent an important facet of biomedical text. RESULTS:We have developed a system to use character-based n-grams, Maximum Entropy Markov Models and rescoring to recognise chemical names and other such entities, and to make confidence estimates for the extracted entities. An adjusta...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-9-S11-S4

    authors: Corbett P,Copestake A

    更新日期:2008-11-19 00:00:00

  • A multiobjective approach to the genetic code adaptability problem.

    abstract:BACKGROUND:The organization of the canonical code has intrigued researches since it was first described. If we consider all codes mapping the 64 codes into 20 amino acids and one stop codon, there are more than 1.51×10(84) possible genetic codes. The main question related to the organization of the genetic code is why ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-015-0480-9

    authors: de Oliveira LL,de Oliveira PS,Tinós R

    更新日期:2015-02-19 00:00:00

  • Accurate determination of node and arc multiplicities in de bruijn graphs using conditional random fields.

    abstract:BACKGROUND:De Bruijn graphs are key data structures for the analysis of next-generation sequencing data. They efficiently represent the overlap between reads and hence, also the underlying genome sequence. However, sequencing errors and repeated subsequences render the identification of the true underlying sequence dif...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-020-03740-x

    authors: Steyaert A,Audenaert P,Fostier J

    更新日期:2020-09-14 00:00:00

  • MultiLoc2: integrating phylogeny and Gene Ontology terms improves subcellular protein localization prediction.

    abstract:BACKGROUND:Knowledge of subcellular localization of proteins is crucial to proteomics, drug target discovery and systems biology since localization and biological function are highly correlated. In recent years, numerous computational prediction methods have been developed. Nevertheless, there is still a need for predi...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-10-274

    authors: Blum T,Briesemeister S,Kohlbacher O

    更新日期:2009-09-01 00:00:00