HMMvar-func: a new method for predicting the functional outcome of genetic variants.

Abstract:

BACKGROUND:Numerous tools have been developed to predict the fitness effects (i.e., neutral, deleterious, or beneficial) of genetic variants on corresponding proteins. However, prediction in terms of whether a variant causes the variant bearing protein to lose the original function or gain new function is also needed for better understanding of how the variant contributes to disease/cancer. To address this problem, the present work introduces and computationally defines four types of functional outcome of a variant: gain, loss, switch, and conservation of function. The deployment of multiple hidden Markov models is proposed to computationally classify mutations by the four functional impact types. RESULTS:The functional outcome is predicted for over a hundred thyroid stimulating hormone receptor (TSHR) mutations, as well as cancer related mutations in oncogenes or tumor suppressor genes. The results show that the proposed computational method is effective in fine grained prediction of the functional outcome of a mutation, and can be used to help elucidate the molecular mechanism of disease/cancer causing mutations. The program is freely available at http://bioinformatics.cs.vt.edu/zhanglab/HMMvar/download.php. CONCLUSION:This work is the first to computationally define and predict functional impact of mutations, loss, switch, gain, or conservation of function. These fine grained predictions can be especially useful for identifying mutations that cause or are linked to cancer.

journal_name

BMC Bioinformatics

journal_title

BMC bioinformatics

authors

Liu M,Watson LT,Zhang L

doi

10.1186/s12859-015-0781-z

subject

Has Abstract

pub_date

2015-10-30 00:00:00

pages

351

issn

1471-2105

pii

10.1186/s12859-015-0781-z

journal_volume

16

pub_type

杂志文章
  • Generating quantitative models describing the sequence specificity of biological processes with the stabilized matrix method.

    abstract:BACKGROUND:Many processes in molecular biology involve the recognition of short sequences of nucleic-or amino acids, such as the binding of immunogenic peptides to major histocompatibility complex (MHC) molecules. From experimental data, a model of the sequence specificity of these processes can be constructed, such as...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-6-132

    authors: Peters B,Sette A

    更新日期:2005-05-31 00:00:00

  • Pripper: prediction of caspase cleavage sites from whole proteomes.

    abstract:BACKGROUND:Caspases are a family of proteases that have central functions in programmed cell death (apoptosis) and inflammation. Caspases mediate their effects through aspartate-specific cleavage of their target proteins, and at present almost 400 caspase substrates are known. There are several methods developed to pre...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-11-320

    authors: Piippo M,Lietzén N,Nevalainen OS,Salmi J,Nyman TA

    更新日期:2010-06-15 00:00:00

  • Robust joint score tests in the application of DNA methylation data analysis.

    abstract:BACKGROUND:Recently differential variability has been showed to be valuable in evaluating the association of DNA methylation to the risks of complex human diseases. The statistical tests based on both differential methylation level and differential variability can be more powerful than those based only on differential ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-018-2185-3

    authors: Li X,Fu Y,Wang X,Qiu W

    更新日期:2018-05-18 00:00:00

  • An evaluation of copy number variation detection tools for cancer using whole exome sequencing data.

    abstract:BACKGROUND:Recently copy number variation (CNV) has gained considerable interest as a type of genomic/genetic variation that plays an important role in disease susceptibility. Advances in sequencing technology have created an opportunity for detecting CNVs more accurately. Recently whole exome sequencing (WES) has beco...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-017-1705-x

    authors: Zare F,Dow M,Monteleone N,Hosny A,Nabavi S

    更新日期:2017-05-31 00:00:00

  • Shared data science infrastructure for genomics data.

    abstract:BACKGROUND:Creating a scalable computational infrastructure to analyze the wealth of information contained in data repositories is difficult due to significant barriers in organizing, extracting and analyzing relevant data. Shared data science infrastructures like Boag is needed to efficiently process and parse data co...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-019-2967-2

    authors: Bagheri H,Muppirala U,Masonbrink RE,Severin AJ,Rajan H

    更新日期:2019-08-22 00:00:00

  • OmicsARules: a R package for integration of multi-omics datasets via association rules mining.

    abstract:BACKGROUND:The improvements of high throughput technologies have produced large amounts of multi-omics experiments datasets. Initial analysis of these data has revealed many concurrent gene alterations within single dataset or/and among multiple omics datasets. Although powerful bioinformatics pipelines have been devel...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-019-3171-0

    authors: Chen D,Zhang F,Zhao Q,Xu J

    更新日期:2019-11-08 00:00:00

  • Latent Semantic Indexing of PubMed abstracts for identification of transcription factor candidates from microarray derived gene sets.

    abstract:BACKGROUND:Identification of transcription factors (TFs) responsible for modulation of differentially expressed genes is a key step in deducing gene regulatory pathways. Most current methods identify TFs by searching for presence of DNA binding motifs in the promoter regions of co-regulated genes. However, this strateg...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-12-S10-S19

    authors: Roy S,Heinrich K,Phan V,Berry MW,Homayouni R

    更新日期:2011-10-18 00:00:00

  • Systematic identification of functional modules and cis-regulatory elements in Arabidopsis thaliana.

    abstract:BACKGROUND:Several large-scale gene co-expression networks have been constructed successfully for predicting gene functional modules and cis-regulatory elements in Arabidopsis (Arabidopsis thaliana). However, these networks are usually constructed and analyzed in an ad hoc manner. In this study, we propose a completely...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-12-S12-S2

    authors: Ruan J,Perez J,Hernandez B,Lei C,Sunter G,Sponsel VM

    更新日期:2011-11-24 00:00:00

  • Advances in translational bioinformatics facilitate revealing the landscape of complex disease mechanisms.

    abstract::Advances of high-throughput technologies have rapidly produced more and more data from DNAs and RNAs to proteins, especially large volumes of genome-scale data. However, connection of the genomic information to cellular functions and biological behaviours relies on the development of effective approaches at higher sys...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-15-S17-I1

    authors: Yang JY,Dunker A,Liu JS,Qin X,Arabnia HR,Yang W,Niemierko A,Chen Z,Luo Z,Wang L,Liu Y,Xu D,Deng Y,Tong W,Yang M

    更新日期:2014-01-01 00:00:00

  • SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool.

    abstract:BACKGROUND:It has long been recognized that sensitivity analysis plays a key role in modeling and analyzing cellular and biochemical processes. Systems biology markup language (SBML) has become a well-known platform for coding and sharing mathematical models of such processes. However, current SBML compatible software ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-9-342

    authors: Zi Z,Zheng Y,Rundell AE,Klipp E

    更新日期:2008-08-15 00:00:00

  • Inferring the role of transcription factors in regulatory networks.

    abstract:BACKGROUND:Expression profiles obtained from multiple perturbation experiments are increasingly used to reconstruct transcriptional regulatory networks, from well studied, simple organisms up to higher eukaryotes. Admittedly, a key ingredient in developing a reconstruction method is its ability to integrate heterogeneo...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-9-228

    authors: Veber P,Guziolowski C,Le Borgne M,Radulescu O,Siegel A

    更新日期:2008-05-06 00:00:00

  • Detection of copy number variation from array intensity and sequencing read depth using a stepwise Bayesian model.

    abstract:BACKGROUND:Copy number variants (CNVs) have been demonstrated to occur at a high frequency and are now widely believed to make a significant contribution to the phenotypic variation in human populations. Array-based comparative genomic hybridization (array-CGH) and newly developed read-depth approach through ultrahigh ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-11-539

    authors: Zhang ZD,Gerstein MB

    更新日期:2010-10-31 00:00:00

  • OmniMapFree: a unified tool to visualise and explore sequenced genomes.

    abstract:UNLABELLED: BACKGROUND:Acquiring and exploring whole genome sequence information for a species under investigation is now a routine experimental approach. On most genome browsers, typically, only the DNA sequence, EST support, motif search results, and GO annotations are displayed. However, for many species, a growing...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-12-447

    authors: Antoniw J,Beacham AM,Baldwin TK,Urban M,Rudd JJ,Hammond-Kosack KE

    更新日期:2011-11-15 00:00:00

  • A novel computational strategy for DNA methylation imputation using mixture regression model (MRM).

    abstract:BACKGROUND:DNA methylation is an important heritable epigenetic mark that plays a crucial role in transcriptional regulation and the pathogenesis of various human disorders. The commonly used DNA methylation measurement approaches, e.g., Illumina Infinium HumanMethylation-27 and -450 BeadChip arrays (27 K and 450 K arr...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-020-03865-z

    authors: Yu F,Xu C,Deng HW,Shen H

    更新日期:2020-12-01 00:00:00

  • SHIVA - a web application for drug resistance and tropism testing in HIV.

    abstract:BACKGROUND:Drug resistance testing is mandatory in antiretroviral therapy in human immunodeficiency virus (HIV) infected patients for successful treatment. The emergence of resistances against antiretroviral agents remains the major obstacle in inhibition of viral replication and thus to control infection. Due to the h...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-016-1179-2

    authors: Riemenschneider M,Hummel T,Heider D

    更新日期:2016-08-22 00:00:00

  • A method of predicting changes in human gene splicing induced by genetic variants in context of cis-acting elements.

    abstract:BACKGROUND:Polymorphic variants and mutations disrupting canonical splicing isoforms are among the leading causes of human hereditary disorders. While there is a substantial evidence of aberrant splicing causing Mendelian diseases, the implication of such events in multi-genic disorders is yet to be well understood. We...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-11-22

    authors: Churbanov A,Vorechovský I,Hicks C

    更新日期:2010-01-12 00:00:00

  • Efficient prediction of human protein-protein interactions at a global scale.

    abstract:BACKGROUND:Our knowledge of global protein-protein interaction (PPI) networks in complex organisms such as humans is hindered by technical limitations of current methods. RESULTS:On the basis of short co-occurring polypeptide regions, we developed a tool called MP-PIPE capable of predicting a global human PPI network ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-014-0383-1

    authors: Schoenrock A,Samanfar B,Pitre S,Hooshyar M,Jin K,Phillips CA,Wang H,Phanse S,Omidi K,Gui Y,Alamgir M,Wong A,Barrenäs F,Babu M,Benson M,Langston MA,Green JR,Dehne F,Golshani A

    更新日期:2014-12-10 00:00:00

  • Comparing the performance of selected variant callers using synthetic data and genome segmentation.

    abstract:BACKGROUND:High-throughput sequencing has rapidly become an essential part of precision cancer medicine. But validating results obtained from analyzing and interpreting genomic data remains a rate-limiting factor. The gold standard, of course, remains manual validation by expert panels, which is not without its weaknes...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-018-2440-7

    authors: Bian X,Zhu B,Wang M,Hu Y,Chen Q,Nguyen C,Hicks B,Meerzaman D

    更新日期:2018-11-19 00:00:00

  • Extracting transcription factor binding sites from unaligned gene sequences with statistical models.

    abstract:BACKGROUND:Transcription factor binding sites (TFBSs) are crucial in the regulation of gene transcription. Recently, chromatin immunoprecipitation followed by cDNA microarray hybridization (ChIP-chip array) has been used to identify potential regulatory sequences, but the procedure can only map the probable protein-DNA...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-9-S12-S7

    authors: Lu CC,Yuan WH,Chen TM

    更新日期:2008-12-12 00:00:00

  • Colony size measurement of the yeast gene deletion strains for functional genomics.

    abstract:BACKGROUND:Numerous functional genomics approaches have been developed to study the model organism yeast, Saccharomyces cerevisiae, with the aim of systematically understanding the biology of the cell. Some of these techniques are based on yeast growth differences under different conditions, such as those generated by ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-8-117

    authors: Memarian N,Jessulat M,Alirezaie J,Mir-Rashed N,Xu J,Zareie M,Smith M,Golshani A

    更新日期:2007-04-04 00:00:00

  • A fast indexing approach for protein structure comparison.

    abstract:BACKGROUND:Protein structure comparison is a fundamental task in structural biology. While the number of known protein structures has grown rapidly over the last decade, searching a large database of protein structures is still relatively slow using existing methods. There is a need for new techniques which can rapidly...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-11-S1-S46

    authors: Zhang L,Bailey J,Konagurthu AS,Ramamohanarao K

    更新日期:2010-01-18 00:00:00

  • Detection of nuclei in 4D Nomarski DIC microscope images of early Caenorhabditis elegans embryos using local image entropy and object tracking.

    abstract:BACKGROUND:The ability to detect nuclei in embryos is essential for studying the development of multicellular organisms. A system of automated nuclear detection has already been tested on a set of four-dimensional (4D) Nomarski differential interference contrast (DIC) microscope images of Caenorhabditis elegans embryos...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-6-125

    authors: Hamahashi S,Onami S,Kitano H

    更新日期:2005-05-24 00:00:00

  • Predikin and PredikinDB: a computational framework for the prediction of protein kinase peptide specificity and an associated database of phosphorylation sites.

    abstract:BACKGROUND:We have previously described an approach to predicting the substrate specificity of serine-threonine protein kinases. The method, named Predikin, identifies key conserved substrate-determining residues in the kinase catalytic domain that contact the substrate in the region of the phosphorylation site and so ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-9-245

    authors: Saunders NF,Brinkworth RI,Huber T,Kemp BE,Kobe B

    更新日期:2008-05-26 00:00:00

  • Intestinal microbiota domination under extreme selective pressures characterized by metagenomic read cloud sequencing and assembly.

    abstract:BACKGROUND:Low diversity of the gut microbiome, often progressing to the point of intestinal domination by a single species, has been linked to poor outcomes in patients undergoing hematopoietic cell transplantation (HCT). Our ability to understand how certain organisms attain intestinal domination over others has been...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-019-3073-1

    authors: Kang JB,Siranosian BA,Moss EL,Banaei N,Andermann TM,Bhatt AS

    更新日期:2019-12-02 00:00:00

  • Asymmetric bagging and feature selection for activities prediction of drug molecules.

    abstract:BACKGROUND:Activities of drug molecules can be predicted by QSAR (quantitative structure activity relationship) models, which overcomes the disadvantages of high cost and long cycle by employing the traditional experimental method. With the fact that the number of drug molecules with positive activity is rather fewer t...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-9-S6-S7

    authors: Li GZ,Meng HH,Lu WC,Yang JY,Yang MQ

    更新日期:2008-05-28 00:00:00

  • PESM: predicting the essentiality of miRNAs based on gradient boosting machines and sequences.

    abstract:BACKGROUND:MicroRNAs (miRNAs) are a kind of small noncoding RNA molecules that are direct posttranscriptional regulations of mRNA targets. Studies have indicated that miRNAs play key roles in complex diseases by taking part in many biological processes, such as cell growth, cell death and so on. Therefore, in order to ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-020-3426-9

    authors: Yan C,Wu FX,Wang J,Duan G

    更新日期:2020-03-18 00:00:00

  • Analysis and prediction of antibacterial peptides.

    abstract:BACKGROUND:Antibacterial peptides are important components of the innate immune system, used by the host to protect itself from different types of pathogenic bacteria. Over the last few decades, the search for new drugs and drug targets has prompted an interest in these antibacterial peptides. We analyzed 486 antibacte...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-8-263

    authors: Lata S,Sharma BK,Raghava GP

    更新日期:2007-07-23 00:00:00

  • Discovering motifs that induce sequencing errors.

    abstract:BACKGROUND:Elevated sequencing error rates are the most predominant obstacle in single-nucleotide polymorphism (SNP) detection, which is a major goal in the bulk of current studies using next-generation sequencing (NGS). Beyond routinely handled generic sources of errors, certain base calling errors relate to specific ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-14-S5-S1

    authors: Allhoff M,Schönhuth A,Martin M,Costa IG,Rahmann S,Marschall T

    更新日期:2013-01-01 00:00:00

  • Visualising very large phylogenetic trees in three dimensional hyperbolic space.

    abstract:BACKGROUND:Common existing phylogenetic tree visualisation tools are not able to display readable trees with more than a few thousand nodes. These existing methodologies are based in two dimensional space. RESULTS:We introduce the idea of visualising phylogenetic trees in three dimensional hyperbolic space with the Wa...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-5-48

    authors: Hughes T,Hyun Y,Liberles DA

    更新日期:2004-04-29 00:00:00

  • Structural alignment of protein descriptors - a combinatorial model.

    abstract:BACKGROUND:Structural alignment of proteins is one of the most challenging problems in molecular biology. The tertiary structure of a protein strictly correlates with its function and computationally predicted structures are nowadays a main premise for understanding the latter. However, computationally derived 3D model...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-016-1237-9

    authors: Antczak M,Kasprzak M,Lukasiak P,Blazewicz J

    更新日期:2016-09-17 00:00:00