Simulating autosomal genotypes with realistic linkage disequilibrium and a spiked-in genetic effect.

Abstract:

BACKGROUND:To evaluate statistical methods for genome-wide genetic analyses, one needs to be able to simulate realistic genotypes. We here describe a method, applicable to a broad range of association study designs, that can simulate autosome-wide single-nucleotide polymorphism data with realistic linkage disequilibrium and with spiked in, user-specified, single or multi-SNP causal effects. RESULTS:Our construction uses existing genome-wide association data from unrelated case-parent triads, augmented by including a hypothetical complement triad for each triad (same parents but with a hypothetical offspring who carries the non-transmitted parental alleles). We assign offspring qualitative or quantitative traits probabilistically through a specified risk model and show that our approach destroys the risk signals from the original data. Our method can simulate genetically homogeneous or stratified populations and can simulate case-parents studies, case-control studies, case-only studies, or studies of quantitative traits. We show that allele frequencies and linkage disequilibrium structure in the original genome-wide association sample are preserved in the simulated data. We have implemented our method in an R package (TriadSim) which is freely available at the comprehensive R archive network. CONCLUSION:We have proposed a method for simulating genome-wide SNP data with realistic linkage disequilibrium. Our method will be useful for developing statistical methods for studying genetic associations, including higher order effects like epistasis and gene by environment interactions.

journal_name

BMC Bioinformatics

journal_title

BMC bioinformatics

authors

Shi M,Umbach DM,Wise AS,Weinberg CR

doi

10.1186/s12859-017-2004-2

subject

Has Abstract

pub_date

2018-01-02 00:00:00

pages

2

issue

1

issn

1471-2105

pii

10.1186/s12859-017-2004-2

journal_volume

19

pub_type

杂志文章
  • Bayesian detection of periodic mRNA time profiles without use of training examples.

    abstract:BACKGROUND:Detection of periodically expressed genes from microarray data without use of known periodic and non-periodic training examples is an important problem, e.g. for identifying genes regulated by the cell-cycle in poorly characterised organisms. Commonly the investigator is only interested in genes expressed at...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-7-63

    authors: Andersson CR,Isaksson A,Gustafsson MG

    更新日期:2006-02-09 00:00:00

  • Towards mainstreaming of biodiversity data publishing: recommendations of the GBIF Data Publishing Framework Task Group.

    abstract:BACKGROUND:Data are the evidentiary basis for scientific hypotheses, analyses and publication, for policy formation and for decision-making. They are essential to the evaluation and testing of results by peer scientists both present and future. There is broad consensus in the scientific and conservation communities tha...

    journal_title:BMC bioinformatics

    pub_type: 指南,杂志文章

    doi:10.1186/1471-2105-12-S15-S1

    authors: Moritz T,Krishnan S,Roberts D,Ingwersen P,Agosti D,Penev L,Cockerill M,Chavan V,Data Publishing Framework Task Group.

    更新日期:2011-01-01 00:00:00

  • dupRadar: a Bioconductor package for the assessment of PCR artifacts in RNA-Seq data.

    abstract:BACKGROUND:PCR clonal artefacts originating from NGS library preparation can affect both genomic as well as RNA-Seq applications when protocols are pushed to their limits. In RNA-Seq however the artifactual reads are not easy to tell apart from normal read duplication due to natural over-sequencing of highly expressed ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-016-1276-2

    authors: Sayols S,Scherzinger D,Klein H

    更新日期:2016-10-21 00:00:00

  • WellInverter: a web application for the analysis of fluorescent reporter gene data.

    abstract:BACKGROUND:Fluorescent reporter genes have become widely used for monitoring gene expression in living cells. When a microbial strain carrying a reporter gene is grown in a microplate reader, the fluorescence and the absorbance (optical density) of the culture can be automatically measured every few minutes in a highly...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-019-2920-4

    authors: Martin Y,Page M,Blanchet C,de Jong H

    更新日期:2019-06-11 00:00:00

  • A semi-supervised learning approach to predict synthetic genetic interactions by combining functional and topological properties of functional gene network.

    abstract:BACKGROUND:Genetic interaction profiles are highly informative and helpful for understanding the functional linkages between genes, and therefore have been extensively exploited for annotating gene functions and dissecting specific pathway structures. However, our understanding is rather limited to the relationship bet...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-11-343

    authors: You ZH,Yin Z,Han K,Huang DS,Zhou X

    更新日期:2010-06-24 00:00:00

  • A database of phylogenetically atypical genes in archaeal and bacterial genomes, identified using the DarkHorse algorithm.

    abstract:BACKGROUND:The process of horizontal gene transfer (HGT) is believed to be widespread in Bacteria and Archaea, but little comparative data is available addressing its occurrence in complete microbial genomes. Collection of high-quality, automated HGT prediction data based on phylogenetic evidence has previously been im...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-9-419

    authors: Podell S,Gaasterland T,Allen EE

    更新日期:2008-10-07 00:00:00

  • Quantitative prediction of the effect of genetic variation using hidden Markov models.

    abstract:BACKGROUND:With the development of sequencing technologies, more and more sequence variants are available for investigation. Different classes of variants in the human genome have been identified, including single nucleotide substitutions, insertion and deletion, and large structural variations such as duplications and...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-15-5

    authors: Liu M,Watson LT,Zhang L

    更新日期:2014-01-09 00:00:00

  • Integrated olfactory receptor and microarray gene expression databases.

    abstract:BACKGROUND:Gene expression patterns of olfactory receptors (ORs) are an important component of the signal encoding mechanism in the olfactory system since they determine the interactions between odorant ligands and sensory neurons. We have developed the Olfactory Receptor Microarray Database (ORMD) to house OR gene exp...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-8-231

    authors: Liu N,Crasto CJ,Ma M

    更新日期:2007-06-30 00:00:00

  • An SVD-based comparison of nine whole eukaryotic genomes supports a coelomate rather than ecdysozoan lineage.

    abstract:BACKGROUND:Eukaryotic whole genome sequences are accumulating at an impressive rate. Effective methods for comparing multiple whole eukaryotic genomes on a large scale are needed. Most attempted solutions involve the production of large scale alignments, and many of these require a high stringency pre-screen for putati...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-5-204

    authors: Stuart GW,Berry MW

    更新日期:2004-12-17 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

  • Assessment of k-mer spectrum applicability for metagenomic dissimilarity analysis.

    abstract:BACKGROUND:A rapidly increasing flow of genomic data requires the development of efficient methods for obtaining its compact representation. Feature extraction facilitates classification, clustering and model analysis for testing and refining biological hypotheses. "Shotgun" metagenome is an analytically challenging ty...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-015-0875-7

    authors: Dubinkina VB,Ischenko DS,Ulyantsev VI,Tyakht AV,Alexeev DG

    更新日期:2016-01-16 00:00:00

  • Application of protein structure alignments to iterated hidden Markov model protocols for structure prediction.

    abstract:BACKGROUND:One of the most powerful methods for the prediction of protein structure from sequence information alone is the iterative construction of profile-type models. Because profiles are built from sequence alignments, the sequences included in the alignment and the method used to align them will be important to th...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-7-410

    authors: Scheeff ED,Bourne PE

    更新日期:2006-09-14 00:00:00

  • Towards a supervised classification of neocortical interneuron morphologies.

    abstract:BACKGROUND:The challenge of classifying cortical interneurons is yet to be solved. Data-driven classification into established morphological types may provide insight and practical value. RESULTS:We trained models using 217 high-quality morphologies of rat somatosensory neocortex interneurons reconstructed by a single...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-018-2470-1

    authors: Mihaljević B,Larrañaga P,Benavides-Piccione R,Hill S,DeFelipe J,Bielza C

    更新日期:2018-12-17 00:00:00

  • Identification of consensus RNA secondary structures using suffix arrays.

    abstract:BACKGROUND:The identification of a consensus RNA motif often consists in finding a conserved secondary structure with minimum free energy in an ensemble of aligned sequences. However, an alignment is often difficult to obtain without prior structural information. Thus the need for tools to automate this process. RESUL...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-7-244

    authors: Anwar M,Nguyen T,Turcotte M

    更新日期:2006-05-05 00:00:00

  • LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage.

    abstract:BACKGROUND:Cartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/β-catenin pathway plays a role in the pathogenesis of cartilage damage. In addition, it is experimentally ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-019-2981-4

    authors: Zhou W,He X,Chen Z,Fan D,Wang Y,Feng H,Zhang G,Lu A,Xiao L

    更新日期:2019-07-31 00:00:00

  • Reordering based integrative expression profiling for microarray classification.

    abstract:BACKGROUND:Current network-based microarray analysis uses the information of interactions among concerned genes/gene products, but still considers each gene expression individually. We propose an organized knowledge-supervised approach - Integrative eXpression Profiling (IXP), to improve microarray classification accur...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-13-S2-S1

    authors: Wu X,Huang H,Sonachalam M,Reinhard S,Shen J,Pandey R,Chen JY

    更新日期:2012-03-13 00:00:00

  • BISR-RNAseq: an efficient and scalable RNAseq analysis workflow with interactive report generation.

    abstract:BACKGROUND:RNA sequencing has become an increasingly affordable way to profile gene expression patterns. Here we introduce a workflow implementing several open-source softwares that can be run on a high performance computing environment. RESULTS:Developed as a tool by the Bioinformatics Shared Resource Group (BISR) at...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-019-3251-1

    authors: Gadepalli VS,Ozer HG,Yilmaz AS,Pietrzak M,Webb A

    更新日期:2019-12-20 00:00:00

  • Parameterizing sequence alignment with an explicit evolutionary model.

    abstract:BACKGROUND:Inference of sequence homology is inherently an evolutionary question, dependent upon evolutionary divergence. However, the insertion and deletion penalties in the most widely used methods for inferring homology by sequence alignment, including BLAST and profile hidden Markov models (profile HMMs), are not b...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-015-0832-5

    authors: Rivas E,Eddy SR

    更新日期:2015-12-10 00:00:00

  • Hierarchical modularity of nested bow-ties in metabolic networks.

    abstract:BACKGROUND:The exploration of the structural topology and the organizing principles of genome-based large-scale metabolic networks is essential for studying possible relations between structure and functionality of metabolic networks. Topological analysis of graph models has often been applied to study the structural c...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-7-386

    authors: Zhao J,Yu H,Luo JH,Cao ZW,Li YX

    更新日期:2006-08-18 00:00:00

  • SemaTyP: a knowledge graph based literature mining method for drug discovery.

    abstract:BACKGROUND:Drug discovery is the process through which potential new medicines are identified. High-throughput screening and computer-aided drug discovery/design are the two main drug discovery methods for now, which have successfully discovered a series of drugs. However, development of new drugs is still an extremely...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-018-2167-5

    authors: Sang S,Yang Z,Wang L,Liu X,Lin H,Wang J

    更新日期:2018-05-30 00:00:00

  • Overview of the Cancer Genetics and Pathway Curation tasks of BioNLP Shared Task 2013.

    abstract:BACKGROUND:Since their introduction in 2009, the BioNLP Shared Task events have been instrumental in advancing the development of methods and resources for the automatic extraction of information from the biomedical literature. In this paper, we present the Cancer Genetics (CG) and Pathway Curation (PC) tasks, two even...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-16-S10-S2

    authors: Pyysalo S,Ohta T,Rak R,Rowley A,Chun HW,Jung SJ,Choi SP,Tsujii J,Ananiadou S

    更新日期:2015-01-01 00:00:00

  • TreeDyn: towards dynamic graphics and annotations for analyses of trees.

    abstract:BACKGROUND:Analyses of biomolecules for biodiversity, phylogeny or structure/function studies often use graphical tree representations. Many powerful tree editors are now available, but existing tree visualization tools make little use of meta-information related to the entities under study such as taxonomic descriptio...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-7-439

    authors: Chevenet F,Brun C,Bañuls AL,Jacq B,Christen R

    更新日期:2006-10-10 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

  • ImmunoGlobe: enabling systems immunology with a manually curated intercellular immune interaction network.

    abstract:BACKGROUND:While technological advances have made it possible to profile the immune system at high resolution, translating high-throughput data into knowledge of immune mechanisms has been challenged by the complexity of the interactions underlying immune processes. Tools to explore the immune network are critical for ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-020-03702-3

    authors: Atallah MB,Tandon V,Hiam KJ,Boyce H,Hori M,Atallah W,Spitzer MH,Engleman E,Mallick P

    更新日期:2020-08-10 00:00:00

  • KRLMM: an adaptive genotype calling method for common and low frequency variants.

    abstract:BACKGROUND:SNP genotyping microarrays have revolutionized the study of complex disease. The current range of commercially available genotyping products contain extensive catalogues of low frequency and rare variants. Existing SNP calling algorithms have difficulty dealing with these low frequency variants, as the under...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-15-158

    authors: Liu R,Dai Z,Yeager M,Irizarry RA,Ritchie ME

    更新日期:2014-05-23 00:00:00

  • Predicting peptide presentation by major histocompatibility complex class I: an improved machine learning approach to the immunopeptidome.

    abstract:BACKGROUND:To further our understanding of immunopeptidomics, improved tools are needed to identify peptides presented by major histocompatibility complex class I (MHC-I). Many existing tools are limited by their reliance upon chemical affinity data, which is less biologically relevant than sampling by mass spectrometr...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-018-2561-z

    authors: Boehm KM,Bhinder B,Raja VJ,Dephoure N,Elemento O

    更新日期:2019-01-05 00:00:00

  • ICEKAT: an interactive online tool for calculating initial rates from continuous enzyme kinetic traces.

    abstract:BACKGROUND:Continuous enzyme kinetic assays are often used in high-throughput applications, as they allow rapid acquisition of large amounts of kinetic data and increased confidence compared to discontinuous assays. However, data analysis is often rate-limiting in high-throughput enzyme assays, as manual inspection and...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-020-3513-y

    authors: Olp MD,Kalous KS,Smith BC

    更新日期:2020-05-14 00:00:00

  • Sequence-based identification of recombination spots using pseudo nucleic acid representation and recursive feature extraction by linear kernel SVM.

    abstract:BACKGROUND:Identification of the recombination hot/cold spots is critical for understanding the mechanism of recombination as well as the genome evolution process. However, experimental identification of recombination spots is both time-consuming and costly. Developing an accurate and automated method for reliably and ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-15-340

    authors: Li L,Yu S,Xiao W,Li Y,Huang L,Zheng X,Zhou S,Yang H

    更新日期:2014-11-20 00:00:00

  • An evidence-based approach to identify aging-related genes in Caenorhabditis elegans.

    abstract:BACKGROUND:Extensive studies have been carried out on Caenorhabditis elegans as a model organism to elucidate mechanisms of aging and the effects of perturbing known aging-related genes on lifespan and behavior. This research has generated large amounts of experimental data that is increasingly difficult to integrate a...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-015-0469-4

    authors: Callahan A,Cifuentes JJ,Dumontier M

    更新日期:2015-02-07 00:00:00

  • Homology modeling, molecular docking, and molecular dynamics simulations elucidated α-fetoprotein binding modes.

    abstract:BACKGROUND:An important mechanism of endocrine activity is chemicals entering target cells via transport proteins and then interacting with hormone receptors such as the estrogen receptor (ER). α-Fetoprotein (AFP) is a major transport protein in rodent serum that can bind and sequester estrogens, thus preventing entry ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-14-S14-S6

    authors: Shen J,Zhang W,Fang H,Perkins R,Tong W,Hong H

    更新日期:2013-01-01 00:00:00