Comparison of haplotype-based tests for detecting gene-environment interactions with rare variants.

Abstract:

:Dissecting the genetic mechanism underlying a complex disease hinges on discovering gene-environment interactions (GXE). However, detecting GXE is a challenging problem especially when the genetic variants under study are rare. Haplotype-based tests have several advantages over the so-called collapsing tests for detecting rare variants as highlighted in recent literature. Thus, it is of practical interest to compare haplotype-based tests for detecting GXE including the recent ones developed specifically for rare haplotypes. We compare the following methods: haplo.glm, hapassoc, HapReg, Bayesian hierarchical generalized linear model (BhGLM) and logistic Bayesian LASSO (LBL). We simulate data under different types of association scenarios and levels of gene-environment dependence. We find that when the type I error rates are controlled to be the same for all methods, LBL is the most powerful method for detecting GXE. We applied the methods to a lung cancer data set, in particular, in region 15q25.1 as it has been suggested in the literature that it interacts with smoking to affect the lung cancer susceptibility and that it is associated with smoking behavior. LBL and BhGLM were able to detect a rare haplotype-smoking interaction in this region. We also analyzed the sequence data from the Dallas Heart Study, a population-based multi-ethnic study. Specifically, we considered haplotype blocks in the gene ANGPTL4 for association with trait serum triglyceride and used ethnicity as a covariate. Only LBL found interactions of haplotypes with race (Hispanic). Thus, in general, LBL seems to be the best method for detecting GXE among the ones we studied here. Nonetheless, it requires the most computation time.

journal_name

Brief Bioinform

authors

Papachristou C,Biswas S

doi

10.1093/bib/bbz031

subject

Has Abstract

pub_date

2020-05-21 00:00:00

pages

851-862

issue

3

eissn

1467-5463

issn

1477-4054

pii

5475052

journal_volume

21

pub_type

杂志文章
  • Bioinformatics resources for SARS-CoV-2 discovery and surveillance.

    abstract::In early January 2020, the novel coronavirus (SARS-CoV-2) responsible for a pneumonia outbreak in Wuhan, China, was identified using next-generation sequencing (NGS) and readily available bioinformatics pipelines. In addition to virus discovery, these NGS technologies and bioinformatics resources are currently being e...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbaa386

    authors: Hu T,Li J,Zhou H,Li C,Holmes EC,Shi W

    更新日期:2021-01-08 00:00:00

  • Toward more realistic drug-target interaction predictions.

    abstract::A number of supervised machine learning models have recently been introduced for the prediction of drug-target interactions based on chemical structure and genomic sequence information. Although these models could offer improved means for many network pharmacology applications, such as repositioning of drugs for new t...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbu010

    authors: Pahikkala T,Airola A,Pietilä S,Shakyawar S,Szwajda A,Tang J,Aittokallio T

    更新日期:2015-03-01 00:00:00

  • Systems pharmacology in drug discovery and therapeutic insight for herbal medicines.

    abstract::Systems pharmacology is an emerging field that integrates systems biology and pharmacology to advance the process of drug discovery, development and the understanding of therapeutic mechanisms. The aim of the present work is to highlight the role that the systems pharmacology plays across the traditional herbal medici...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbt035

    authors: Huang C,Zheng C,Li Y,Wang Y,Lu A,Yang L

    更新日期:2014-09-01 00:00:00

  • Visualising gene expression in its metabolic context.

    abstract::Relative changes in mRNA as well as protein levels induced by sublethal doses of antibiotics on bacteria are measured and results visualised in the context of metabolic pathway diagrams. The mRNA levels present at a given time point after the addition of the antibiotic are measured using microarrays from Affymetrix. A...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/1.3.297

    authors: Wolf D,Gray CP,de Saizieu A

    更新日期:2000-09-01 00:00:00

  • Computational knowledge integration in biopharmaceutical research.

    abstract::An initiative to increase biopharmaceutical research productivity by capturing, sharing and computationally integrating proprietary scientific discoveries with public knowledge is described. This initiative involves both organisational process change and multiple interoperating software systems. The software component...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/4.3.260

    authors: Ficenec D,Osborne M,Pradines J,Richards D,Felciano R,Cho RJ,Chen RO,Liefeld T,Owen J,Ruttenberg A,Reich C,Horvath J,Clark T

    更新日期:2003-09-01 00:00:00

  • A proteogenomic approach to understand splice isoform functions through sequence and expression-based computational modeling.

    abstract::The products of multi-exon genes are a mixture of alternatively spliced isoforms, from which the translated proteins can have similar, different or even opposing functions. It is therefore essential to differentiate and annotate functions for individual isoforms. Computational approaches provide an efficient complemen...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbv109

    authors: Li HD,Omenn GS,Guan Y

    更新日期:2016-11-01 00:00:00

  • MeSHHeading2vec: a new method for representing MeSH headings as vectors based on graph embedding algorithm.

    abstract::Effectively representing Medical Subject Headings (MeSH) headings (terms) such as disease and drug as discriminative vectors could greatly improve the performance of downstream computational prediction models. However, these terms are often abstract and difficult to quantify. In this paper, we converted the MeSH tree ...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbaa037

    authors: Guo ZH,You ZH,Huang DS,Yi HC,Zheng K,Chen ZH,Wang YB

    更新日期:2020-03-31 00:00:00

  • Characteristics and evolution of the ecosystem of software tools supporting research in molecular biology.

    abstract::Daily work in molecular biology presently depends on a large number of computational tools. An in-depth, large-scale study of that 'ecosystem' of Web tools, its characteristics, interconnectivity, patterns of usage/citation, temporal evolution and rate of decay is crucial for understanding the forces that shape it and...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bby001

    authors: Pazos F,Chagoyen M

    更新日期:2019-07-19 00:00:00

  • SARS-CoV-2 hot-spot mutations are significantly enriched within inverted repeats and CpG island loci.

    abstract::SARS-CoV-2 is an intensively investigated virus from the order Nidovirales (Coronaviridae family) that causes COVID-19 disease in humans. Through enormous scientific effort, thousands of viral strains have been sequenced to date, thereby creating a strong background for deep bioinformatics studies of the SARS-CoV-2 ge...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbaa385

    authors: Goswami P,Bartas M,Lexa M,Bohálová N,Volná A,Červeň J,Červeňová V,Pečinka P,Špunda V,Fojta M,Brázda V

    更新日期:2020-12-21 00:00:00

  • Sequencing technologies and tools for short tandem repeat variation detection.

    abstract::Short tandem repeats are highly polymorphic and associated with a wide range of phenotypic variation, some of which cause neurodegenerative disease in humans. With advances in high-throughput sequencing technologies, there are novel opportunities to study genetic variation. While available sequencing technologies and ...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章,评审

    doi:10.1093/bib/bbu001

    authors: Cao MD,Balasubramanian S,Bodén M

    更新日期:2015-03-01 00:00:00

  • Comparative analysis of methods for genome-wide nucleosome cartography.

    abstract::Nucleosomes contribute to compacting the genome into the nucleus and regulate the physical access of regulatory proteins to DNA either directly or through the epigenetic modifications of the histone tails. Precise mapping of nucleosome positioning across the genome is, therefore, essential to understanding the genome ...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbu037

    authors: Quintales L,Vázquez E,Antequera F

    更新日期:2015-07-01 00:00:00

  • An open-pollinated design for mapping imprinting genes in natural populations.

    abstract::With the increasing recognition of its role in trait and disease development, it is crucial to account for genetic imprinting to illustrate the genetic architecture of complex traits. Genetic mapping can be innovated to test and estimate effects of genetic imprinting in a segregating population derived from experiment...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbu019

    authors: Sun L,Zhu X,Bo W,Xu F,Cheng T,Zhang Q,Wu R

    更新日期:2015-05-01 00:00:00

  • Comparison of software packages for detecting differential expression in RNA-seq studies.

    abstract::RNA-sequencing (RNA-seq) has rapidly become a popular tool to characterize transcriptomes. A fundamental research problem in many RNA-seq studies is the identification of reliable molecular markers that show differential expression between distinct sample groups. Together with the growing popularity of RNA-seq, a numb...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbt086

    authors: Seyednasrollah F,Laiho A,Elo LL

    更新日期:2015-01-01 00:00:00

  • Unraveling chloroplast transcriptomes with ChloroSeq, an organelle RNA-Seq bioinformatics pipeline.

    abstract::Online sequence repositories are teeming with RNA sequencing (RNA-Seq) data from a wide range of eukaryotes. Although most of these data sets contain large numbers of organelle-derived reads, researchers tend to ignore these data, focusing instead on the nuclear-derived transcripts. Consequently, GenBank contains mass...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbw088

    authors: Smith DR,Sanitá Lima M

    更新日期:2017-11-01 00:00:00

  • New developments of alignment-free sequence comparison: measures, statistics and next-generation sequencing.

    abstract::With the development of next-generation sequencing (NGS) technologies, a large amount of short read data has been generated. Assembly of these short reads can be challenging for genomes and metagenomes without template sequences, making alignment-based genome sequence comparison difficult. In addition, sequence reads ...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章,评审

    doi:10.1093/bib/bbt067

    authors: Song K,Ren J,Reinert G,Deng M,Waterman MS,Sun F

    更新日期:2014-05-01 00:00:00

  • Comprehensive characterization of tissue-specific circular RNAs in the human and mouse genomes.

    abstract::Circular RNA (circRNA) is a group of RNA family generated by RNA circularization, which was discovered ubiquitously across different species and tissues. However, there is no global view of tissue specificity for circRNAs to date. Here we performed the comprehensive analysis to characterize the features of human and m...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbw081

    authors: Xia S,Feng J,Lei L,Hu J,Xia L,Wang J,Xiang Y,Liu L,Zhong S,Han L,He C

    更新日期:2017-11-01 00:00:00

  • Class-imbalanced classifiers for high-dimensional data.

    abstract::A class-imbalanced classifier is a decision rule to predict the class membership of new samples from an available data set where the class sizes differ considerably. When the class sizes are very different, most standard classification algorithms may favor the larger (majority) class resulting in poor accuracy in the ...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章,评审

    doi:10.1093/bib/bbs006

    authors: Lin WJ,Chen JJ

    更新日期:2013-01-01 00:00:00

  • Machine learning meets genome assembly.

    abstract:MOTIVATION:With the recent advances in DNA sequencing technologies, the study of the genetic composition of living organisms has become more accessible for researchers. Several advances have been achieved because of it, especially in the health sciences. However, many challenges which emerge from the complexity of sequ...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章,评审

    doi:10.1093/bib/bby072

    authors: Padovani de Souza K,Setubal JC,Ponce de Leon F de Carvalho AC,Oliveira G,Chateau A,Alves R

    更新日期:2019-11-27 00:00:00

  • TRCirc: a resource for transcriptional regulation information of circRNAs.

    abstract::In recent years, high-throughput genomic technologies like chromatin immunoprecipitation sequencing (ChIp-seq) and transcriptome sequencing (RNA-seq) have been becoming both more refined and less expensive, making them more accessible. Many circular RNAs (circRNAs) that originate from back-spliced exons have been iden...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bby083

    authors: Tang Z,Li X,Zhao J,Qian F,Feng C,Li Y,Zhang J,Jiang Y,Yang Y,Wang Q,Li C

    更新日期:2019-11-27 00:00:00

  • A survey of software tools for microRNA discovery and characterization using RNA-seq.

    abstract::Since the small RNA-sequencing (sRNA-seq) technology became available, it allowed the discovery of thousands new microRNAs (miRNAs) in humans and many other species, providing new data on these small RNAs (sRNAs) of high biological and translational relevance. MiRNA discovery has not yet reached saturation, even in th...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbx148

    authors: Bortolomeazzi M,Gaffo E,Bortoluzzi S

    更新日期:2019-05-21 00:00:00

  • Circular RNA identification based on multiple seed matching.

    abstract::Computational detection methods have been widely used in studies on the biogenesis and the function of circular RNAs (circRNAs). However, all of the existing tools showed disadvantages on certain aspects of circRNA detection. Here, we propose an improved multithreading detection tool, CIRI2, which used an adapted maxi...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbx014

    authors: Gao Y,Zhang J,Zhao F

    更新日期:2018-09-28 00:00:00

  • Computational prediction and analysis of species-specific fungi phosphorylation via feature optimization strategy.

    abstract::Protein phosphorylation is a reversible and ubiquitous post-translational modification that primarily occurs at serine, threonine and tyrosine residues and regulates a variety of biological processes. In this paper, we first briefly summarized the current progresses in computational prediction of eukaryotic protein ph...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bby122

    authors: Cao M,Chen G,Yu J,Shi S

    更新日期:2020-03-23 00:00:00

  • TOD-CUP: a gene expression rank-based majority vote algorithm for tissue origin diagnosis of cancers of unknown primary.

    abstract::Gene expression profiling holds great potential as a new approach to histological diagnosis and precision medicine of cancers of unknown primary (CUP). Batch effects and different data types greatly decrease the predictive performance of biomarker-based algorithms, and few methods have been widely applied to identify ...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbaa031

    authors: Shen Y,Chu Q,Yin X,He Y,Bai P,Wang Y,Fang W,Timko MP,Fan L,Jiang W

    更新日期:2020-04-08 00:00:00

  • In silico signaling modeling to understand cancer pathways and treatment responses.

    abstract::Precision medicine has changed thinking in cancer therapy, highlighting a better understanding of the individual clinical interventions. But what role do the drivers and pathways identified from pan-cancer genome analysis play in the tumor? In this letter, we will highlight the importance of in silico modeling in prec...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbz033

    authors: Kunz M,Jeromin J,Fuchs M,Christoph J,Veronesi G,Flentje M,Nietzer S,Dandekar G,Dandekar T

    更新日期:2020-05-21 00:00:00

  • GenoPheno: cataloging large-scale phenotypic and next-generation sequencing data within human datasets.

    abstract::Precision medicine promises to revolutionize treatment, shifting therapeutic approaches from the classical one-size-fits-all to those more tailored to the patient's individual genomic profile, lifestyle and environmental exposures. Yet, to advance precision medicine's main objective-ensuring the optimum diagnosis, tre...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbaa033

    authors: Gutiérrez-Sacristán A,De Niz C,Kothari C,Kong SW,Mandl KD,Avillach P

    更新日期:2021-01-18 00:00:00

  • Agents in bioinformatics, computational and systems biology.

    abstract::The adoption of agent technologies and multi-agent systems constitutes an emerging area in bioinformatics. In this article, we report on the activity of the Working Group on Agents in Bioinformatics (BIOAGENTS) founded during the first AgentLink III Technical Forum meeting on the 2nd of July, 2004, in Rome. The meetin...

    journal_title:Briefings in bioinformatics

    pub_type:

    doi:10.1093/bib/bbl014

    authors: Merelli E,Armano G,Cannata N,Corradini F,d'Inverno M,Doms A,Lord P,Martin A,Milanesi L,Möller S,Schroeder M,Luck M

    更新日期:2007-01-01 00:00:00

  • Identifying miRNAs, targets and functions.

    abstract::microRNAs (miRNAs) are small endogenous non-coding RNAs that function as the universal specificity factors in post-transcriptional gene silencing. Discovering miRNAs, identifying their targets and further inferring miRNA functions have been a critical strategy for understanding normal biological processes of miRNAs an...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章,评审

    doi:10.1093/bib/bbs075

    authors: Liu B,Li J,Cairns MJ

    更新日期:2014-01-01 00:00:00

  • Computational biology for cardiovascular biomarker discovery.

    abstract::Computational biology is essential in the process of translating biological knowledge into clinical practice, as well as in the understanding of biological phenomena based on the resources and technologies originating from the clinical environment. One such key contribution of computational biology is the discovery of...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbp008

    authors: Azuaje F,Devaux Y,Wagner D

    更新日期:2009-07-01 00:00:00

  • Pattern recognition analysis on long noncoding RNAs: a tool for prediction in plants.

    abstract:MOTIVATION:Long noncoding RNAs (lncRNAs) correspond to a eukaryotic noncoding RNA class that gained great attention in the past years as a higher layer of regulation for gene expression in cells. There is, however, a lack of specific computational approaches to reliably predict lncRNA in plants, which contrast the vari...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章,评审

    doi:10.1093/bib/bby034

    authors: Negri TDC,Alves WAL,Bugatti PH,Saito PTM,Domingues DS,Paschoal AR

    更新日期:2019-03-25 00:00:00

  • MITGARD: an automated pipeline for mitochondrial genome assembly in eukaryotic species using RNA-seq data.

    abstract:MOTIVATION:Over the past decade, the field of next-generation sequencing (NGS) has seen dramatic advances in methods and a decrease in costs. Consequently, a large expansion of data has been generated by NGS, most of which have originated from RNA-sequencing (RNA-seq) experiments. Because mitochondrial genes are expres...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbaa429

    authors: Nachtigall PG,Grazziotin FG,Junqueira-de-Azevedo ILM

    更新日期:2021-01-30 00:00:00