Accuracy of RNA-Seq and its dependence on sequencing depth.

Abstract:

BACKGROUND:The cost of DNA sequencing has undergone a dramatical reduction in the past decade. As a result, sequencing technologies have been increasingly applied to genomic research. RNA-Seq is becoming a common technique for surveying gene expression based on DNA sequencing. As it is not clear how increased sequencing capacity has affected measurement accuracy of mRNA, we sought to investigate that relationship. RESULT:We empirically evaluate the accuracy of repeated gene expression measurements using RNA-Seq. We identify library preparation steps prior to DNA sequencing as the main source of error in this process. Studying three datasets, we show that the accuracy indeed improves with the sequencing depth. However, the rate of improvement as a function of sequence reads is generally slower than predicted by the binomial distribution. We therefore used the beta-binomial distribution to model the overdispersion. The overdispersion parameters we introduced depend explicitly on the number of reads so that the resulting statistical uncertainty is consistent with the empirical data that measurement accuracy increases with the sequencing depth. The overdispersion parameters were determined by maximizing the likelihood. We shown that our modified beta-binomial model had lower false discovery rate than the binomial or the pure beta-binomial models. CONCLUSION:We proposed a novel form of overdispersion guaranteeing that the accuracy improves with sequencing depth. We demonstrated that the new form provides a better fit to the data.

journal_name

BMC Bioinformatics

journal_title

BMC bioinformatics

authors

Cai G,Li H,Lu Y,Huang X,Lee J,Müller P,Ji Y,Liang S

doi

10.1186/1471-2105-13-S13-S5

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

S5

issn

1471-2105

pii

1471-2105-13-S13-S5

journal_volume

13 Suppl 13

pub_type

杂志文章
  • Correlation analysis reveals the emergence of coherence in the gene expression dynamics following system perturbation.

    abstract::Time course gene expression experiments are a popular means to infer co-expression. Many methods have been proposed to cluster genes or to build networks based on similarity measures of their expression dynamics. In this paper we apply a correlation based approach to network reconstruction to three datasets of time se...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-8-S1-S16

    authors: Neretti N,Remondini D,Tatar M,Sedivy JM,Pierini M,Mazzatti D,Powell J,Franceschi C,Castellani GC

    更新日期:2007-03-08 00:00:00

  • GeneLibrarian: an effective gene-information summarization and visualization system.

    abstract:BACKGROUND:Abundant information about gene products is stored in online searchable databases such as annotation or literature. To efficiently obtain and digest such information, there is a pressing need for automated information-summarization and functional-similarity clustering of genes. RESULTS:We have developed a n...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-7-392

    authors: Chiang JH,Shin JW,Liu HH,Chin CL

    更新日期:2006-08-29 00:00:00

  • A Web-based and Grid-enabled dChip version for the analysis of large sets of gene expression data.

    abstract:BACKGROUND:Microarray techniques are one of the main methods used to investigate thousands of gene expression profiles for enlightening complex biological processes responsible for serious diseases, with a great scientific impact and a wide application area. Several standalone applications had been developed in order t...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-9-480

    authors: Corradi L,Fato M,Porro I,Scaglione S,Torterolo L

    更新日期:2008-11-13 00:00:00

  • Hotspot Hunter: a computational system for large-scale screening and selection of candidate immunological hotspots in pathogen proteomes.

    abstract:BACKGROUND:T-cell epitopes that promiscuously bind to multiple alleles of a human leukocyte antigen (HLA) supertype are prime targets for development of vaccines and immunotherapies because they are relevant to a large proportion of the human population. The presence of clusters of promiscuous T-cell epitopes, immunolo...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-9-S1-S19

    authors: Zhang GL,Khan AM,Srinivasan KN,Heiny A,Lee K,Kwoh CK,August JT,Brusic V

    更新日期:2008-01-01 00:00:00

  • Ontology driven integration platform for clinical and translational research.

    abstract::Semantic Web technologies offer a promising framework for integration of disparate biomedical data. In this paper we present the semantic information integration platform under development at the Center for Clinical and Translational Sciences (CCTS) at the University of Texas Health Science Center at Houston (UTHSC-H)...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-10-S2-S2

    authors: Mirhaji P,Zhu M,Vagnoni M,Bernstam EV,Zhang J,Smith JW

    更新日期:2009-02-05 00:00:00

  • Linear space string correction algorithm using the Damerau-Levenshtein distance.

    abstract:BACKGROUND:The Damerau-Levenshtein (DL) distance metric has been widely used in the biological science. It tries to identify the similar region of DNA,RNA and protein sequences by transforming one sequence to the another using the substitution, insertion, deletion and transposition operations. Lowrance and Wagner have ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-019-3184-8

    authors: Zhao C,Sahni S

    更新日期:2020-12-09 00:00:00

  • HMM Logos for visualization of protein families.

    abstract:BACKGROUND:Profile Hidden Markov Models (pHMMs) are a widely used tool for protein family research. Up to now, however, there exists no method to visualize all of their central aspects graphically in an intuitively understandable way. RESULTS:We present a visualization method that incorporates both emission and transi...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-5-7

    authors: Schuster-Böckler B,Schultz J,Rahmann S

    更新日期:2004-01-21 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

  • Meta-aligner: long-read alignment based on genome statistics.

    abstract:BACKGROUND:Current development of sequencing technologies is towards generating longer and noisier reads. Evidently, accurate alignment of these reads play an important role in any downstream analysis. Similarly, reducing the overall cost of sequencing is related to the time consumption of the aligner. The tradeoff bet...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-017-1518-y

    authors: Nashta-Ali D,Aliyari A,Ahmadian Moghadam A,Edrisi MA,Motahari SA,Hossein Khalaj B

    更新日期:2017-02-23 00:00:00

  • Identifying target processes for microbial electrosynthesis by elementary mode analysis.

    abstract:BACKGROUND:Microbial electrosynthesis and electro fermentation are techniques that aim to optimize microbial production of chemicals and fuels by regulating the cellular redox balance via interaction with electrodes. While the concept is known for decades major knowledge gaps remain, which make it hard to evaluate its ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-014-0410-2

    authors: Kracke F,Krömer JO

    更新日期:2014-12-30 00:00:00

  • Constructing a meaningful evolutionary average at the phylogenetic center of mass.

    abstract:BACKGROUND:As a consequence of the evolutionary process, data collected from related species tend to be similar. This similarity by descent can obscure subtler signals in the data such as the evidence of constraint on variation due to shared selective pressures. In comparative sequence analysis, for example, sequence s...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-8-222

    authors: Stone EA,Sidow A

    更新日期:2007-06-26 00:00:00

  • Identification of conserved gene clusters in multiple genomes based on synteny and homology.

    abstract:BACKGROUND:Uncovering the relationship between the conserved chromosomal segments and the functional relatedness of elements within these segments is an important question in computational genomics. We build upon the series of works on gene teams and homology teams. RESULTS:Our primary contribution is a local sliding-...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-12-S9-S18

    authors: Sarkar A,Soueidan H,Nikolski M

    更新日期:2011-10-05 00:00:00

  • TooT-T: discrimination of transport proteins from non-transport proteins.

    abstract:BACKGROUND:Membrane transport proteins (transporters) play an essential role in every living cell by transporting hydrophilic molecules across the hydrophobic membranes. While the sequences of many membrane proteins are known, their structure and function is still not well characterized and understood, owing to the imm...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-019-3311-6

    authors: Alballa M,Butler G

    更新日期:2020-04-23 00:00:00

  • Cell subset prediction for blood genomic studies.

    abstract:BACKGROUND:Genome-wide transcriptional profiling of patient blood samples offers a powerful tool to investigate underlying disease mechanisms and personalized treatment decisions. Most studies are based on analysis of total peripheral blood mononuclear cells (PBMCs), a mixed population. In this case, accuracy is inhere...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-12-258

    authors: Bolen CR,Uduman M,Kleinstein SH

    更新日期:2011-06-24 00:00:00

  • SitesIdentify: a protein functional site prediction tool.

    abstract:BACKGROUND:The rate of protein structures being deposited in the Protein Data Bank surpasses the capacity to experimentally characterise them and therefore computational methods to analyse these structures have become increasingly important. Identifying the region of the protein most likely to be involved in function i...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-10-379

    authors: Bray T,Chan P,Bougouffa S,Greaves R,Doig AJ,Warwicker J

    更新日期:2009-11-18 00:00:00

  • Proceedings of the 2018 MidSouth Computational Biology and Bioinformatics Society (MCBIOS) conference.

    abstract:: ...

    journal_title:BMC bioinformatics

    pub_type: 历史文章,杂志文章

    doi:10.1186/s12859-019-2618-7

    authors: Wren JD,Doerkson RJ,Toby IT,Nanduri B,Homayouni R,Manda P,Thakkar S

    更新日期:2019-03-14 00:00:00

  • metaBEETL: high-throughput analysis of heterogeneous microbial populations from shotgun DNA sequences.

    abstract::Environmental shotgun sequencing (ESS) has potential to give greater insight into microbial communities than targeted sequencing of 16S regions, but requires much higher sequence coverage. The advent of next-generation sequencing has made it feasible for the Human Microbiome Project and other initiatives to generate E...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-14-S5-S2

    authors: Ander C,Schulz-Trieglaff OB,Stoye J,Cox AJ

    更新日期:2013-01-01 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

  • Identifying cancer mutation targets across thousands of samples: MuteProc, a high throughput mutation analysis pipeline.

    abstract:BACKGROUND:In the past decade, bioinformatics tools have matured enough to reliably perform sophisticated primary data analysis on Next Generation Sequencing (NGS) data, such as mapping, assemblies and variant calling, however, there is still a dire need for improvements in the higher level analysis such as NGS data or...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-14-167

    authors: Hadj Khodabakhshi A,Fejes AP,Birol I,Jones SJ

    更新日期:2013-05-28 00:00:00

  • Meta-eQTL: a tool set for flexible eQTL meta-analysis.

    abstract:BACKGROUND:Increasing number of eQTL (Expression Quantitative Trait Loci) datasets facilitate genetics and systems biology research. Meta-analysis tools are in need to jointly analyze datasets of same or similar issue types to improve statistical power especially in trans-eQTL mapping. Meta-analysis framework is also n...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-014-0392-0

    authors: Di Narzo AF,Cheng H,Lu J,Hao K

    更新日期:2014-11-28 00:00:00

  • An optimized TOPS+ comparison method for enhanced TOPS models.

    abstract:BACKGROUND:Although methods based on highly abstract descriptions of protein structures, such as VAST and TOPS, can perform very fast protein structure comparison, the results can lack a high degree of biological significance. Previously we have discussed the basic mechanisms of our novel method for structure compariso...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-11-138

    authors: Veeramalai M,Gilbert D,Valiente G

    更新日期:2010-03-17 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

  • 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

  • Modeling genomic data with type attributes, balancing stability and maintainability.

    abstract:BACKGROUND:Molecular biology (MB) is a dynamic research domain that benefits greatly from the use of modern software technology in preparing experiments, analyzing acquired data, and even performing "in-silico" analyses. As ever new findings change the face of this domain, software for MB has to be sufficiently flexibl...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-10-97

    authors: Busch N,Wedemann G

    更新日期:2009-03-27 00:00:00

  • Texture based skin lesion abruptness quantification to detect malignancy.

    abstract:BACKGROUND:Abruptness of pigment patterns at the periphery of a skin lesion is one of the most important dermoscopic features for detection of malignancy. In current clinical setting, abrupt cutoff of a skin lesion determined by an examination of a dermatologist. This process is subjective, nonquantitative, and error-p...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-017-1892-5

    authors: Erol R,Bayraktar M,Kockara S,Kaya S,Halic T

    更新日期:2017-12-28 00:00:00

  • Comparative evaluation of gene set analysis approaches for RNA-Seq data.

    abstract:BACKGROUND:Over the last few years transcriptome sequencing (RNA-Seq) has almost completely taken over microarrays for high-throughput studies of gene expression. Currently, the most popular use of RNA-Seq is to identify genes which are differentially expressed between two or more conditions. Despite the importance of ...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/s12859-014-0397-8

    authors: Rahmatallah Y,Emmert-Streib F,Glazko G

    更新日期:2014-12-05 00:00:00

  • Knowledge-guided multi-scale independent component analysis for biomarker identification.

    abstract:BACKGROUND:Many statistical methods have been proposed to identify disease biomarkers from gene expression profiles. However, from gene expression profile data alone, statistical methods often fail to identify biologically meaningful biomarkers related to a specific disease under study. In this paper, we develop a nove...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-9-416

    authors: Chen L,Xuan J,Wang C,Shih IeM,Wang Y,Zhang Z,Hoffman E,Clarke R

    更新日期:2008-10-06 00:00:00

  • A comparative study of conservation and variation scores.

    abstract:BACKGROUND:Conservation and variation scores are used when evaluating sites in a multiple sequence alignment, in order to identify residues critical for structure or function. A variety of scores are available today but it is not clear how different scores relate to each other. RESULTS:We applied 25 conservation and v...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-11-388

    authors: Johansson F,Toh H

    更新日期:2010-07-21 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

  • Learning smoothing models of copy number profiles using breakpoint annotations.

    abstract:BACKGROUND:Many models have been proposed to detect copy number alterations in chromosomal copy number profiles, but it is usually not obvious to decide which is most effective for a given data set. Furthermore, most methods have a smoothing parameter that determines the number of breakpoints and must be chosen using v...

    journal_title:BMC bioinformatics

    pub_type: 杂志文章

    doi:10.1186/1471-2105-14-164

    authors: Hocking TD,Schleiermacher G,Janoueix-Lerosey I,Boeva V,Cappo J,Delattre O,Bach F,Vert JP

    更新日期:2013-05-22 00:00:00