Abstract:
BACKGROUND:We study the statistical properties of fragment coverage in genome sequencing experiments. In an extension of the classic Lander-Waterman model, we consider the effect of the length distribution of fragments. We also introduce a coding of the shape of the coverage depth function as a tree and explain how this can be used to detect regions with anomalous coverage. This modeling perspective is especially germane to current high-throughput sequencing experiments, where both sample preparation protocols and sequencing technology particulars can affect fragment length distributions. RESULTS:Under the mild assumptions that fragment start sites are Poisson distributed and successive fragment lengths are independent and identically distributed, we observe that, regardless of fragment length distribution, the fragments produced in a sequencing experiment can be viewed as resulting from a two-dimensional spatial Poisson process. We then study the successive jumps of the coverage function, and show that they can be encoded as a random tree that is approximately a Galton-Watson tree with generation-dependent geometric offspring distributions whose parameters can be computed. CONCLUSIONS:We extend standard analyses of shotgun sequencing that focus on coverage statistics at individual sites, and provide a null model for detecting deviations from random coverage in high-throughput sequence census based experiments. Our approach leads to explicit determinations of the null distributions of certain test statistics, while for others it greatly simplifies the approximation of their null distributions by simulation. Our focus on fragments also leads to a new approach to visualizing sequencing data that is of independent interest.
journal_name
BMC Bioinformaticsjournal_title
BMC bioinformaticsauthors
Evans SN,Hower V,Pachter Ldoi
10.1186/1471-2105-11-430subject
Has Abstractpub_date
2010-08-18 00:00:00pages
430issn
1471-2105pii
1471-2105-11-430journal_volume
11pub_type
杂志文章abstract:BACKGROUND:Pseudouridylation is the most prevalent type of posttranscriptional modification in various stable RNAs of all organisms, which significantly affects many cellular processes that are regulated by RNA. Thus, accurate identification of pseudouridine (Ψ) sites in RNA will be of great benefit for understanding t...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-018-2321-0
更新日期:2018-08-29 00:00:00
abstract:BACKGROUND:Schizophrenia, bipolar disorder, and major depression are devastating mental diseases, each with distinctive yet overlapping epidemiologic characteristics. Microarray and proteomics data have revealed genes which expressed abnormally in patients. Several single nucleotide polymorphisms (SNPs) and mutations a...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-12-S13-S20
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:In population genetics, simulation is a fundamental tool for analyzing how basic evolutionary forces such as natural selection, recombination, and mutation shape the genetic landscape of a population. Forward simulation represents the most powerful, but, at the same time, most compute-intensive approach for ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-14-216
更新日期:2013-07-09 00:00:00
abstract:BACKGROUND:Quadruplexes are specific structure motifs occurring, e.g., in telomeres and transcriptional regulatory regions. Recent discoveries confirmed their importance in biomedicine and led to an intensified examination of their properties. So far, the study of these motifs has focused mainly on the sequence and the...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-020-3385-1
更新日期:2020-01-31 00:00:00
abstract:BACKGROUND:Improvements in technology have been accompanied by the generation of large amounts of complex data. This same technology must be harnessed effectively if the knowledge stored within the data is to be retrieved. Storing data in ontologies aids its management; ontologies serve as controlled vocabularies that ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-6-74
更新日期:2005-03-24 00:00:00
abstract:BACKGROUND:A fundamental fact in biology states that genes do not operate in isolation, and yet, methods that infer regulatory networks for single cell gene expression data have been slow to emerge. With single cell sequencing methods now becoming accessible, general network inference algorithms that were initially dev...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-018-2217-z
更新日期:2018-06-19 00:00:00
abstract:BACKGROUND:The biological network is highly dynamic. Functional relations between genes can be activated or deactivated depending on the biological conditions. On the genome-scale network, subnetworks that gain or lose local expression consistency may shed light on the regulatory mechanisms related to the changing biol...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-019-3046-4
更新日期:2019-12-24 00:00:00
abstract:BACKGROUND:A common method for presenting and studying biological interaction networks is visualization. Software tools can enhance our ability to explore network visualizations and improve our understanding of biological systems, particularly when these tools offer analysis capabilities. However, most published networ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-10-95
更新日期:2009-03-26 00:00:00
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
更新日期:2006-08-18 00:00:00
abstract:BACKGROUND:High throughput DNA/RNA sequencing has revolutionized biological and clinical research. Sequencing is widely used, and generates very large amounts of data, mainly due to reduced cost and advanced technologies. Quickly assessing the quality of giga-to-tera base levels of sequencing data has become a routine ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-019-3015-y
更新日期:2019-08-15 00:00:00
abstract:BACKGROUND:A number of tools for the examination of linkage disequilibrium (LD) patterns between nearby alleles exist, but none are available for quickly and easily investigating LD at longer ranges (>500 kb). We have developed a web-based query tool (GLIDERS: Genome-wide LInkage DisEquilibrium Repository and Search en...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-10-367
更新日期:2009-10-31 00:00:00
abstract:BACKGROUND:RNA sequencing (RNA-seq) has become the standard means of analyzing gene and transcript expression in high-throughput. While previously sequence alignment was a time demanding step, fast alignment methods and even more so transcript counting methods which avoid mapping and quantify gene and transcript expres...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-019-2799-0
更新日期:2019-05-03 00:00:00
abstract:BACKGROUND:Microarray experiments enable simultaneous measurement of the expression levels of virtually all transcripts present in cells, thereby providing a 'molecular picture' of the cell state. On the other hand, the genomic responses to a pharmacological or hormonal stimulus are dynamic molecular processes, where t...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-9-S2-S12
更新日期:2008-03-26 00:00:00
abstract:BACKGROUND:Biclustering has been largely applied for the unsupervised analysis of biological data, being recognised today as a key technique to discover putative modules in both expression data (subsets of genes correlated in subsets of conditions) and network data (groups of coherently interconnected biological entiti...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-017-1493-3
更新日期:2017-02-02 00:00:00
abstract:BACKGROUND:Historically, two categories of computational algorithms (alignment-based and alignment-free) have been applied to sequence comparison-one of the most fundamental issues in bioinformatics. Multiple sequence alignment, although dominantly used by biologists, possesses both fundamental as well as computational...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-9-S6-S15
更新日期:2008-05-28 00:00:00
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
更新日期:2018-12-31 00:00:00
abstract:BACKGROUND:The imputation of missing values is necessary for the efficient use of DNA microarray data, because many clustering algorithms and some statistical analysis require a complete data set. A few imputation methods for DNA microarray data have been introduced, but the efficiency of the methods was low and the va...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-5-160
更新日期:2004-10-26 00:00:00
abstract:BACKGROUND:Accurate somatic mutation-calling is essential for insightful mutation analyses in cancer studies. Several mutation-callers are publicly available and more are likely to appear. Nonetheless, mutation-calling is still challenging and there is unlikely to be one established caller that systematically outperfor...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-15-154
更新日期:2014-05-21 00:00:00
abstract:BACKGROUND:One of key issues in the post-genomic era is to assign functions to uncharacterized proteins. Since proteins seldom act alone; rather, they must interact with other biomolecular units to execute their functions. Thus, the functions of unknown proteins may be discovered through studying their interactions wit...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-11-S1-S64
更新日期:2010-01-18 00:00:00
abstract:BACKGROUND:Microarray experiments, as well as other genomic analyses, often result in large gene sets containing up to several hundred genes. The biological significance of such sets of genes is, usually, not readily apparent. Identification of the functions of the genes in the set can help highlight features of intere...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-6-189
更新日期:2005-07-25 00:00:00
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
更新日期:2017-05-31 00:00:00
abstract:BACKGROUND:Although both conservation and correlated mutation (CM) are important information reflecting the different sorts of context in multiple sequence alignment, most of alignment methods use sequence profiles that only represent conservation. There is no general way to represent correlated mutation and incorporat...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-11-S2-S2
更新日期:2010-04-16 00:00:00
abstract:BACKGROUND:Machine learning has been utilized to predict cancer drug response from multi-omics data generated from sensitivities of cancer cell lines to different therapeutic compounds. Here, we build machine learning models using gene expression data from patients' primary tumor tissues to predict whether a patient wi...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-020-03690-4
更新日期:2020-09-30 00:00:00
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
更新日期:2020-09-16 00:00:00
abstract:BACKGROUNDS:Next-Generation Sequencing (NGS) is now widely used in biomedical research for various applications. Processing of NGS data requires multiple programs and customization of the processing pipelines according to the data platforms. However, rapid progress of the NGS applications and processing methods urgentl...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-019-2676-x
更新日期:2019-02-20 00:00:00
abstract:BACKGROUND:The Acel_2062 protein from Acidothermus cellulolyticus is a protein of unknown function. Initial sequence analysis predicted that it was a metallopeptidase from the presence of a motif conserved amongst the Asp-zincins, which are peptidases that contain a single, catalytic zinc ion ligated by the histidines ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-15-1
更新日期:2014-01-03 00:00:00
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
更新日期:2014-11-28 00:00:00
abstract:BACKGROUND:In omics data integration studies, it is common, for a variety of reasons, for some individuals to not be present in all data tables. Missing row values are challenging to deal with because most statistical methods cannot be directly applied to incomplete datasets. To overcome this issue, we propose a multip...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-016-1273-5
更新日期:2016-10-03 00:00:00
abstract:BACKGROUND:Great strides have been made in the effective treatment of HIV-1 with the development of second-generation protease inhibitors (PIs) that are effective against historically multi-PI-resistant HIV-1 variants. Nevertheless, mutation patterns that confer decreasing susceptibility to available PIs continue to ar...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-12-477
更新日期:2011-12-15 00:00:00
abstract:BACKGROUND:Targeted resequencing offers a cost-effective alternative to whole-genome and whole-exome sequencing when investigating regions known to be associated with a trait or disease. There are a number of approaches to targeted resequencing, including microfluidic PCR amplification, which may be enhanced by multipl...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-016-1453-3
更新日期:2017-01-05 00:00:00