Abstract:
BACKGROUND:An approach to molecular classification based on the comparative expression of protein pairs is presented. The method overcomes some of the present limitations in using peptide intensity data for class prediction for problems such as the detection of a disease, disease prognosis, or for predicting treatment response. Data analysis is particularly challenging in these situations due to sample size (typically tens) being much smaller than the large number of peptides (typically thousands). Methods based upon high dimensional statistical models, machine learning or other complex classifiers generate decisions which may be very accurate but can be complex and difficult to interpret in simple or biologically meaningful terms. A classification scheme, called ProtPair, is presented that generates simple decision rules leading to accurate classification which is based on measurement of very few proteins and requires only relative expression values, providing specific targeted hypotheses suitable for straightforward validation. RESULTS:ProtPair has been tested against clinical data from 21 patients following a bone marrow transplant, 13 of which progress to idiopathic pneumonia syndrome (IPS). The approach combines multiple peptide pairs originating from the same set of proteins, with each unique peptide pair providing an independent measure of discriminatory power. The prediction rate of the ProtPair for IPS study as measured by leave-one-out CV is 69.1%, which can be very beneficial for clinical diagnosis as it may flag patients in need of closer monitoring. The "top ranked" proteins provided by ProtPair are known to be associated with the biological processes and pathways intimately associated with known IPS biology based on mouse models. CONCLUSIONS:An approach to biomarker discovery, called ProtPair, is presented. ProtPair is based on the differential expression of pairs of peptides and the associated proteins. Using mass spectrometry data from "bottom up" proteomics methods, functionally related proteins/peptide pairs exhibiting co-ordinated changes expression profile are discovered, which represent a signature for patients progressing to various disease conditions. The method has been tested against clinical data from patients progressing to idiopthatic pneumonia syndrome (IPS) following a bone marrow transplant. The data indicates that patients with improper regulation in the concentration of specific acute phase response proteins at the time of bone marrow transplant are highly likely to develop IPS within few weeks. The results lead to a specific set of protein pairs that can be efficiently verified by investigating the pairwise abundance change in independent cohorts using ELISA or targeted mass spectrometry techniques. This generalized classifier can be extended to other clinical problems in a variety of contexts.
journal_name
BMC Bioinformaticsjournal_title
BMC bioinformaticsauthors
Kaur P,Schlatzer D,Cooke K,Chance MRdoi
10.1186/1471-2105-13-191subject
Has Abstractpub_date
2012-08-07 00:00:00pages
191issn
1471-2105pii
1471-2105-13-191journal_volume
13pub_type
杂志文章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
更新日期:2008-05-26 00:00:00
abstract:BACKGROUND:Ontology term labels can be ambiguous and have multiple senses. While this is no problem for human annotators, it is a challenge to automated methods, which identify ontology terms in text. Classical approaches to word sense disambiguation use co-occurring words or terms. However, most treat ontologies as si...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-10-28
更新日期:2009-01-21 00:00:00
abstract:BACKGROUND:A standardized and cost-effective molecular identification system is now an urgent need for Fungi owing to their wide involvement in human life quality. In particular the potential use of mitochondrial DNA species markers has been taken in account. Unfortunately, a serious difficulty in the PCR and bioinform...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-10-S6-S15
更新日期:2009-06-16 00:00:00
abstract:BACKGROUND:Peptidases are proteolytic enzymes responsible for fundamental cellular activities in all organisms. Apparently about 2-5% of the genes encode for peptidases, irrespectively of the organism source. The basic peptidase function is "protein digestion" and this can be potentially dangerous in living organisms w...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-8-S1-S3
更新日期:2007-03-08 00:00:00
abstract:BACKGROUND:Physical maps have been historically one of the cornerstones of genome sequencing and map-based cloning strategies. They also support marker assisted breeding and EST mapping. The problem of building a high quality physical map is computationally challenging due to unavoidable noise in the input fingerprint ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-10-217
更新日期:2009-07-15 00:00:00
abstract:BACKGROUND:This study addresses a recurrent biological problem, that is to define a formal clustering structure for a set of tissues on the basis of the relative abundance of multiple alternatively spliced isoforms mRNAs generated by the same gene. To this aim, we have used a model-based clustering approach, based on a...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-015-0689-7
更新日期:2015-09-15 00:00:00
abstract:BACKGROUND:Transcriptome sequencing is a powerful tool for measuring gene expression, but as well as some other technologies, various artifacts and biases affect the quantification. In order to correct some of them, several normalization approaches have emerged, differing both in the statistical strategy employed and i...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-15-188
更新日期:2014-06-14 00:00:00
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
更新日期:2007-07-23 00:00:00
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
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:In the last decade, there have been many applications of formal language theory in bioinformatics such as RNA structure prediction and detection of patterns in DNA. However, in the field of proteomics, the size of the protein alphabet and the complexity of relationship between amino acids have mainly limited...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-10-323
更新日期:2009-10-08 00:00:00
abstract:BACKGROUND:Genome imputation, admixture resolution and genome-wide association analyses are timely and computationally intensive processes with many composite and requisite steps. Analysis time increases further when building and installing the run programs required for these analyses. For scientists that may not be as...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-019-2964-5
更新日期:2019-06-28 00:00:00
abstract:BACKGROUND:The methodologies we use both enable and help define our research. However, as experimental complexity has increased the choice of appropriate methodologies has become an increasingly difficult task. This makes it difficult to keep track of available bioinformatics software, let alone the most suitable proto...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-9-359
更新日期:2008-09-01 00:00:00
abstract:BACKGROUND:Reverse transcription followed by real-time PCR is widely used for quantification of specific mRNA, and with the use of double-stranded DNA binding dyes it is becoming a standard for microarray data validation. Despite the kinetic information generated by real-time PCR, most popular analysis methods assume c...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-8-85
更新日期:2007-03-09 00:00:00
abstract:BACKGROUND:Visualization tools for deep learning models typically focus on discovering key input features without considering how such low level features are combined in intermediate layers to make decisions. Moreover, many of these methods examine a network's response to specific input examples that may be insufficien...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-019-2957-4
更新日期:2019-07-19 00:00:00
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
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Several features are known to correlate with the GC-content in the human genome, including recombination rate, gene density and distance to telomere. However, by testing for pairwise correlation only, it is impossible to distinguish direct associations from indirect ones and to distinguish between causes and...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-10-S1-S66
更新日期:2009-01-30 00:00:00
abstract:BACKGROUND:An important application of high dimensional gene expression measurements is the risk prediction and the interpretation of the variables in the resulting survival models. A major problem in this context is the typically large number of genes compared to the number of observations (individuals). Feature selec...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-12-478
更新日期:2011-12-16 00:00:00
abstract:BACKGROUND:Prostate carcinoma is among the most common types of cancer affecting hundreds of thousands people every year. Once the metastatic form of prostate carcinoma is documented, the majority of patients die from their tumors as opposed to other causes. The key to successful treatment is in the earliest possible d...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-10-S11-S6
更新日期:2009-10-08 00:00:00
abstract:BACKGROUND:RNA-Sequencing (RNA-seq) experiments have been popularly applied to transcriptome studies in recent years. Such experiments are still relatively costly. As a result, RNA-seq experiments often employ a small number of replicates. Power analysis and sample size calculation are challenging in the context of dif...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-016-0994-9
更新日期:2016-03-31 00:00:00
abstract:BACKGROUND:Throughout the metazoan lineage, typically gonadal expressed Piwi proteins and their guiding piRNAs (~26-32nt in length) form a protective mechanism of RNA interference directed against the propagation of transposable elements (TEs). Most piRNAs are generated from genomic piRNA clusters. Annotation of experi...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-13-5
更新日期:2012-01-10 00:00:00
abstract:BACKGROUND:Dihydrouridine (D) is a modified base found in conserved positions in the D-loop of tRNA in Bacteria, Eukaryota, and some Archaea. Despite the abundant occurrence of D, little is known about its biochemical roles in mediating tRNA function. It is assumed that D may destabilize the structure of tRNA and thus ...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-13-153
更新日期:2012-06-28 00:00:00
abstract:BACKGROUND:The Bioinformatics Resource Manager (BRM) is a web-based tool developed to facilitate identifier conversion and data integration for Homo sapiens (human), Mus musculus (mouse), Rattus norvegicus (rat), Danio rerio (zebrafish), and Macaca mulatta (macaque), as well as perform orthologous conversions among the...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-019-2805-6
更新日期:2019-05-17 00:00:00
abstract:BACKGROUND:The miRNAs, a class of short approximately 22-nucleotide non-coding RNAs, often act post-transcriptionally to inhibit mRNA expression. In effect, they control gene expression by targeting mRNA. They also help in carrying out normal functioning of a cell as they play an important role in various cellular proc...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-14-266
更新日期:2013-09-04 00:00:00
abstract:BACKGROUND:The most common method of identifying groups of functionally related genes in microarray data is to apply a clustering algorithm. However, it is impossible to determine which clustering algorithm is most appropriate to apply, and it is difficult to verify the results of any algorithm due to the lack of a gol...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-6-115
更新日期:2005-05-12 00:00:00
abstract:BACKGROUND:The amount of scientific information about MicroRNAs (miRNAs) is growing exponentially, making it difficult for researchers to interpret experimental results. In this study, we present an automated text mining approach using Latent Semantic Indexing (LSI) for prioritization, clustering and functional annotat...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-016-1223-2
更新日期:2016-10-06 00:00:00
abstract:BACKGROUND:The adaptive immune response intrinsically depends on hypervariable human leukocyte antigen (HLA) genes. Concomitantly, correct HLA phenotyping is crucial for successful donor-patient matching in organ transplantation. The cost and technical limitations of current laboratory techniques, together with advance...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-018-2239-6
更新日期:2018-06-25 00:00:00
abstract:BACKGROUND:Mechanistic models that describe the dynamical behaviors of biochemical systems are common in computational systems biology, especially in the realm of cellular signaling. The development of families of such models, either by a single research group or by different groups working within the same area, presen...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-15-316
更新日期:2014-09-25 00:00:00
abstract:BACKGROUND:The human immunodeficiency virus type 1 (HIV-1) aspartic protease is an important enzyme owing to its imperative part in viral development and a causative agent of deadliest disease known as acquired immune deficiency syndrome (AIDS). Development of HIV-1 protease inhibitors can help understand the specifici...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/s12859-016-1337-6
更新日期:2016-12-23 00:00:00
abstract:BACKGROUND:Microarray technology allows the analysis of genomic aberrations at an ever increasing resolution, making functional interpretation of these vast amounts of data the main bottleneck in routine implementation of high resolution array platforms, and emphasising the need for a centralised and easy to use CNV da...
journal_title:BMC bioinformatics
pub_type: 杂志文章
doi:10.1186/1471-2105-12-4
更新日期:2011-01-05 00:00:00
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
更新日期:2018-12-17 00:00:00