| 41. |
- de Weerd, Hendrik A., et al.
(författare)
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MODifieR : an ensemble R package for inference of disease modules from transcriptomics networks
- 2020
-
Ingår i: Bioinformatics. - : Oxford University Press. - 1367-4803 .- 1367-4811 .- 1460-2059. ; 36:12, s. 3918-3919
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Tidskriftsartikel (refereegranskat)abstract
- MOTIVATION: Complex diseases are due to the dense interactions of many disease-associated factors that dysregulate genes that in turn form so-called disease modules, which have shown to be a powerful concept for understanding pathological mechanisms. There exist many disease module inference methods that rely on somewhat different assumptions, but there is still no gold standard or best performing method. Hence, there is a need for combining these methods to generate robust disease modules.RESULTS: We developed MODule IdentiFIER (MODifieR), an ensemble R package of nine disease module inference methods from transcriptomics networks. MODifieR uses standardized input and output allowing the possibility to combine individual modules generated from these methods into more robust disease-specific modules, contributing to a better understanding of complex diseases.AVAILABILITY: MODifieR is available under the GNU GPL license and can be freely downloaded from https://gitlab.com/Gustafsson-lab/MODifieR and as a Docker image from https://hub.docker.com/r/ddeweerd/modifier.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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| 42. |
- Delhomme, Nicolas, et al.
(författare)
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easyRNASeq : a bioconductor package for processing RNA-Seq data.
- 2012
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 28:19
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Tidskriftsartikel (refereegranskat)abstract
- MOTIVATION: RNA sequencing is becoming a standard for expression profiling experiments and many tools have been developed in the past few years to analyze RNA-Seq data. Numerous 'Bioconductor' packages are available for next-generation sequencing data loading in R, e.g. ShortRead and Rsamtools as well as to perform differential gene expression analyses, e.g. DESeq and edgeR. However, the processing tasks lying in between these require the precise interplay of many Bioconductor packages, e.g. Biostrings, IRanges or external solutions are to be sought.RESULTS: We developed 'easyRNASeq', an R package that simplifies the processing of RNA sequencing data, hiding the complex interplay of the required packages behind a single functionality.AVAILABILITY: The package is implemented in R (as of version 2.15) and is available from Bioconductor (as of version 2.10) at the URL: http://bioconductor.org/packages/release/bioc/html/easyRNASeq.html, where installation and usage instructions can be found.CONTACT: delhomme@embl.de.
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| 43. |
- Demissie, Meaza, et al.
(författare)
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Unequal group variances in microarray data analyses
- 2008
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 24:9, s. 1168-1174
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: In searching for differentially expressed (DE) genes in microarray data, we often observe a fraction of the genes to have unequal variability between groups. This is not an issue in large samples, where a valid test exists that uses individual variances separately. The problem arises in the small-sample setting, where the approximately valid Welch test lacks sensitivity, while the more sensitive moderated t-test assumes equal variance. Methods: We introduce a moderated Welch test (MWT) that allows unequal variance between groups. It is based on (i) weighting of pooled and unpooled standard errors and (ii) improved estimation of the gene-level variance that exploits the information from across the genes. Results: When a non-trivial proportion of genes has unequal variability, false discovery rate (FDR) estimates based on the standard t and moderated t-tests are often too optimistic, while the standard Welch test has low sensitivity. The MWT is shown to (i) perform better than the standard t, the standard Welch and the moderated t-tests when the variances are unequal between groups and (ii) perform similarly to the moderated t, and better than the standard t and Welch tests when the group variances are equal. These results mean that MWT is more reliable than other existing tests over wider range of data conditions. Availability: R package to perform MWT is available at http://www.meb.ki.se/similar to yudpaw Contact: yudi.pawitan@ki.se Supplementary information: Supplementary data are available at Bioinformatics online.
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| 44. |
- Dessimoz, Christophe, et al.
(författare)
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Toward community standards in the quest for orthologs
- 2012
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 28:6, s. 900-904
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The identification of orthologs-genes pairs descended from a common ancestor through speciation, rather than duplication-has emerged as an essential component of many bioinformatics applications, ranging from the annotation of new genomes to experimental target prioritization. Yet, the development and application of orthology inference methods is hampered by the lack of consensus on source proteomes, file formats and benchmarks. The second 'Quest for Orthologs' meeting brought together stakeholders from various communities to address these challenges. We report on achievements and outcomes of this meeting, focusing on topics of particular relevance to the research community at large. The Quest for Orthologs consortium is an open community that welcomes contributions from all researchers interested in orthology research and applications.
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| 45. |
- Desvignes, Thomas, et al.
(författare)
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Unification of miRNA and isomiR research : the mirGFF3 format and the mirtop API
- 2020
-
Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 36:3, s. 698-703
-
Tidskriftsartikel (refereegranskat)abstract
- Motivation: MicroRNAs (miRNAs) are small RNA molecules (similar to 22 nucleotide long) involved in post-transcriptional gene regulation. Advances in high-throughput sequencing technologies led to the discovery of isomiRs, which are miRNA sequence variants. While many miRNA-seq analysis tools exist, the diversity of output formats hinders accurate comparisons between tools and precludes data sharing and the development of common downstream analysis methods. Results: To overcome this situation, we present here a community-based project, miRNA Transcriptomic Open Project (miRTOP) working towards the optimization of miRNA analyses. The aim of miRTOP is to promote the development of downstream isomiR analysis tools that are compatible with existing detection and quantification tools. Based on the existing GFF3 format, we first created a new standard format, mirGFF3, for the output of miRNA/isomiR detection and quantification results from small RNA-seq data. Additionally, we developed a command line Python tool, mirtop, to create and manage the mirGFF3 format. Currently, mirtop can convert into mirGFF3 the outputs of commonly used pipelines, such as seqbuster, isomiR-SEA, sRNAbench, Prost! as well as BAM files. Some tools have also incorporated the mirGFF3 format directly into their code, such as, miRge2.0, IsoMIRmap and OptimiR. Its open architecture enables any tool or pipeline to output or convert results into mirGFF3. Collectively, this isomiR categorization system, along with the accompanying mirGFF3 and mirtop API, provide a comprehensive solution for the standardization of miRNA and isomiR annotation, enabling data sharing, reporting, comparative analyses and benchmarking, while promoting the development of common miRNA methods focusing on downstream steps of miRNA detection, annotation and quantification.
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| 46. |
- Dib, L., et al.
(författare)
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Evolutionary footprint of coevolving positions in genes
- 2014
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 30:9, s. 1241-1249
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: The analysis of molecular coevolution provides information on the potential functional and structural implication of positions along DNA sequences, and several methods are available to identify coevolving positions using probabilistic or combinatorial approaches. The specific nucleotide or amino acid profile associated with the coevolution process is, however, not estimated, but only known profiles, such as the Watson-Crick constraint, are usually considered a priori in current measures of coevolution. Results: Here, we propose a new probabilistic model, Coev, to identify coevolving positions and their associated profile in DNA sequences while incorporating the underlying phylogenetic relationships. The process of coevolution is modeled by a 16 X 16 instantaneous rate matrix that includes rates of transition as well as a profile of coevolution. We used simulated, empirical and illustrative data to evaluate our model and to compare it with a model of `independent' evolution using Akaike Information Criterion. We showed that the Coev model is able to discriminate between coevolving and non-coevolving positions and provides better specificity and specificity than other available approaches. We further demonstrate that the identification of the profile of coevolution can shed new light on the process of dependent substitution during lineage evolution.
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| 47. |
- Dickinson, Q., et al.
(författare)
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Multi-omic integration by machine learning (MIMaL)
- 2022
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 38:21
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: Cells respond to environments by regulating gene expression to exploit resources optimally. Recent advances in technologies allow for measuring the abundances of RNA, proteins, lipids and metabolites. These highly complex datasets reflect the states of the different layers in a biological system. Multi-omics is the integration of these disparate methods and data to gain a clearer picture of the biological state. Multi-omic studies of the proteome and metabolome are becoming more common as mass spectrometry technology continues to be democratized. However, knowledge extraction through the integration of these data remains challenging. Results: Connections between molecules in different omic layers were discovered through a combination of machine learning and model interpretation. Discovered connections reflected protein control (ProC) over metabolites. Proteins discovered to control citrate were mapped onto known genetic and metabolic networks, revealing that these protein regulators are novel. Further, clustering the magnitudes of ProC over all metabolites enabled the prediction of five gene functions, each of which was validated experimentally. Two uncharacterized genes, YJR120W and YDL157C, were accurately predicted to modulate mitochondrial translation. Functions for three incompletely characterized genes were also predicted and validated, including SDH9, ISC1 and FMP52. A website enables results exploration and also MIMaL analysis of user-supplied multi-omic data.
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| 48. |
- Dimou, Niki L., et al.
(författare)
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GWAR : robust analysis and meta-analysis of genome-wide association studies
- 2017
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 33:10, s. 1521-1527
-
Tidskriftsartikel (refereegranskat)abstract
- Motivation: In the context of genome-wide association studies (GWAS), there is a variety of statistical techniques in order to conduct the analysis, but, in most cases, the underlying genetic model is usually unknown. Under these circumstances, the classical Cochran-Armitage trend test (CATT) is suboptimal. Robust procedures that maximize the power and preserve the nominal type I error rate are preferable. Moreover, performing a meta-analysis using robust procedures is of great interest and has never been addressed in the past. The primary goal of this work is to implement several robust methods for analysis and meta-analysis in the statistical package Stata and subsequently to make the software available to the scientific community. Results: The CATT under a recessive, additive and dominant model of inheritance as well as robust methods based on the Maximum Efficiency Robust Test statistic, the MAX statistic and the MIN2 were implemented in Stata. Concerning MAX and MIN2, we calculated their asymptotic null distributions relying on numerical integration resulting in a great gain in computational time without losing accuracy. All the aforementioned approaches were employed in a fixed or a random effects meta-analysis setting using summary data with weights equal to the reciprocal of the combined cases and controls. Overall, this is the first complete effort to implement procedures for analysis and meta-analysis in GWAS using Stata.
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| 49. |
- Draminski, Michal, et al.
(författare)
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Monte Carlo feature selection for supervised classification
- 2008
-
Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 24:1, s. 110-117
-
Tidskriftsartikel (refereegranskat)abstract
- MOTIVATION: Pre-selection of informative features for supervised classification is a crucial, albeit delicate, task. It is desirable that feature selection provides the features that contribute most to the classification task per se and which should therefore be used by any classifier later used to produce classification rules. In this article, a conceptually simple but computer-intensive approach to this task is proposed. The reliability of the approach rests on multiple construction of a tree classifier for many training sets randomly chosen from the original sample set, where samples in each training set consist of only a fraction of all of the observed features. RESULTS: The resulting ranking of features may then be used to advantage for classification via a classifier of any type. The approach was validated using Golub et al. leukemia data and the Alizadeh et al. lymphoma data. Not surprisingly, we obtained a significantly different list of genes. Biological interpretation of the genes selected by our method showed that several of them are involved in precursors to different types of leukemia and lymphoma rather than being genes that are common to several forms of cancers, which is the case for the other methods.
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| 50. |
- Duchemin, Wandrille, et al.
(författare)
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RecPhyloXML : a format for reconciled gene trees
- 2018
-
Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 34:21, s. 3646-3652
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: A reconciliation is an annotation of the nodes of a gene tree with evolutionary events-for example, speciation, gene duplication, transfer, loss, etc. -along with a mapping onto a species tree. Many algorithms and software produce or use reconciliations but often using different reconciliation formats, regarding the type of events considered or whether the species tree is dated or not. This complicates the comparison and communication between different programs. Results: Here, we gather a consortium of software developers in gene tree species tree reconciliation to propose and endorse a format that aims to promote an integrative-albeit flexible-specification of phylogenetic reconciliations. This format, named recPhyloXML, is accompanied by several tools such as a reconciled tree visualizer and conversion utilities.
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