| 1. |
- Michel, Mirco, et al.
(författare)
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Predicting accurate contacts in thousands of Pfam domain families using PconsC3
- 2017
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 33:18, s. 2859-2866
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: A few years ago it was shown that by using a maximum entropy approach to describe couplings between columns in a multiple sequence alignment it is possible to significantly increase the accuracy of residue contact predictions. For very large protein families with more than 1000 effective sequences the accuracy is sufficient to produce accurate models of proteins as well as complexes. Today, for about half of all Pfam domain families no structure is known, but unfortunately most of these families have at most a few hundred members, i.e. are too small for such contact prediction methods. Results: To extend accurate contact predictions to the thousands of smaller protein families we present PconsC3, a fast and improved method for protein contact predictions that can be used for families with even 100 effective sequence members. PconsC3 outperforms direct coupling analysis (DCA) methods significantly independent on family size, secondary structure content, contact range, or the number of selected contacts. Availability and implementation: PconsC3 is available as a web server and downloadable version at http://c3.pcons.net. The downloadable version is free for all to use and licensed under the GNU General Public License, version 2. At this site contact predictions for most Pfam families are also available. We do estimate that more than 4000 contact maps for Pfam families of unknown structure have more than 50% of the top-ranked contacts predicted correctly. Contact: arne@bioinfo.se Supplementary information: Supplementary data are available at Bioinformatics online.
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| 2. |
- Moore, J. Harry, et al.
(författare)
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Icolos: a workflow manager for structure-based post-processing of de novo generated small molecules
- 2022
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 38:21, s. 4951-4952
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Tidskriftsartikel (refereegranskat)abstract
- A Summary: We present Icolos, a workflow manager written in Python as a tool for automating complex structure-based workflows for drug design. Icolos can be used as a standalone tool, for example in virtual screening campaigns, or can be used in conjunction with deep learning-based molecular generation facilitated for example by REINVENT, a previously published molecular de novo design package. In this publication, we focus on the internal structure and general capabilities of Icolos, using molecular docking experiments as an illustrative example.
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| 3. |
- Andersson, Anders, et al.
(författare)
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Dual-genome primer design for construction of DNA microarrays
- 2005
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 21:3, s. 325-332
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: Microarray experiments using probes covering a whole transcriptome are expensive to initiate, and a major part of the costs derives from synthesizing gene-specific PCR primers or hybridization probes. The high costs may force researchers to limit their studies to a single organism, although comparing gene expression in different species would yield valuable information. Results: We have developed a method, implemented in the software DualPrime, that reduces the number of primers required to amplify the genes of two different genomes. The software identifies regions of high sequence similarity, and from these regions selects PCR primers shared between the genomes, such that either one or, preferentially, both primers in a given PCR can be used for amplification from both genomes. To assure high microarray probe specificity, the software selects primer pairs that generate products of low sequence similarity to other genes within the same genome. We used the software to design PCR primers for 2182 and 1960 genes from the hyperthermophilic archaea Sulfolobus solfataricus and Sulfolobus acidocaldarius, respectively. Primer pairs were shared among 705 pairs of genes, and single primers were shared among 1184 pairs of genes, resulting in a saving of 31% compared to using only unique primers. We also present an alternative primer design method, in which each gene shares primers with two different genes of the other genome, enabling further savings.
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| 4. |
- 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
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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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| 5. |
- Duchemin, Wandrille, et al.
(författare)
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RecPhyloXML : a format for reconciled gene trees
- 2018
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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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| 6. |
- Eriksson, Olivia, et al.
(författare)
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Uncertainty quantification, propagation and characterization by Bayesian analysis combined with global sensitivity analysis applied to dynamical intracellular pathway models
- 2019
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 35:2, s. 284-292
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: Dynamical models describing intracellular phenomena are increasing in size and complexity as more information is obtained from experiments. These models are often over-parameterized with respect to the quantitative data used for parameter estimation, resulting in uncertainty in the individual parameter estimates as well as in the predictions made from the model. Here we combine Bayesian analysis with global sensitivity analysis (GSA) in order to give better informed predictions; to point out weaker parts of the model that are important targets for further experiments, as well as to give guidance on parameters that are essential in distinguishing different qualitative output behaviours.Results: We used approximate Bayesian computation (ABC) to estimate the model parameters from experimental data, as well as to quantify the uncertainty in this estimation (inverse uncertainty quantification), resulting in a posterior distribution for the parameters. This parameter uncertainty was next propagated to a corresponding uncertainty in the predictions (forward uncertainty propagation), and a GSA was performed on the predictions using the posterior distribution as the possible values for the parameters. This methodology was applied on a relatively large model relevant for synaptic plasticity, using experimental data from several sources. We could hereby point out those parameters that by themselves have the largest contribution to the uncertainty of the prediction as well as identify parameters important to separate between qualitatively different predictions. This approach is useful both for experimental design as well as model building.
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| 7. |
- Ewels, Philip, et al.
(författare)
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MultiQC : summarize analysis results for multiple tools and samples in a single report
- 2016
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 32:19, s. 3047-3048
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: Fast and accurate quality control is essential for studies involving next-generation sequencing data. Whilst numerous tools exist to quantify QC metrics, there is no common approach to flexibly integrate these across tools and large sample sets. Assessing analysis results across an entire project can be time consuming and error prone; batch effects and outlier samples can easily be missed in the early stages of analysis.Results: We present MultiQC, a tool to create a single report visualising output from multiple tools across many samples, enabling global trends and biases to be quickly identified. MultiQC can plot data from many common bioinformatics tools and is built to allow easy extension and customization.
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| 8. |
- Garg, Shilpa, et al.
(författare)
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Read-based phasing of related individuals
- 2016
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 32:12, s. 234-242
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: Read-based phasing deduces the haplotypes of an individual from sequencing reads that cover multiple variants, while genetic phasing takes only genotypes as input and applies the rules of Mendelian inheritance to infer haplotypes within a pedigree of individuals. Combining both into an approach that uses these two independent sources of information-reads and pedigree-has the potential to deliver results better than each individually. Results: We provide a theoretical framework combining read-based phasing with genetic haplotyping, and describe a fixed-parameter algorithm and its implementation for finding an optimal solution. We show that leveraging reads of related individuals jointly in this way yields more phased variants and at a higher accuracy than when phased separately, both in simulated and real data. Coverages as low as 2 x for each member of a trio yield haplotypes that are as accurate as when analyzed separately at 15 x coverage per individual.
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| 9. |
- Haider, Christian, et al.
(författare)
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TreeDom : a graphical web tool for analysing domain architecture evolution
- 2016
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 32:15, s. 2384-2385
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Tidskriftsartikel (refereegranskat)abstract
- We present TreeDom, a web tool for graphically analysing the evolutionary history of domains in multi-domain proteins. Individual domains on the same protein chain may have distinct evolutionary histories, which is important to grasp in order to understand protein function. For instance, it may be important to know whether a domain was duplicated recently or long ago, to know the origin of inserted domains, or to know the pattern of domain loss within a protein family. TreeDom uses the Pfam database as the source of domain annotations, and displays these on a sequence tree. An advantage of TreeDom is that the user can limit the analysis to N sequences that are most similar to a query, or provide a list of sequence IDs to include. Using the Pfam alignment of the selected sequences, a tree is built and displayed together with the domain architecture of each sequence.
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| 10. |
- Höhna, Sebastian, et al.
(författare)
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TESS : an R package for efficiently simulating phylogenetic trees and performing Bayesian inference of lineage diversification rates
- 2016
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 32:5, s. 789-791
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Tidskriftsartikel (refereegranskat)abstract
- Many fundamental questions in evolutionary biology entail estimating rates of lineage diversification (speciation-extinction) that are modeled using birth-death branching processes. We leverage recent advances in branching-process theory to develop a flexible Bayesian framework for specifying diversification models-where rates are constant, vary continuously, or change episodically through time-and implement numerical methods to estimate parameters of these models from molecular phylogenies, even when species sampling is incomplete. We enable both statistical inference and efficient simulation under these models. We also provide robust methods for comparing the relative and absolute fit of competing branching-process models to a given tree, thereby providing rigorous tests of biological hypotheses regarding patterns and processes of lineage diversification.
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