| 1. |
- Abdel-Rehim, Abbi, et al.
(författare)
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Protein-ligand binding affinity prediction exploiting sequence constituent homology
- 2023
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Ingår i: Bioinformatics. - 1367-4803 .- 1367-4811. ; 39:8
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Tidskriftsartikel (refereegranskat)abstract
- MOTIVATION: Molecular docking is a commonly used approach for estimating binding conformations and their resultant binding affinities. Machine learning has been successfully deployed to enhance such affinity estimations. Many methods of varying complexity have been developed making use of some or all the spatial and categorical information available in these structures. The evaluation of such methods has mainly been carried out using datasets from PDBbind. Particularly the Comparative Assessment of Scoring Functions (CASF) 2007, 2013, and 2016 datasets with dedicated test sets. This work demonstrates that only a small number of simple descriptors is necessary to efficiently estimate binding affinity for these complexes without the need to know the exact binding conformation of a ligand. RESULTS: The developed approach of using a small number of ligand and protein descriptors in conjunction with gradient boosting trees demonstrates high performance on the CASF datasets. This includes the commonly used benchmark CASF2016 where it appears to perform better than any other approach. This methodology is also useful for datasets where the spatial relationship between the ligand and protein is unknown as demonstrated using a large ChEMBL-derived dataset. AVAILABILITY AND IMPLEMENTATION: Code and data uploaded to https://github.com/abbiAR/PLBAffinity.
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| 2. |
- Afkham, Heydar Maboudi, et al.
(författare)
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Uncertainty estimation of predictions of peptides' chromatographic retention times in shotgun proteomics
- 2017
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Ingår i: Bioinformatics. - : OXFORD UNIV PRESS. - 1367-4803 .- 1367-4811. ; 33:4, s. 508-513
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: Liquid chromatography is frequently used as a means to reduce the complexity of peptide-mixtures in shotgun proteomics. For such systems, the time when a peptide is released from a chromatography column and registered in the mass spectrometer is referred to as the peptide's retention time. Using heuristics or machine learning techniques, previous studies have demonstrated that it is possible to predict the retention time of a peptide from its amino acid sequence. In this paper, we are applying Gaussian Process Regression to the feature representation of a previously described predictor ELUDE. Using this framework, we demonstrate that it is possible to estimate the uncertainty of the prediction made by the model. Here we show how this uncertainty relates to the actual error of the prediction. Results: In our experiments, we observe a strong correlation between the estimated uncertainty provided by Gaussian Process Regression and the actual prediction error. This relation provides us with new means for assessment of the predictions. We demonstrate how a subset of the peptides can be selected with lower prediction error compared to the whole set. We also demonstrate how such predicted standard deviations can be used for designing adaptive windowing strategies.
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| 3. |
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| 4. |
- Ameur, Adam, et al.
(författare)
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The LCB Data Warehouse
- 2006
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 22:8, s. 1024-1026
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Tidskriftsartikel (refereegranskat)abstract
- The Linnaeus Centre for Bioinformatics Data Warehouse (LCB-DWH) is a web-based infrastructure for reliable and secure microarray gene expression data management and analysis that provides an online service for the scientific community. The LCB-DWH is an effort towards a complete system for storage (using the BASE system), analysis and publication of microarray data. Important features of the system include: access to established methods within R/Bioconductor for data analysis, built-in connection to the Gene Ontology database and a scripting facility for automatic recording and re-play of all the steps of the analysis. The service is up and running on a high performance server. At present there are more than 150 registered users.
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| 5. |
- 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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| 6. |
- Andersson, Alma, et al.
(författare)
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sepal : identifying transcript profiles with spatial patterns by diffusion-based modeling
- 2021
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811 .- 1460-2059. ; 37:17, s. 2644-2650
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: Collection of spatial signals in large numbers has become a routine task in multiple omics-fields, but parsing of these rich datasets still pose certain challenges. In whole or near-full transcriptome spatial techniques, spurious expression profiles are intermixed with those exhibiting an organized structure. To distinguish profiles with spatial patterns from the background noise, a metric that enables quantification of spatial structure is desirable. Current methods designed for similar purposes tend to be built around a framework of statistical hypothesis testing, hence we were compelled to explore a fundamentally different strategy. Results: We propose an unexplored approach to analyze spatial transcriptomics data, simulating diffusion of individual transcripts to extract genes with spatial patterns. The method performed as expected when presented with synthetic data. When applied to real data, it identified genes with distinct spatial profiles, involved in key biological processes or characteristic for certain cell types. Compared to existing methods, ours seemed to be less informed by the genes' expression levels and showed better time performance when run with multiple cores.
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| 7. |
- Andersson, Robin, et al.
(författare)
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A Segmental Maximum A Posteriori Approach to Genome-wide Copy Number Profiling
- 2008
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 24:6, s. 751-758
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- MOTIVATION: Copy number profiling methods aim at assigning DNA copy numbers to chromosomal regions using measurements from microarray-based comparative genomic hybridizations. Among the proposed methods to this end, Hidden Markov Model (HMM)-based approaches seem promising since DNA copy number transitions are naturally captured in the model. Current discrete-index HMM-based approaches do not, however, take into account heterogeneous information regarding the genomic overlap between clones. Moreover, the majority of existing methods are restricted to chromosome-wise analysis. RESULTS: We introduce a novel Segmental Maximum A Posteriori approach, SMAP, for DNA copy number profiling. Our method is based on discrete-index Hidden Markov Modeling and incorporates genomic distance and overlap between clones. We exploit a priori information through user-controllable parameterization that enables the identification of copy number deviations of various lengths and amplitudes. The model parameters may be inferred at a genome-wide scale to avoid overfitting of model parameters often resulting from chromosome-wise model inference. We report superior performances of SMAP on synthetic data when compared with two recent methods. When applied on our new experimental data, SMAP readily recognizes already known genetic aberrations including both large-scale regions with aberrant DNA copy number and changes affecting only single features on the array. We highlight the differences between the prediction of SMAP and the compared methods and show that SMAP accurately determines copy number changes and benefits from overlap consideration.
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| 8. |
- Andersson, Siv G E, et al.
(författare)
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Comparative genomics of microbial pathogens and symbionts.
- 2002
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Ingår i: Bioinformatics. - 1367-4803 .- 1367-4811. ; 18 Suppl 2, s. S17-
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Tidskriftsartikel (refereegranskat)abstract
- We are interested in quantifying the contribution of gene acquisition, loss, expansion and rearrangements to the evolution of microbial genomes. Here, we discuss factors influencing microbial genome divergence based on pair-wise genome comparisons of closely related strains and species with different lifestyles. A particular focus is on intracellular pathogens and symbionts of the genera Rickettsia, Bartonella and BUCHNERA: Extensive gene loss and restricted access to phage and plasmid pools may provide an explanation for why single host pathogens are normally less successful than multihost pathogens. We note that species-specific genes tend to be shorter than orthologous genes, suggesting that a fraction of these may represent fossil-orfs, as also supported by multiple sequence alignments among species. The results of our genome comparisons are placed in the context of phylogenomic analyses of alpha and gamma proteobacteria. We highlight artefacts caused by different rates and patterns of mutations, suggesting that atypical phylogenetic placements can not a priori be taken as evidence for horizontal gene transfer events. The flexibility in genome structure among free-living microbes contrasts with the extreme stability observed for the small genomes of aphid endosymbionts, in which no rearrangements or inflow of genetic material have occurred during the past 50 millions years (1). Taken together, the results suggest that genomic stability correlate with the content of repeated sequences and mobile genetic elements, and thereby indirectly with bacterial lifestyles.
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| 9. |
- Anil, Anandashankar, et al.
(författare)
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HiCapTools : a software suite for probe design and proximity detection for targeted chromosome conformation capture applications
- 2018
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Ingår i: Bioinformatics. - : OXFORD UNIV PRESS. - 1367-4803 .- 1367-4811. ; 34:4, s. 675-677
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Tidskriftsartikel (refereegranskat)abstract
- Folding of eukaryotic genomes within nuclear space enables physical and functional contacts between regions that are otherwise kilobases away in sequence space. Targeted chromosome conformation capture methods (T2C, chi-C and HiCap) are capable of informing genomic contacts for a subset of regions targeted by probes. We here present HiCapTools, a software package that can design sequence capture probes for targeted chromosome capture applications and analyse sequencing output to detect proximities involving targeted fragments. Two probes are designed for each feature while avoiding repeat elements and non-unique regions. The data analysis suite processes alignment files to report genomic proximities for each feature at restriction fragment level and is isoform-aware for gene features. Statistical significance of contact frequencies is evaluated using an empirically derived background distribution. Targeted chromosome conformation capture applications are invaluable for locating target genes of disease-associated variants found by genome-wide association studies. Hence, we believe our software suite will prove to be useful for a wider user base within clinical and functional applications.
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| 10. |
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