Docent i datalogi. Forskar i beräkningsbiologi, främst evolution och jämförande genomik.
Jag är huvudsakligen inblandad i följande kurser:
- DA2004 Programmeringsteknik för matematiker
- DA3018 Datalogi för matematiker
- DA4001 Databasteknik
- DA4002 Mjukvaruutveckling
I urval från Stockholms universitets publikationsdatabas
2017. Raja H. Ali (et al.). BMC Bioinformatics 18Artikel
Background: MCMC-based methods are important for Bayesian inference of phylogeny and related parameters. Although being computationally expensive, MCMC yields estimates of posterior distributions that are useful for estimating parameter values and are easy to use in subsequent analysis. There are, however, sometimes practical difficulties with MCMC, relating to convergence assessment and determining burn-in, especially in large-scale analyses. Currently, multiple software are required to perform, e.g., convergence, mixing and interactive exploration of both continuous and tree parameters.
Results: We have written a software called VMCMC to simplify post-processing of MCMC traces with, for example, automatic burn-in estimation. VMCMC can also be used both as a GUI-based application, supporting interactive exploration, and as a command-line tool suitable for automated pipelines.
Conclusions: VMCMC is a free software available under the New BSD License. Executable jar files, tutorial manual and source code can be downloaded from https://bitbucket. org/rhali/visualmcmc/.
Assembly scaffolding with PE-contaminated mate-pair libraries
2016. Kristoffer Sahlin, Rayan Chikhi, Lars Arvestad. Bioinformatics 32 (13), 1925-1932Artikel
Motivation: Scaffolding is often an essential step in a genome assembly process, in which contigs are ordered and oriented using read pairs from a combination of paired-end libraries and longer-range mate-pair libraries. Although a simple idea, scaffolding is unfortunately hard to get right in practice. One source of problems is so-called PE-contamination in mate-pair libraries, in which a non-negligible fraction of the read pairs get the wrong orientation and a much smaller insert size than what is expected. This contamination has been discussed before, in relation to integrated scaffolders, but solutions rely on the orientation being observable, e.g. by finding the junction adapter sequence in the reads. This is not always possible, making orientation and insert size of a read pair stochastic. To our knowledge, there is neither previous work on modeling PE-contamination, nor a study on the effect PE-contamination has on scaffolding quality. Results: We have addressed PE-contamination in an update to our scaffolder BESST. We formulate the problem as an integer linear program which is solved using an efficient heuristic. The new method shows significant improvement over both integrated and stand-alone scaffolders in our experiments. The impact of modeling PE-contamination is quantified by comparing with the previous BESST model. We also show how other scaffolders are vulnerable to PE-contaminated libraries, resulting in an increased number of misassemblies, more conservative scaffolding and inflated assembly sizes.
BESST - Efficient scaffolding of large fragmented assemblies
2014. Kristoffer Sahlin (et al.). BMC Bioinformatics 15Artikel
The use of short reads from High Throughput Sequencing (HTS) techniques is now commonplace in de novo assembly. Yet, obtaining contiguous assemblies from short reads is challenging, thus making scaffolding an important step in the assembly pipeline. Different algorithms have been proposed but many of them use the number of read pairs supporting a linking of two contigs as an indicator of reliability. This reasoning is intuitive, but fails to account for variation in link count due to contig features.
We have also noted that published scaffolders are only evaluated on small datasets using output from only one assembler. Two issues arise from this. Firstly, some of the available tools are not well suited for complex genomes. Secondly, these evaluations provide little support for inferring a software’s general performance.
We propose a new algorithm, implemented in a tool called BESST, which can scaffold genomes of all sizes and complexities and was used to scaffold the genome of P. abies (20 Gbp). We performed a comprehensive comparison of BESST against the most popular stand-alone scaffolders on a large variety of datasets. Our results confirm that some of the popular scaffolders are not practical to run on complex datasets. Furthermore, no single stand-alone scaffolder outperforms the others on all datasets. However, BESST fares favorably to the other tested scaffolders on GAGE datasets and, moreover, outperforms the other methods when library insert size distribution is wide.
We conclude from our results that information sources other than the quantity of links, as is commonly used, can provide useful information about genome structure when scaffolding.
Quantitative synteny scoring improves homology inference and partitioning of gene families
2013. Raja Hashim Ali (et al.). BMC Bioinformatics 14 (Suppl,15), S12Artikel
Clustering sequences into families has long been an important step in characterization of genes and proteins. There are many algorithms developed for this purpose, most of which are based on either direct similarity between gene pairs or some sort of network structure, where weights on edges of constructed graphs are based on similarity. However, conserved synteny is an important signal that can help distinguish homology and it has not been utilized to its fullest potential.
Here, we present GenFamClust, a pipeline that combines the network properties of sequence similarity and synteny to assess homology relationship and merge known homologs into groups of gene families. GenFamClust identifies homologs in a more informed and accurate manner as compared to similarity based approaches. We tested our method against the Neighborhood Correlation method on two diverse datasets consisting of fully sequenced genomes of eukaryotes and synthetic data.
The results obtained from both datasets confirm that synteny helps determine homology and GenFamClust improves on Neighborhood Correlation method. The accuracy as well as the definition of synteny scores is the most valuable contribution of GenFamClust.
2013. Mehmood Alam Khan (et al.). BMC Bioinformatics 14, 334Artikel
BACKGROUND: Distance methods are ubiquitous tools in phylogenetics.Their primary purpose may be to reconstructevolutionary history, but they are also used as components in bioinformatic pipelines. However, poorcomputational efficiency has been a constraint on the applicability of distance methods on very largeproblem instances.
RESULTS: We present fastphylo, a software package containing implementations of efficient algorithms for twocommon problems in phylogenetics: estimating DNA/protein sequence distances and reconstructing aphylogeny from a distance matrix. We compare fastphylo with other neighbor joining based methodsand report the results in terms of speed and memory efficiency.
CONCLUSIONS: Fastphylo is a fast, memory efficient, and easy to use software suite. Due to its modular architecture,fastphylo is a flexible tool for many phylogenetic studies.
Visa alla publikationer av Lars Arvestad vid Stockholms universitet