Chair of Bioinformatics

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View all other units

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Head of the Chair: prof. Maido Remm
Contact: Riia 23b-525, Phone: 737 5001, email: maido.remm [ät] ut.ee

Teaching
Chair of Bioinformatics conducts teaching of the following subjects (overall 23 EAP).
3 EAP     LOMR.10.002    Bioinformatics I (bachelor level)
3 EAP     LOMR.10.005    Bioinformatics II (bachelor level)
3 EAP    LOMR.10.007    Data Analysis in Molecular Biology (bachelor level)
6 EAP    LOMR.10.008    Sequence Analysis in Linux environment
6 EAP    LTMR.10.001    Genomics and Bioinformatics (Science and Technology, bachelor level)
2 EAP    LTTI.00.012    Laboratory Projects (Science and Technology, bachelor level)

Research areas
1. Computational analysis of bacterial genomes and prediction of antimicrobial resistance.
2. Development of diagnostic tests based on DNA sequence.
3. Development of fast and original computational methods for analysis of personal genomes.

Research

1. Computational analysis of bacterial genomes and prediction of antimicrobial resistance.
We develop computational tools for automated analysis of bacterial genome sequences. This includes assembly, validation of species, check and elimination of contamination by other species, determination of MLST type, building a phylogenetic tree from core genome sequences, detecting the presence and intactness of known resistance genes, detecting and describing the context of resistance genes, detection and description of plasmid sequences. Some of the tools for this analysis have been developed earlier in our workgroup, e.g. StrainSeeker (Roosaare et al., 2017), PlasmidSeeker (Roosaare et al., 2018) and PhenotypeSeeker (Aun et al., 2018).

Large-scale analysis of bacterial genomes can be done with different purposes. The most common aim is the epidemiological analysis of the spread of bacterial strains or their resistance genes (Telling et al., 2018; Bilozor et al., 2019; Sepp et al., 2019; Telling et al., 2020, Aun et al., 2021).
Second frequent aim of bacterial genome analysis is a functional analysis of genomic variants that appear under strong natural selection in a certain environment. A good example of this kind of analysis is the paper by Jõers et al., 2019, where we describe which genes are mutated in a strain that is less responsive to muropeptides in the environment.

Currently, our group is actively working towards developing statistical prediction models that would predict virulence, antimicrobial resistance or other properties of bacterial strains, based on their sequence. For this, we use machine learning methods combined with biological knowledge. Currently, we have working models for predicting the resistance in 16 bacterial species against more than 20 antimicrobial substances. We have developed a web-based tool PhenotypeSeeker for using these models.

2. Development of diagnostic tests based on DNA sequence.
For more than 10 years we have been studying how DNA molecules hybridize to their specific and non-specific targets. This is important for designing highly specific PCR primers or microarray probes. We have written several software packages facilitating genomic PCR primer design. Our workgroup has participated in the development of widely used Primer3 software and we host an official webpage for Primer3.

We have implemented our theoretical knowledge in practice in form of various DNA-based molecular tests. For example, we have developed diagnostic tests for respiratory disease pathogen detection for Estonian company Quattromed HTI (currently part of SynLab Eesti), blood sepsis-related pathogen tests for Dutch start-up company Microbiome Ltd (van den Brand et al., 2014) and food allergen detection test for Estonian biotech company Icosagen Ltd. Currently, we develop multiplex PCR tests that would enable faster detection of sequence types of food pathogen Listeria monocytogenes.

Looking at a longer perspective we have started to develop novel diagnostic tests, based on next-generation sequencing data. A large advantage of DNA sequencing tests over PCR-based tests is that it can detect all pathogens simultaneously, unlike PCR that can detect only one pathogen per primer pair. Our focus in developing sequencing-based tests is in developing software and databases for the detection of pathogenic or allergenic species or strains. Good examples of such software are described in papers Raime and Remm, 2018 and Raime et al., 2020. In these papers, we described methods and proof-of-principle tests for the detection of potentially allergenic food components using food sequencing approach.

3. Development of fast and original computational methods for the analysis of personal genomes.
Within the last five years, we have developed several novels and fast methods for the detection of single nucleotide variants (SNV) from human personal genomes. FastGT (Pajuste et al., 2017) finds genotypes of all previously known SNV-s in a given personal genome in only 30 minutes. KATK finds all SNVs (known and novel from personal genomes in 3 hours (Kaplinski et al., preprint). In addition, we develop algorithms for detection of structural variants, that are frequently neglected in GWAS analyses. For example, we can detect polymorphic Alu element insertion sites (Puurand et al., 2019), gene copy numbers (for example amylase gene copy numbers) and copy numbers of variable number tandem repeats e.g. those in front of ACAN, MAO, TRIB3 genes (Örd et al., 2020).
Our algorithms use a completely original approach to sequence analysis and this allows us to process human personal genomes ca 30 faster than traditional methods, without losing accuracy. Speed of the software is crucial in large scale analysis of individual genomes.

Selected publications

Kaplinski L, Möls M, Puurand T, Pajuste FD, Remm M (2020). KATK: fast genotyping of rare variants directly from unmapped sequencing reads. bioRxiv. https://doi.org/10.1101/2020.12.23.424124. [Full text]
Raime K, Krjutškov K and Remm M. (2020). Method for the Identification of Plant DNA in Food Using Alignment-Free Analysis of Sequencing Reads: A Case Study on Lupin. Front. Plant Sci., 11:646. [Full text]
Örd T, Puurand T, Örd D, Annilo T, Möls M, Remm M and Örd T. (2020). A human-specific VNTR in the TRIB3 promoter causes gene expression variation between individuals. PLoS Genet., 16(8):e1008981. [Full text]
Telling K, Brauer A, Laht M, Kalmus P, Toompere K, Kisand V, Maimets, M, Remm M, Tenson T and Lutsar I. (2020). Characteristics of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae and Contact to Animals in Estonia. Microorganisms, 8:1130. [Full text]
Puurand T, Kukuškina V, Pajuste FD and Remm M. (2019). AluMine: alignment-free method for the discovery of polymorphic Alu element insertions. Mobile DNA, 10:31. [Full text]
Sepp E, Andreson R, Balode A, Bilozor A, Brauer A, Egorova S, Huik K, Ivanova M, Kaftyreva L, Kõljalg S, Kõressaar T, Makarova M, Miciuleviciene J, Pai K, Remm M, Rööp T, Naaber P. (2019). Phenotypic and Molecular Epidemiology of ESBL-, AmpC-, and Carbapenemase-Producing Escherichia coli in Northern and Eastern Europe. Front Microbiol., 10:2465. [Full text]
Bilozor A, Balode A, Chakhunashvili G, Chumachenko T, Egorova S, Ivanova M, Kaftyreva L, Kõljalg S, Kõressaar T, Lysenko O, Miciuleviciene J, Mändar R, Lis DO, Wesolowska MP, Ratnik K, Remm M, Rudzko J, Rööp T, Saule M, Sepp E, Shyshporonok J, Titov L, Tsereteli D, Naaber P. (2019). Application of Molecular Methods for Carbapenemase Detection. Front Microbiol., 10:1755. [Full text]
Aun E, Brauer A, Kisand V, Tenson T and Remm M. (2018). A k-mer-based method for the identification of phenotype-associated genomic biomarkers and predicting phenotypes of sequenced bacteria. PLoS Computational Biology, 14(10):e1006434. [Full text]
Telling K, Laht M, Brauer A, Remm M, Kisand V, Maimets M, Tenson T and Lutsar I. (2018). Multidrug resistant Pseudomonas aeruginosa in Estonian hospitals. BMC Infect Dis., 18(1): 513. [Full text]
Roosaare M, Puustusmaa M, Möls M, Vaher M, and Remm M. (2018). PlasmidSeeker: identification of known plasmids from bacterial whole genome sequencing reads. PeerJ, 6: e4588. [Full Text]
Sauk M, Žilina O, Kurg A, Ustav EL, Peters M, Paluoja P, Roost AM, Teder H, Palta P, Brison N, Vermeesch JR, Krjutškov K, Salumets A and Kaplinski L. (2018). NIPTmer: rapid k-mer-based software package for detection of fetal aneuploidies. Scientific Reports, 8(1):5616. [Full Text]
Raime K and Remm M. (2018). Method for the Identification of Taxon-Specific k-mers from Chloroplast Genome: A Case Study on Tomato Plant (Solanum lycopersicum). Frontiers in Plant Science, 9: 6. [Full Text]
Kõressaar T, Lepamets M, Kaplinski L, Raime K, Andreson R and Remm M. (2018). Primer3_masker: integrating masking of template sequence with primer design software. Bioinformatics, 34:1937–1938. [Full text]
Pajuste FD, Kalpinski L, Möls M, Puurand T, Lepamets M, Remm M. (2017). FastGT: an alignment-free method for calling common SNVs directly from raw sequencing reads. Scientific Reports, 7:2537 [Full Text]
Roosaare M, Vaher M, Kaplinski L, Möls M, Andreson R, Lepamets M, Kõressaar T, Naaber P, Kõljalg S, Remm M. (2017). StrainSeeker: fast identification of bacterial strains from raw sequencing reads using user-provided guide trees. PeerJ, 5: e3353. [Full Text]
Van den Brand M, Peters RP, Catsburg A, Rubenjan A, Broeke FJ, van den Dungen FA, van Weissenbruch MM, van Furth AM, Kõressaar T, Remm M, Savelkoul PH, Bos MP. (2014). Development of a multiplex real-time PCR assay for the rapid diagnosis of neonatal late onset sepsis. Journal of Microbiological Methods, 106C:8-15 [Full Text].

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Chair of Bioinformatics