- Thomas Sicheritz-Pontén, Professor, M.Sc., fil.dr is heading the Metagenomics group at the Center for Biological Sequ... moreThomas Sicheritz-Pontén, Professor, M.Sc., fil.dr is heading the Metagenomics group at the Center for Biological Sequence Analysis (CBS) at Department of Systems Biology. He has a background in Bioinformatics and Molecular Evolution from Uppsala University, Sweden and has been working in the genome/metagenome sequencing field for over 15 years, starting 1996 when he built the bioinformatics infrastructure for the first published Scandinavian genome project. His primary interests are microbial genome analysis, metagenomics, antique systems biology, marine biotechnology, machine learning approaches and the detection and study of lateral gene transfers. TSP has co-authored 38 peer-reviewed papers - of which 8 are published in Nature and Science (6 as cover stories) and he is also co-author of the institute’s most cited paper for both 2010 and 2005.edit
The bacteria Yersinia pestis is the etiological agent of plague and has caused human pandemics with millions of deaths in historic times. How and when it originated remains contentious. Here, we report the oldest direct evidence of... more
The bacteria Yersinia pestis is the etiological agent of plague and has caused human pandemics with millions of deaths in historic times. How and when it originated remains contentious. Here, we report the oldest direct evidence of Yersinia pestis identified by ancient DNA in human teeth from Asia and Europe dating from 2,800 to 5,000 years ago. By sequencing the genomes, we find that these ancient plague strains are basal to all known Yersinia pestis. We find the origins of the Yersinia pestis lineage to be at least two times older than previous estimates. We also identify a temporal sequence of genetic changes that lead to increased virulence and the emergence of the bubonic plague. Our results show that plague infection was endemic in the human populations of Eurasia at least 3,000 years before any historical recordings of pandemics.
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We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no evidence of European admixture and... more
We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no evidence of European admixture and estimate contamination levels to be below 0.5%. We show that Aboriginal Australians are descendants of an early human dispersal into eastern Asia, possibly 62,000 to 75,000 years ago. This dispersal is separate from the one that gave rise to modern Asians 25,000 to 38,000 years ago. We also find evidence of gene flow between populations of the two dispersal waves prior to the divergence of Native Americans from modern Asian ancestors. Our findings support the hypothesis that present-day Aboriginal Australians descend from the earliest humans to occupy Australia, likely representing one of the oldest continuous populations outside Africa.
Research Interests: Human Evolution, Genomics, Phylogeography, Gene Flow, Population Genetics, and 28 moreScience, Native American, Multidisciplinary, The evolution of human diversity, Human evolutionary genetics, Phylogeny, Mitochondrial DNA, Humans, Far East, Computer Simulation, Haplotypes, Animals, Ancient DNA, out of Africa human dispersals, Asia, Male, Ethnic Groups, Mitochondrial Genome, Multiple Dispersals, Australian prehistory, Aboriginal origins, Western Australia, Human Genome, Linkage Disequilibrium, Hominidae, European Continental Ancestry Group, Asian Continental Ancestry Group, and Genome sequence
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Research Interests: Genetics, Hydrogen, Science, Oxidative Stress, Horizontal Gene Transfer, and 12 moreMultidisciplinary, Organelles, Humans, Animals, Trichomonas vaginalis, Genome sequence, Protozoan Proteins, Metabolic pathway, Gene Family, Sexually Transmitted Diseases, Lateral Gene Transfer, and Molecular Sequence Data
Research Interests: Bioinformatics, Genetics, Microbiology, Genomics, Obesity, and 18 moreComputational Biology, Health, Multidisciplinary, Nature, Spain, Gut Microbiota, Denmark, Overweight, Humans, Bacteria, Human health, Adult, Feces, Gastrointestinal Tract, Hola Amigos Y Gracias, Metagenome, Inflammatory Bowel Diseases, and Cohort Studies
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Research Interests: Molecular Evolution, Oxidative Stress, Horizontal Gene Transfer, Multidisciplinary, Nature, and 18 moreSignal Transduction, Virulence, Intestinal Parasites, Phylogeny, Genome evolution, Developing Country, Animals, Parasites, Trichomonas vaginalis, Genome Analysis, Glycolysis, Enzyme, Fermentation, Entamoeba histolytica, Metabolic pathway, Gene Family, Structure Function, and Lateral Gene Transfer
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Reports of plant-like and bacterial-like genes for a number of parasitic organisms, most notably those within the Apicomplexa and Kinetoplastida, have appeared in the literature over the last few years. Among the apicomplexan organisms,... more
Reports of plant-like and bacterial-like genes for a number of parasitic organisms, most notably those within the Apicomplexa and Kinetoplastida, have appeared in the literature over the last few years. Among the apicomplexan organisms, following discovery of the apicomplexan plastid (apicoplast), the discovery of plant-like genes was less surprising although the extent of transfer and the relationship of transferred genes to the apicoplast remained unclear. We used new genome sequence data to begin a systematic examination of the extent and origin of transferred genes in the Apicomplexa combined with a phylogenomic approach to detect potential gene transfers in four apicomplexan genomes. We have detected genes of algal nuclear, chloroplast (cyanobacterial) and proteobacterial origin. Plant-like genes were detected in species not currently harbouring a plastid (e.g. Cryptosporidium parvum) and putatively transferred genes were detected that appear to be unrelated to the function of the apicoplast. While the mechanism of acquisition for many of the identified genes is not certain, it appears that some were most likely acquired via intracellular gene transfer from an algal endosymbiont while others may have been acquired via horizontal gene transfer.
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Research Interests: Genetics, Microbiology, Medical Microbiology, Antibiotic Resistance, Virulence, and 17 moreDisease Outbreaks, Humans, Europe, Multidrug Resistance, Drug Resistance, Membrane transport, Plasmids, Membrane transport proteins, Gram-negative bacteria, Genome Comparison, Acinetobacter, Genome sequence, Acinetobacter baumannii, Species Specificity, Cross-infection, Acinetobacter Infections, and Molecular Sequence Data
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Genetic variants, including single-nucleotide polymorphisms (SNPs), are key determiners of interindividual differences in treatment efficacy and toxicity in childhood acute lymphoblastic leukemia (ALL). Although up to 13 chemotherapeutic... more
Genetic variants, including single-nucleotide polymorphisms (SNPs), are key determiners of interindividual differences in treatment efficacy and toxicity in childhood acute lymphoblastic leukemia (ALL). Although up to 13 chemotherapeutic agents are used in the treatment of this cancer, it remains a model disease for exploring the impact of genetic variation due to well-characterized cytogenetics, drug response pathways and precise monitoring of minimal residual disease. Here, we have selected clinically relevant genes and SNPs through literature screening, and on the basis of associations with key pathways, protein-protein interactions or downstream partners that have a role in drug disposition and treatment efficacy in childhood ALL. This allows exploration of pathways, where one of several genetic variants may lead to similar clinical phenotypes through related molecular mechanisms. We have designed a cost-effective, high-throughput capture assay of ∼25,000 clinically relevant SNPs, and demonstrated that multiple samples can be tagged and pooled before genome capture in targeted enrichment with a sufficient sequencing depth for genotyping. This multiplexed, targeted sequencing method allows exploration of the impact of pharmacogenetics on efficacy and toxicity in childhood ALL treatment, which will be of importance for personalized chemotherapy.
Research Interests: Genetics, Treatment Outcome, Leukemia, Adolescent, Molecular Mechanics, and 17 moreNext generation sequencing, Protein-Protein Interaction, Humans, Pharmacogenetics, Infant, Cost effectiveness, Phenotype, Clinical Sciences, Newborn Infant, Genotype, Single Nucleotide Polymorphism, Cost Benefit Analysis, Very high throughput, Genetic variation, MINIMAL RESIDUAL DISEASE, Acute Lymphoblastic Leukemia, and Child preschool
Post-translational modifications (PTMs) occur on almost all proteins analyzed to date. The function of a modified protein is often strongly affected by these modifications and therefore increased knowledge about the potential PTMs of a... more
Post-translational modifications (PTMs) occur on almost all proteins analyzed to date. The function of a modified protein is often strongly affected by these modifications and therefore increased knowledge about the potential PTMs of a target protein may increase our understanding of the molecular processes in which it takes part. High-throughput methods for the identification of PTMs are being developed, in particular within the fields of proteomics and mass spectrometry. However, these methods are still in their early stages, and it is indeed advantageous to cut down on the number of experimental steps by integrating computational approaches into the validation procedures. Many advanced methods for the prediction of PTMs exist and many are made publicly available. We describe our experiences with the development of prediction methods for phosphorylation and glycosylation sites and the development of PTM-specific databases. In addition, we discuss novel ideas for PTM visualization (exemplified by kinase landscapes) and improvements for prediction specificity (by using ESS – evolutionary stable sites). As an example, we present a new method for kinase-specific prediction of phosphorylation sites, NetPhosK, which extends our earlier and more general tool, NetPhos. The new server, NetPhosK, is made publicly available at the URL http://www.cbs.dtu.dk/services/NetPhosK/. The issues of underestimation, over-prediction and strategies for improving prediction specificity are also discussed.
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GRS is a graphic tool for retrieval and visualization of genome segments from partially or completely sequenced genomes. To facilitate visual identification of conserved genomic motifs, genes are color-coded according to their presumed... more
GRS is a graphic tool for retrieval and visualization of genome segments from partially or completely sequenced genomes. To facilitate visual identification of conserved genomic motifs, genes are color-coded according to their presumed functional roles. Aligned genes can be rapidly screened for potential homology by automatic retrieval and alignment of the corresponding protein sequences. Furthermore, the map location of any genome segment can be visually compared to the position of the same segment in other genomes or to the position of other segments within the same genome. The gene string analysis option of GRS allows the identification of genes that are identically arranged in any pairwise set of genomes. Finally, the program allows the user to create new gene table format files to enable comparisons of gene order structures in recently determined sequence data to the patterns of genes in already existing microbial and organellar databases. With the help of GRS, the genomic contexts of genes for which no identifiable homologues exist can be analyzed to provide an additional source of information for sequence annotations. We illustrate the use of GRS by analyzing the structure and distribution of phylogenetically conserved motifs in closely as well as more distantly related microbial genomes.
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Over the past few years it has become apparent that horizontal gene transfer (HGT) has played an important role in the evolution of pathogenic prokaryotes. What is less clear is the exact role that HGT has played in shaping the metabolism... more
Over the past few years it has become apparent that horizontal gene transfer (HGT) has played an important role in the evolution of pathogenic prokaryotes. What is less clear is the exact role that HGT has played in shaping the metabolism of eukaryotic organisms. The main problems are the reliable inference of HGT on a genomic scale as well as the functional assignment of genes in these poorly studied organisms. We have screened the completed genomes of the protists Entamoeba histolytica and Trichomonas vaginalis for cases of HGT from prokaryotes. Using a fast primary screen followed by a conservative phylogenetic approach, we found 68 and 153 recent cases of HGT in the respective organisms. The majority of transferred genes that fall into functional categories code for enzymes involved in metabolism. We found a broad range of prokaryotic lineages represented among the donors, but organisms that share similar environmental niches with E. histolytica and T. vaginalis, such as the gut and the vaginal mucosa, dominate.
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Research Interests: Chemical Engineering, Algorithms, Artificial Intelligence, Analytical Chemistry, Mass Spectrometry, and 30 moreBiological Sciences, Saccharomyces cerevisiae, Cercopithecus aethiops, Humans, Computer Simulation, Mice, Animals, Analytical, Trypsin, Phosphorylation, Proteins, Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis, Immunoprecipitation, Online Systems, High Pressure Liquid Chromatography, CHEMICAL SCIENCES, Molecular cloning, Reproducibility of Results, Protozoan Proteins, Amino Acid Sequence, Sensitivity and Specificity, Acanthamoeba, Polyacrylamide Gel Electrophoresis, Cell Cycle Proteins, Recombinant Proteins, Proteome, DNA binding proteins, Artificial Neural Network, Phosphopeptides, and Molecular Sequence Data
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Research Interests: Technology, Obesity, Microbial Ecology, Symbiosis, Ecophysiology, and 14 moreMetagenomics, Environmental Biotechnology, Biological Sciences, Environmental Sciences, Humans, Ecosystems, Bacteria, Microorganisms, Feces, Gastrointestinal Tract, Metabolome, Metagenome, Inflammatory Bowel Diseases, and Pharmaceutical preparations
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The global feature of the completely sequenced Alcanivorax borkumensis SK2 type strain chromosome is its symmetry and homogeneity. The origin and terminus of replication are located opposite to each other in the chromosome and are... more
The global feature of the completely sequenced Alcanivorax borkumensis SK2 type strain chromosome is its symmetry and homogeneity. The origin and terminus of replication are located opposite to each other in the chromosome and are discerned with high signal to noise ratios by maximal oligonucleotide usage biases on the leading and lagging strand. Genomic DNA structure is rather uniform throughout the chromosome with respect to intrinsic curvature, position preference or base stacking energy. The orthologs and paralogs of A. borkumensis genes with the highest sequence homology were found in most cases among γ-Proteobacteria, with Acinetobacter and P. aeruginosa as closest relatives. A. borkumensis shares a similar oligonucleotide usage and promoter structure with the Pseudomonadales. A comparatively low number of only 18 genome islands with atypical oligonucleotide usage was detected in the A. borkumensis chromosome. The gene clusters that confer the assimilation of aliphatic hydrocarbons, are localized in two genome islands which were probably acquired from an ancestor of the Yersinia lineage, whereas the alk genes of Pseudomonas putida still exhibit the typical Alcanivorax oligonucleotide signature indicating a complex evolution of this major hydrocarbonoclastic trait.
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The Bacteroides fragilis NCTC 9343 genome is the fifth member of the Bacteroidetes/Chlorobi group to be sequenced and the second Bacteroides fragilis strain. The Bacteroides fragilis NCTC 9343 genome shows considerable variation even... more
The Bacteroides fragilis NCTC 9343 genome is the fifth member of the Bacteroidetes/Chlorobi group to be sequenced and the second Bacteroides fragilis strain. The Bacteroides fragilis NCTC 9343 genome shows considerable variation even within the same strain and 'invertable promoters' appear to regulate much of this variance in many surface-exposed and secreted proteins (Cerdeno-Tárraga et al., 2005). Characteristics of the genome are given in Table 1.
Abstract We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the∼ 160-megabase genome, reflecting a recent massive... more
Abstract We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the∼ 160-megabase genome, reflecting a recent massive expansion of genetic material.
Abstract To study the origin and evolution of biochemical pathways in microorganisms, we have developed methods and software for automatic, large-scale reconstructions of phylogenetic relationships. We define the complete set of... more
Abstract To study the origin and evolution of biochemical pathways in microorganisms, we have developed methods and software for automatic, large-scale reconstructions of phylogenetic relationships. We define the complete set of phylogenetic trees derived from the proteome of an organism as the phylome and introduce the term phylogenetic connection as a concept that describes the relative relationships between taxa in a tree.
Abstract GenePublisher, a system for automatic analysis of data from DNA microarray experiments, has been implemented with a web interface at http://www. cbs. dtu. dk/services/GenePublisher. Raw data are uploaded to the server together... more
Abstract GenePublisher, a system for automatic analysis of data from DNA microarray experiments, has been implemented with a web interface at http://www. cbs. dtu. dk/services/GenePublisher. Raw data are uploaded to the server together with a specification of the data. The server performs normalization, statistical analysis and visualization of the data. The results are run against databases of signal transduction pathways, metabolic pathways and promoter sequences in order to extract more information.
Abstract The intestinal parasite Entamoeba histolytica is one of the first protists for which a draft genome sequence has been published. Although the genome is still incomplete, it is unlikely that many genes are missing from the list of... more
Abstract The intestinal parasite Entamoeba histolytica is one of the first protists for which a draft genome sequence has been published. Although the genome is still incomplete, it is unlikely that many genes are missing from the list of those already identified. In this chapter we summarise the features of the genome as they are currently understood and provide previously unpublished analyses of many of the genes.
ABSTRACT Accurate strain identification is essential for anyone working with bacteria. For many species, multilocus sequence typing (MLST) is considered the “gold standard” of typing, but it is traditionally performed in an expensive and... more
ABSTRACT Accurate strain identification is essential for anyone working with bacteria. For many species, multilocus sequence typing (MLST) is considered the “gold standard” of typing, but it is traditionally performed in an expensive and time-consuming manner. As the costs of whole-genome sequencing (WGS) continue to decline, it becomes increasingly available to scientists and routine diagnostic laboratories. Currently, the cost is below that of traditional MLST.
Background Trichomonas vaginalis is the most common non-viral human sexually transmitted pathogen and importantly, contributes to facilitating the spread of HIV. Yet very little is known about its surface and secreted proteins mediating... more
Background Trichomonas vaginalis is the most common non-viral human sexually transmitted pathogen and importantly, contributes to facilitating the spread of HIV. Yet very little is known about its surface and secreted proteins mediating interactions with, and permitting the invasion and colonisation of, the host mucosa. Initial annotations of T. vaginalis genome identified a plethora of candidate extracellular proteins. Results Data mining of the T.
Background Post-translational phosphorylation is one of the most common protein modifications. Phosphoserine, threonine and tyrosine residues play critical roles in the regulation of many cellular processes. The fast growing number of... more
Background Post-translational phosphorylation is one of the most common protein modifications. Phosphoserine, threonine and tyrosine residues play critical roles in the regulation of many cellular processes. The fast growing number of research reports on protein phosphorylation points to a general need for an accurate database dedicated to phosphorylation to provide easily retrievable information on phosphoproteins.
Background For most sequenced prokaryotic genomes, about a third of the protein coding genes annotated are" orphan proteins", that is, they lack homology to known proteins. These hypothetical genes are typically short and randomly... more
Background For most sequenced prokaryotic genomes, about a third of the protein coding genes annotated are" orphan proteins", that is, they lack homology to known proteins. These hypothetical genes are typically short and randomly scattered throughout the genome. This trend is seen for most of the bacterial and archaeal genomes published to date. Results In contrast we have found that a large fraction of the genes coding for such orphan proteins in the Methanopyrus kandleri AV19 genome occur within two large regions.
Genomes of the month Twelve new microbial genomes have been published since the last 'Genome Update'column was written. The collection of this month's genomes, listed in Table 1, include five published bacterial genomes ('Candidatus... more
Genomes of the month Twelve new microbial genomes have been published since the last 'Genome Update'column was written. The collection of this month's genomes, listed in Table 1, include five published bacterial genomes ('Candidatus Blochmannia pennsylvanicus', Colwellia psychrerythraea, Mycoplasma hyopneumoniae, Mycoplasma synoviae and Pseudomonas syringae pv. syringae B728a).
ABSTRACT The whole-genome sequence of an epidemic, multidrug-resistant Acinetobacter baumannii strain (strain ACICU) belonging to the European clone II group and carrying the plasmid-mediated bla OXA-58 carbapenem resistance gene was... more
ABSTRACT The whole-genome sequence of an epidemic, multidrug-resistant Acinetobacter baumannii strain (strain ACICU) belonging to the European clone II group and carrying the plasmid-mediated bla OXA-58 carbapenem resistance gene was determined. The A. baumannii ACICU genome was compared with the genomes of A. baumannii ATCC 17978 and Acinetobacter baylyi ADP1, with the aim of identifying novel genes related to virulence and drug resistance. A.
Summary: InterMap3D predicts co-evolving protein residues and plots them on the 3D protein structure. Starting with a single protein sequence, InterMap3D automatically finds a set of homologous sequences, generates an alignment and... more
Summary: InterMap3D predicts co-evolving protein residues and plots them on the 3D protein structure. Starting with a single protein sequence, InterMap3D automatically finds a set of homologous sequences, generates an alignment and fetches the most similar 3D structure from the Protein Data Bank (PDB). It can also accept a user-generated alignment.
Genomes of the month Ten new microbial genomes were published since the last 'Genome Update'column was written. The collection of this month's prokaryotic genomes, listed in Table 1, consists of one archaeon (Sulfolobus acidocaldarius)... more
Genomes of the month Ten new microbial genomes were published since the last 'Genome Update'column was written. The collection of this month's prokaryotic genomes, listed in Table 1, consists of one archaeon (Sulfolobus acidocaldarius) and five bacteria (Corynebacterium jeikeium, Haemophilus influenzae, Pseudomonas fluorescens, Rickettsia felis and Xanthomonas campestris).
Abstract We describe here the complete genome sequence (1,111,523 base pairs) of the obligate intracellular parasite Rickettsia prowazekii, the causative agent of epidemic typhus. This genome contains 834 protein-coding genes. The... more
Abstract We describe here the complete genome sequence (1,111,523 base pairs) of the obligate intracellular parasite Rickettsia prowazekii, the causative agent of epidemic typhus. This genome contains 834 protein-coding genes. The functional profiles of these genes show similarities to those of mitochondrial genes: no genes required for anaerobic glycolysis are found in either R.
Abstract We report here the genome sequence of an ancient human. Obtained from~ 4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average... more
Abstract We report here the genome sequence of an ancient human. Obtained from~ 4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20×, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously.