Snel Lab >>

Evolutionary Genomics and Integrative Bioinformatics

Research agenda

Snel group picture

Currently molecular biology is generating information on the molecular properties of cells and organisms at an incredible pace. For example we know the complete genome sequence of a large number of species and the number of these genome sequences is increasing. Not only do these so called high-throughput experiments generate complete pictures of the genetic information of cells, but other techniques measure the level of expression of all genes at the same time, or measure all the interactions between all the proteins present in a cell. Bioinformatics is obviously needed for the storage and primary analysis of these huge volumes of biomolecular data. More interestingly, these data uniquely allow bioinformatics to make biological discoveries that hitherto were not possible.

We here use these genome scale data to perform research in evolutionary genomics: i.e. what rules govern the presence and absence of genes across genomes, how do protein complexes evolve, how does the protein interaction network evolve, how do signal transduction pathways evolve, what is the role of gene duplication in the evolution of protein complexes and the interaction network. These research questions are carried out using bionformatics to compare genome sequences and integrate highthrougput data sets such as yeast-2-hybrid data or micro-array expression data. All research efforts rely heavily on advanced sequence analysis and orthology detection. At the same time our insights from genome evolution and the analysis of high-throughput data allow the development of tools to predict the cellular function of experimentally poorly characterized genes.

The Evolutionary Genomics and Integrative Bioinformatics Group is part of Theoreotical Biology and Bioinformatics.

Members

Former Members / Students

  • Jos Boekhorst, Postdoc
  • Sandra Botelho, PhD student
  • Nijuscha Gruhn, PhD Student (visiting, AG Heyl, FU Berlin)
  • John Van Dam, PhD student
  • Richard Foppen, Master student
  • Erik Hoogendoorn, Master student
  • Brand Recter, Master student
  • Harmen Van Rossum, Master student
  • Floor Venema, Master student
  • Rui Peng Wang, Master student (VU)
  • Laura Hamerslag, Bachelors Student

Open Positions

PhD postion in a NWO TOP-GO project entitled "Evolutionary systems biology and molecular networks linking nutrient status to growth."
Snel Lab, Theoretical Biology and Bioinformatics, Utrecht University

Research projects for Master students (6-12 months)

  • Amino acid adaptation of extremophiles (Gabino Sanchez-Perez)
  • Evolution of phosphorylation based regulatory networks (Jos Boekhorst & Berend Snel)
  • RasGAPs and the evolution of Ras signaling pathways (John van Dam) (DOC)
  • Fate of duplicated genes in fungi and animals (Like Fokkens & Berend Snel)
  • Fate of duplicated genes in plants with regards to their spatio-temporal expression and epigenetic status (Gabino Sanchez-Perez)
  • Gene fusion and fission in the genomes of Eukaryotes (Like Fokkens & Berend Snel) (DOC)
  • Phosphoproteomics in the plant pathogen Phytophthora infestans (Michael Seidl) (pdf)

Publications

2012

Stassen JH, Seidl MF, Vergeer PW, Nijman IJ, Snel B, Cuppen E, van den Ackerveken G.(2012) Effector identification in the lettuce downy mildew Bremia lactucae by massively parallel transcriptome sequencing. Mol Plant Pathol. (1. Feb 2012) [Epub ahead of print]

Seidl MF, Van den Ackerveken G, Govers F, Snel B (2012) Reconstruction of oomycete genome evolution identifies differences in evolutionary trajectories leading to present-day large gene families. Genome Biol Evol. (Jan 13. 2012) [Epub ahead of print]

Database independent proteomics analysis of the ostrich and human proteome. Altelaar AF, Navarro D, Boekhorst J, van Breukelen B, Snel B, Mohammed S, Heck AJ. (2012) Proc Natl Acad Sci U S A. (2012) 109:407-412

Mithoe SC, Boersema PJ, Berke L, Snel B, Heck AJ, Menke FL. (2012) Targeted quantitative phosphoproteomics approach for the detection of phospho-tyrosine signaling in plants. J Proteome Res. (2012) 11:438-448

2011

Schluepmann H, Berke L,Sanchez-Perez GF (2011) Metabolism control over growth: a case for trehalose-6-phosphate in plants. J. Exp. Bot. (2011)

Prasad K, Grigg SP, Barkoulas M, Yadav RK, Sanchez-Perez GF, Pinon V, Blilou I, Hofhuis H, Dhonukshe P, Galinha C, Mähönen AP, Muller WH, Raman S, Verkleij AJ, Snel B, Reddy GV, Tsiantis M, Scheres B (2011) Arabidopsis PLETHORA Transcription Factors Control Phyllotaxis. Curr Biol (2011)

Cabral A, Stassen JHM, Seidl MF, Bautor J, Parker JE, et al. (2011) Identification of Hyaloperonospora arabidopsidis Transcript Sequences Expressed during Infection Reveals Isolate-Specific Effectors. PLoS ONE (2011) 6(5): e19328.

Ten Hove CA,De Jong M , Lapin D, Andel A, Sanchez-Perez GF, Tarutani Y, Suzuki Y, Heidstra R, Van den Ackerveken G (2011) Trans-Repression of Gene Activity Upstream of T-DNA Tagged RLK902 Links Arabidopsis Root Growth Inhibition and Downy Mildew Resistance. PLoS One (2011) 6(4): e19028

Ten Hove CA, Bochdanovits Z , Jansweijer VMA, Koning FG, Berke L, Sanchez-Perez GF, Scheres B, Heidstra R (2011) Probing the roles of LRR RLK genes in Arabidopsis thaliana roots using a custom T-DNA insertion set. Plant Molecular Biology (2011) May;76(1-2):69-83

Van Dam TJP, Bos JL, Snel B (2011) Evolution of the Ras-like small GTPases and their regulators. Small GTPases (2011) 2:1, 1-13

Ding VM, Boersema PJ, Foong LY, Preisinger C, Koh G, Natarajan S, Lee DY, Boekhorst J, Snel B, Lemeer S, Heck AJ, Choo A. (2011) Tyrosine phosphorylation profiling in fgf-2 stimulated human embryonic stem cells. PLoS One (2011) Mar;6(3):e17538

Seidl MF, Van Den Ackerveken G, Govers F, Snel B (2011) A domain-centric analysis of oomycete plant pathogen genomes reveals unique protein organization. Plant Physiology 155:628-644 (2011), (Published Online 30.11.2010)

2010

Van Wageningen S, Kemmeren, Lijnzaad P, Margaritis T, Benschop JJ , de Castro IJ, Van Leenen D, Groot Koerkamp MJA, Ko CW, Miles AJ, Brabers N, Brok MO, Lenstra TL, Fiedler D , Fokkens L, Aldecoa R, Apweiler E, Taliadouros V, Sameith K, Van de Pasch LAL, Van Hooff SR, Bakker LV,.Krogan NJ, Snel B, Holstege FCP (2010) Functional Overlap and Regulatory Links Shape Genetic Interactionsbetween Signaling Pathways. Cell 143(6):991-1004,

Calis JJA, Sanchez-Perez GF, Kesmir C (2010) MHC class I molecules exploit the low G+C content of pathogen genomes for enhanced presentation. Eur J Immunol 2010 Jul, 40(10):2699-2709

Booijink CC, Boekhorst J, Zoetendal EG, Smidt H, Kleerebezem M, de Vos WM (2010) Metatranscriptome analysis of the human fecal microbiota reveals subject-specific expression profiles, with genes encoding proteins involved in carbohydrate metabolism being dominantly expressed Appl Environ Microbiol 2010 Aug, 76(16):5533-40. Epub 2010 Jun 18 PMID: 2056228

van Schaik W, Top J, Riley DR, Boekhorst J, Vrijenhoek JE, Schapendonk CM, Hendrickx AP, Nijman IJ, Bonten MJ, Tettelin H, Willems RJ (2010) Pyrosequencing-based comparative genome analysis of the nosocomial pathogen Enterococcus faecium and identification of a large transferable pathogenicity islandBMC Genomics 2010 Apr 14, 11:239 PMID: 20398277

Bennett T, van den Toorn A, Sanchez-Perez GF, Campilho A, Willemsen V, Snel B, Scheres B (2010) SOMBRERO, BEARSKIN1, and BEARSKIN2 Regulate Root Cap Maturation in Arabidopsis Plant Cell 2010, 22:640-654, PMID: 20197506

Fokkens L, Botelho SMC, Boekhorst J, Snel B (2010) Enrichment of homologs in insignificant BLAST hits by co-complex network alignment BMC Bioinformatics 2010, 11:86 doi:10.1186/1471-2105-11-86 PMID: 20152020

2009

Kamikawa R, Sanchez-Perez GF, Sako Y, Roger AJ, Inagaki Y. (2009) Expanded phylogenies of canonical and non-canonical types of methionine adenosyltransferase reveal a complex history of these gene families in eukaryotes. Mol Phylogenet Evol 2009, 53(2):565-570

Boersema PJ, Foong LY, Ding VM, Lemeer S, van Breukelen B, Philp R, Boekhorst J, Snel B, den Hertog J, Choo AB and Heck AJ.(2009) In depth qualitative and quantitative profiling of tyrosine phosphorylation using a combination of phosphopeptide immuno-affinity purification and stable isotope dimethyl labeling.Mol Cell Proteomics. 9:84-99 PMID: 19770167

Seidl MF, Schultz J (2009) Evolutionary flexibility of protein complexes. BMC Evolutionary Biology 2009, 9:155. doi:10.1186/1471-2148-9-155

van Dam TJP, Rehmann H, Bos JL, Snel B (2009) Phylogeny of the CDC25 homology domain reveals rapid differentiation of Ras pathways between early animals and fungi. Cell Signal. 2009 Jun 27. doi:10.1016/j.cellsig.2009.06.004

Fokkens L and Snel B(2009) Cohesive versus flexible evolution of functional modules in eukaryotes.Fokkens L, Snel B.PLoS Comput Biol. 5, e1000276 PMID: 19180181

2008

Szklarczyk R, Huynen MA and Snel B.(2008) Complex fate of paralogs.BMC Evol Biol. 8, 337 PMID: 19094234

Boekhorst J, van Breukelen B, Heck AJ, Snel B.Comparative phosphoproteomics reveals evolutionary and functional conservation of phosphorylation across eukaryotes.Genome Biol. 2008 9, R144.PMID: 18828897

van Dam TJP and Snel B(2008) Protein complex evolution does not involve extensive network rewiring.PLoS Comput Biol.4, e1000132.

Dutilh BE, Snel B, Ettema TJ and Huynen MA (2008) Signature Genes as a Phylogenomic Tool.Mol Biol Evol. 25, 1659-1667

Cordero OX, Snel B and Hogeweg P (2008) Coevolution of gene families in prokaryotes.Genome Res. 18, 462-468

2007

Boekhorst J and Snel B (2007) Identification of homologs in insignificant blast hits by exploiting extrinsic gene properties.BMC Bioinformatics 8, 356

van Noort V*, Snel B* and Huynen MA (2007) Exploration of the omics evidence landscape: adding qualitative labels to predicted protein-protein interactions.Genome Biol. 8, R197 *Contributed equally

van der Heijden RT, Snel B, van Noort V and Huynen MA(2007) Orthology prediction at Scalable Resolution by Phylogenetic Tree analysis.BMC Bioinformatics 8, 83

Dutilh BE, van Noort V, van der Heijden RT, Boekhout T, Snel B and Huynen MA. (2007)Assessment of phylogenomic and orthology approaches for phylogenetic inference.Bioinformatics 23, 815-824

von Mering C, Jensen LJ, Kuhn M, Chaffron S, Doerks T, Kruger B, Snel B. and Bork P.(2007) STRING 7--recent developments in the integration and prediction of protein interactions.Nucleic Acids Res.35, D358-D362

2006

Kuramae EE, Robert V, Snel B, Weiss M and Boekhout T(2006) Phylogenomics reveal a robust fungal tree of life.FEMS Yeast Res. 6,1213-1220

Kuramae EE, Robert V, Snel B and Boekhout T(2006) Conflicting phylogenetic position of Schizosaccharomyces pombe.Genomics 88, 387-393

Oti M, Snel B, Huynen MA and Brunner HG(2006) Predicting disease genes using protein-protein interactions.J. Med. Genet.43, 691-698

Strous M, Pelletier E, Mangenot S, Rattei T, Lehner A, Taylor MW, Horn H, Daims H, Bartol-Mavel D, Wincker P, Barbe V, Fonknechten N, Vallenet D, Segurens B, Schenowitz-Truong C, Médigue C, Collingro A, Snel B., Dutilh BE, op den Camp HJM., van der Drift C, Cirpus I, van de Pas-Schoonen KT, Harhangi HR, van Niftrik L, Schmid M, Keltjens J, van de Vossenberg J, Kartal B, Meier H, Frishman D, Huynen MA., Mewes HW, Weissenbach J, Jetten MSM, Wagner M , Le Paslier D(2006) Deciphering the evolution and metabolism of an anammox bacterium from a community genome.Nature, 440, 790-794

Gabaldon T, Snel B, van Zimmeren F, Hemrika W, Tabak H, Huynen MA (2006) Origin and evolution of the peroxisomal proteome.Biol. Direct, 1,8

Ciccarelli FD, Doerks T, von Mering C, Creevey CJ, Snel B,Bork P(2006) Toward automatic reconstruction of a highly resolved tree of life.Science,311,1283-1287

Dutilh BE, Huynen MA, Snel B (2006) A global definition of expression context is conserved between orthologs, but does not correlate with sequence conservation.BMC Genomics,7,10

2005

Notebaart RA, Huynen MA, Teusink B, Siezen RJ, Snel B (2005) Correlation between sequence conservation and the genomic context after gene duplication.Nucleic Acids Res., 33,6164-6171

Snel B, Huynen MA, Dutilh BE (2005) Genome trees and the nature of genome evolution.Annu Rev Microbiol.,59,191-209

Huynen MA, Gabaldon T, Snel B (2005) Variation and evolution of biomolecular systems: searching for functional relevance. FEBS Lett., 579,1839-1845

Huynen MA, Spronk CA, Gabaldon T, Snel B (2005) Combining data from genomes, Y2H and 3D structure indicates thatBolA is a reductase interacting with a glutaredoxin. FEBS Lett., 579, 591-596

von Mering C, Jensen LJ, Snel B, Hooper SD, Krupp M, Foglierini M, Jouffre N, Huynen MA, Bork P (2005) STRING: known and predicted protein-protein associations, integrated and transferred across organisms.Nucleic Acids Res., 33 Database Issue:D433-437

2004

Snel B, van Noort V and Huynen MA (2004) Gene co-regulation is highly conserved in the evolution of eukaryotes and prokaryotes.Nucleic Acids. Res., 32, 4725-4731

Huynen MA, Snel B, van Noort V (2004) Comparative genomics for reliable protein-function prediction from genomic data.Trends Genet., 20, 340-344

Dutilh BE, Huynen MA, Bruno WJ, Snel B (2004) The Consistent Phylogenetic Signal in Genome Trees Revealed by Reducing the Impact of Noise.J. Mol. Evol., 58, 527-539

Snel B. Huynen MA (2004) Quantifying modularity in the evolution of biomolecular systems.Genome Res., 14, 391-397

van Noort V, Snel B, Huynen MA (2004) The yeast coexpression network has a small-world, scale-free architecture and can be explained by a simple model.EMBO Rep., 5, 280-284

2003

Morett E, Korbel JO, Rajan E, Saab-Rincon G, Olvera L, Olvera M, Schmidt S, Snel B, Bork P (2003) Systematic discovery of analogous enzymes in thiamin biosynthesis.Nat. Biotechnol. , 21 790-795

van Noort V, Snel B, Huynen MA (2003) Predicting gene function by conserved co-expression.Trends Genet., 19, 238-242

Huynen MA, Snel B, von Mering C, Bork P (2003) Function prediction and protein networks.Curr. Opin. Cell. Biol., 15, 191-198

von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B (2003) STRING: a database of predicted functional associations between proteins.Nucleic Acids. Res., 31, 258-261

Huynen MA, Snel B (2003) Exploiting the variations in the genomic associations of genes to predict pathways and reconstruct their evolution.In: Frontiers in Computational Genomics 145-166 (Editors, Galperin, M. Y. & Koonin, E. V.) Caister Academic Press

2002

Dandekar T, Snel B, Schmidt S, Lathe W, Suyama M, Huynen MA. Bork P (2002) Comparative Genome Analysis of the Mollicutes.In: Molecular Biology and Pathogenity of Mycoplasmas255-278 (Editors, Razin S, Herrmann R) Kluwer Academic / Plenum Publishers,

Schell MA, Karmirantzou M, Snel B, Vilanova D, Berger B, Pessi G, Zwahlen MC, Desiere F, Bork P, Delley M, Pridmore RD, Arigoni F (2002) The genome sequence of Bifidobacterium longum reflects its adaptation to the human gastrointestinal tract. Proc. Natl. Acad. Sci. USA, 22, 14422-14427

Snel B (2002) Comparative Genome Analysis and Genome Evolution Ph. D. Thesis Utrecht University

Snel B, Bork P, Huynen MA (2002) Conservation of gene co-regulation in prokaryotes and eukaryotes. Trends Biotechnol., 20, 410

von Mering C, Krause R, Snel B, Cornell M, Oliver SG, Fields S, Bork P (2002) Comparative assessment of large-scale data sets of protein-protein interactions. Nature, 417, 399-403

Snel B, Bork P, Huynen MA (2002) The identification of functional modules from the genomic association of genes. Proc. Natl. Acad. Sci. USA, 99, 5890-5895

Korbel JO+, Snel B+, Huynen MA, Bork P (2002).SHOT: a web server for the construction of genome phylogenies. Trends Genet., 18, 158-162
+ These authors contributed equally.

Snel B, Bork P, Huynen, MA (2002) Genomes in Flux: The Evolution of Archaeal and Proteobacterial Gene Content Genome Res., 12, 17-25

2001

Huynen MA, Snel B, Bork P, Gibson TJ (2001) The phylogenetic distribution of frataxin indicates a role in iron-sulfur cluster protein assembly. Hum. Mol. Genet., 10, 2463-2468

Huynen MA, Snel B, Bork P (2001) Inversions and the dynamics of eukaryotic gene order. Trends Genet., 17, 304-306

2000

Lathe III WC, Snel B,Bork P (2000) Gene context conservation of a higher order than operons. Trends Biochem. Sci., 25, 469-474

Bork P, Snel B, Lehmann G, Suyama M, Dandekar T, Lathe III W, Huynen MA (2000) Comparative genome analysis: exploiting the context of genes to infer evolution and predict function. In: Comparative Genomics, emprical and analytical approaches to gene order dynamics, map alignment and the evolution of gene families, Computational biology series volume 1. 281-294 (Editors: Sankoff, D., & Nadeau, J. H.) Kluwer academic publishers

Snel B, Lehmann G, Bork P, Huynen MA (2000) STRING: A web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. Nucleic Acids Res., 28, 3442-3444
This web-server is available at http://www.Bork.EMBL-Heidelberg.de/STRING/

Dandekar T, Huynen M, Regula JT, Ueberle B, Zimmermann CU, Andrade MA, Doerks T, Sanchez-Pulido L, Snel B, Suyama M, Yuan YP, Herrmann R, Bork, P (2000) Re-annotating the Mycoplasma pneumoniae genome sequence: adding value, function and reading frames. Nucleic Acids Res., 28, 3278-3288

Huynen MA, Snel B, Lathe III W, Bork P (2000) Predicting protein function by genomic context: quantative evaluation and qualitativeinferences Genome Res., 10, 1204-1210

Huynen MA, Snel B, Lathe III W, Bork P (2000) Exploitation of gene context. Curr. Opin. Struct. Biol., 10, 366-370

Huynen MA, Snel B (2000) Gene and context: integrative approaches to genome analysis. Adv. Prot. Chem., 54, 345-380

Snel B, Bork P, Huynen MA (2000) Genome evolution: gene fusion versus gene fission. Trends Genet., 16, 9-11

1999

Huynen MA, Snel B, Bork P (1999) Lateral Gene Transfer, Genome Surveys, and the Phylogeny of Prokaryotes Science, 286, 1443a (in Technical Comments)

Dandekar T, Schuster S, Snel B, Huynen MA, Bork P (1999) Pathway alignment: application to the comparative analysis of glycolytic enzymes. Biochem J., 343, 115-124

Bork P, Doerks T, Springer TA ,Snel B. (1999) Domains in plexins: links to integrins and transcription factors. Trends Biochem. Sci., 24, 261-263

Bork P, Dandekar T, Snel B, Huynen MA (1999) Genome Comparsions to Monitor Molecular Evolution. In: MicrobialEvolution and Infection. 80-92 (Goebel, U.B., Ruf, B.R.) Einhorn-Presse Verlag Reinbek

Snel B, Bork P, Huynen MA (1999) Genome phylogeny based on gene content. Nature Genet., 21,108-110

1998

Dandekar T, Snel B, Huynen MA, Bork P (1998) Conservation of gene order: a fingerprint of proteins that physicallyinteract. Trends Biochem. Sci., 23, 324-328