Jurgen Nijkamp
Jurgen Nijkamp
- T
- +31 15 27 85859
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- J.F.Nijkamp@tudelft.nl
Faculty of Electrical Engineering, Mathematics and Computer Science
Intelligent Systems
Mekelweg 4
2628 CD Delft
The Netherlands
Office: HB 11.250
Intelligent Systems
Mekelweg 4
2628 CD Delft
The Netherlands
Office: HB 11.250
Research
In the Kluyver Centre, several evolutionary engineering projects have been
formulated. The goal is to enhance strains by selecting for a desired
phenotype, i.e. a certain protein expression or metabolic flux. It is now
feasible to reverse-engineer the resulting strains by sequencing their
genomes and looking for mutations with respect to the sequence of the
reference strain. However, discovering which of the mutations found is (are)
responsible for the phenotypic change is still a challenge. In this project, we
intend to develop bioinformatics tools to find, rank and interpret the
mutations found. To this end, we will construct a novel mutation-phenotype
assocation model. Ultimately, inverting this model should allow us to find
promising genomic targets for engineering a desired phenotype.
Teaching
I am assistant in the computer labs of the following courses:
- IN4085 Pattern Recognition (2012-2013 Q1 & Q2)
- IN4085 Pattern Recognition (2010-2011 Q1 & Q2)
- LB2591 Genome-scale data analysis (2009 Q1)
Research Highlights
Laboratory evolution yields novel lactate transporters and aneuploidy
Laboratory evolution is a powerful approach in applied and fundamental yeast research, but complete elucidation of the molecular basis of evolved phenotypes remains a challenge. In this study, DNA microarray-based transcriptome analysis and whole-genome resequencing were used to investigate evolution of novel lactate transporters in Saccharomyces cerevisiae that can replace Jen1p, the only documented S. cerevisiae lactate transporter. To this end, a jen1Δ mutant was evolved for growth on lactate in serial batch cultures. Single-nucleotide changes were found in the acetate transporter gene ADY2, which were confirmed to mutate ADY2 into an efficient lactate transporter. Due to the strong selective advantage of having more copies of this novel lactate transporter, its gene became triplicated by formation of a novel isochromome III, carrying two additional ADY2 copies.Related publications
People involved
Jurgen Nijkamp, Dick de RidderThe genome sequence of a yeast for modern industrial biotechnology
Saccharomyces cerevisiae CEN.PK 113-7D is widely used for metabolic engineering and systems biology research in industry and academia. We sequenced, assembled, annotated and analyzed its genome. Single-nucleotide variations (SNV), insertions/deletions (indels) and differences in genome organization compared to the reference strain S. cerevisiae S288C were analyzed. In addition to a few large deletions and duplications, nearly 3000 indels were identified in the CEN.PK113-7D genome relative to S288C. These differences were overrepresented in genes whose functions are related to transcriptional regulation and chromatin remodelling. Some of these variations were caused by unstable tandem repeats, suggesting an innate evolvability of the corresponding genes. Besides a previously characterized mutation in adenylate cyclase, the CEN.PK113-7D genome sequence revealed a significant enrichment of non-synonymous mutations in genes encoding for components of the cAMP signalling pathway. Some phenotypic characteristics of the CEN.PK113-7D strains were explained by the presence of additional specific metabolic genes relative to S288C. In particular, the presence of the BIO1 and BIO6 genes correlated with a biotin prototrophy of CEN.PK113-7D. Furthermore, the copy number, chromosomal location and sequences of the MAL loci were resolved. The assembled sequence reveals that CEN.PK113-7D has a mosaic genome that combines characteristics of laboratory strains and wild-industrial strains.Related publications
- De novo sequencing, assembly and analysis of the genome of the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D, a model for modern industrial biotechnology
- Integrating genome assemblies with MAIA
People involved
Jurgen Nijkamp, Dick de Ridder, Marcel van den Broek, Marcel ReindersPredicting protein secretion success
The cell-factory Aspergillus niger is widely used for industrial enzyme production. Selecting enzymes for large-scale production requires costly lab work to test for successful high-level secretion of the over-expressed enzyme. To reduce the amount of lab work, we developed a sequence-based classifier that predicts successful high-level secretion of homologous proteins. This enables the selection of a subset of potential enzymes out of a large set of enzymes.
A dataset of 638 proteins was used to train and validate a classifier, using a 10-fold cross-validation protocol. Using a linear discriminant classifier, an average accuracy of 0.85 was achieved, which in practice could lead to half the amount of lab work.
Feature selection results indicate what features are mostly defining for successful protein production,
which could be an interesting lead to couple sequence characteristics to biological processes involved in protein production and secretion.Related publications
People involved
Bastiaan v.d. Berg, Jurgen Nijkamp, Marcel Reinders, Dick de RidderMAIA: Integrating genome assemblies
De novo assembly of a eukaryotic genome with next-generation sequencing data is still a challenging task. Over the past few years several assemblers have been developed, often suitable for one specific type of sequencing data. The number of known genomes is expanding rapidly, therefore it becomes possible to use multiple reference genomes for assembly projects. We introduce an assembly integrator that makes use of all available data, i.e. multiple de novo assemblies and mappings against multiple related genomes, by optimizing a weighted combination of criteria.
The developed algorithm was applied on the de novo sequencing of the Saccharomyces cerevisiae CEN.PK 113-7D strain. Using Solexa and 454 read data, two de novo and three comparative assemblies were constructed and subsequently integrated, yielding 29 contigs, covering more than 12 Mbp; a drastic improvement compared with the single assemblies.