From Computational Biology Group
We just published a new method for discovering new pioneer transcription factors, i.e., transcription factors that play an important role in the establishment and maintenance of open chromatin. The method basically associates transcription factor expression with chromatin accessibility genome-wide in multiple cell lines. Applied to the ENCODE data, it rediscovers known pioneer transcription factors along with new ones. It shows yet again that novel biological insights can be obtained by sophisticated analysis of large-scale public data sets. The paper is published in Plos Computational Biology .
Using gene expression data and other genomic information we constructed 394 cell type and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity between transcription factors, enhancers, promoters and genes. Each of these networks describes hundreds of thousands of regulatory interactions among thousands of genes, giving the first global view of the “control system” of cells and tissues. We found that genetic variants associated with human diseases disrupt components of these networks in disease-relevant tissues, giving new insights on disease mechanisms, which may lead to personalised treatments that are more effective and have fewer side effects. The paper is published in Nature Methods.
CBG director Sven Bergmann was interviewed in the Quarks & Co science show on the German TV channel WDR. The TV host wanted to know whether there are such things as German genes. The answer can be seen in the show .
We recently published Pascal (Pathway scoring algorithm), a tool that allows gene and pathway-level analysis of GWAS association results without the need to access the original genotypic data. Pascal was designed to be fast, accurate and to have high power to detect relevant pathways. We extensively tested our approach on a large collection of real GWAS association results and saw better discovery of confirmed pathways than with other popular methods. The paper is available in Plos Computational Biology .
We recently collaborated with the Hafen group in Zurich on a project to identify natural variants impacting size in Drosophila. We found an association in the kek1 locus, a well-characterized growth regulator. Additionally 33 novel loci were validated. The paper is available in Plos Genetics .
Together with the lab of Sophie Martin at DMF, we showed that the intracellular gradient of Pom1 in fission yeast achieves robustness to fluctuation through intermolecular auto-phosphorylation. Gradient robustness, how molecular gradient can convey precise positional information despite large fluctuations in molecular dynamics, has been the subject of many conjectures in the last decades. In particular it was hypothesized in 2003 that such robustness could be achieved by super-linear decay. In this work we show that in the Pom1 gradient, super-linear decay is obtained by a very simple and elegant mechanism namely intermolecular auto-phosphorylation. This provides a first telling example of gradient robustness through super-linear decay through auto-catalysis, which could be a widespread phenomenon. The paper is available in in Molecular Systems Biology.
Plants such as Arabidopsis Thaliana orient towards the light, thus optimizing the source of energy. This so-called phototropic response is mediated by the formation of a gradient of the plant growth hormone auxin. Using computational models validated by biological experiments, we showed in collaboration with the group of Christian Fankhauser from the CIG at UNIL, that the proton pump plays a crucial role in the establishment of this gradient and that this pump is regulated by the plants photoreceptors. The paper has just been published and is available in Molecular Systems Biology
In a joint work with the lab of Christian Fankhauser at CIG, UNIL, we showed that plants adapt their hormonal signal to the availability of resources when avoiding shade. If resources are scarce, the signal is weaker but the sensitivity is enhanced but when the signal is abundant, a stronger and more robust signal is produced. Our study, which thus suggests that the plant optimizes a signal cost-to-robustness trade-off, has just been published in PNAS.
In a study initiated by Sébastien Jacquemont from the Service of Medical Genetics in collaboration with the group of Evan Eichler, we investigated the CNV burden of autistic patients and close relatives. We could show that females diagnosed with autism have on average more deleterious mutations in genes involved in neuro-developmental disorders than males, hinting that women can cope with a higher mutational burden than men. Moreover most of the deleterious mutations in genes important for brain function are transmitted by the non-affected mothers, showing that they can tolerate more mutations than the fathers. This study was published in the American Journal of Human Genetics and featured in the French newspaper Le Figaro and in the Economist . The paper was awarded the neuroscience award from the French scientific magazine La Recherche . This yearly award rewards outstanding papers published by French speaking scientists in 12 different disciplines ranging from archeology to engineering.
In collaboration with the group of Sophie Martin from DMF (UNIL), we developed Cellophane, an ImageJ plugin that semi-automatically quantifies fluorescent protein concentration profiles along the cell cortex. This plugin enabled the quantification of hundreds of profiles of two key regulators of the fission yeast cell cycle, Pom2 and Cdr2. The data analysis, along with other experimental evidence, showed that two important functions of Pom1, deciding when and where to divide, require distinct levels of Pom1. Lower Pom1 level are sufficient for division positioning, but higher levels are required to delay mitotic entry until the proper size is reached. The paper has been published in Cell Cycle .
Together with the group of Christian Fankhauser from the CIG at UNIL, CBG post-doc Tim Hohm showed that the sites of light perception for phototropism is located in the upper hypocotyl, where asymmetric elongation occurs. Thus, in contrast to monocots where a phototropism signal is sent from the leaves to the stem, in Arabidopsis it all happens "on site". The paper has been published in Current Biology
In collaboration with the group of Christian Fankhauser at CIG, UNIL, we developed the HypoPhen software for the high throughput quantification of seedling elongation and bending from time-lapsed images. Using this tool, hundreds of Arabidopsis seedlings were measured to show that phytochrome A in the nucleus is important for phototropism. The results have been published in Plant Cell on February 28 2012.
A genome-wide association study by the HYPERGENES Consortium unravelled a novel hypertension susceptibility locus in the promoter region of the eNOS gene and essential hypertension. The article appeared online in Hypertension on 19 December 2011.
In a recent work, we developed a general formalism allowing to model diffusive gradient formation from an arbitrary source. This formalism applies to various diffusion problems and we illustrate our theory with the explicit example of the Bicoid gradient establishment in Drosophila embryos. The article appeared online in Journal of Theoretical Biology on 10 November 2011.
On June 25 2010, during the 8th [BC]2 Computational Biology Conference in Basel, SIB Swiss Institute of Bioinformatics announced that CBG member [[Aitana Morton de Lachapelle]] is the winner of the SIB Young Bioinformatician Award 2010.
Our calcium meta-analysis paper was published in PLoS Genetics.
We published an application note about the ExpressionView bicluster visualization tool in Bioinformatics. Please see the [[ExpressionView]] page for more — documentation, downloads, screenshots — on ExpressionView.
In collaboration with Mehdi Tafti's research group we have published our recent discovery on a newly identified HLA haplotype that protects individuals from narcolepsy even if they carry the famous risk haplotype. Our article appeared online in Nature Genetics on 15 August 2010.
Via the CoLaus and Hypergenes cohorts our group contributed to the meta-analysis of the GIANT consortium that revealed hundreds of genetic variants associated with human height; 18 new loci for body mass index; and 13 new loci for waist-hip-ratio.
In collaboration with John Whittaker (GSK) we have published a new methodology to infer total explained variance of [[Genome Wide Association Studies | GWAS]] hits. Our method was applied to the most recent GIANT association summary statistics and revealed that GWAS hits explain at least 30% of human height variations. The article appeared online in Genetic Epidemiology on 6 April 2011.
In collaboration with the Basler group (University of Zurich), we developed a theoretical model allowing to understand which is the leading mechanism involved in the Dpp long range gradient formation. The article appeared online in PLoS Biology on 26 July 2011.
A collaborative study with the Kaessmann group on "The evolution of gene expression levels in mammalian organs" where we first applied the [[ISA]] to RNAseq data has been published online as article in Nature on 19 October 2011.
Sven Bergmann has successfully completed his tenure-track as Assistant Professor and is Associate Professor since August 2010.