Postdoc – Multi-Omics and Translational Statistics

Predicting genotype-phenotype relationships in health and disease through large-scale phenotyping and multi-omics

Postdoctoral research positions are available in the group of Wolfgang Huber at EMBL Heidelberg for energetic and creative researchers in the areas of biomedical data science and statistical computing. Apply if you are driven by method development for novel technologies in personalized medicine and systems genetics, or by making biological or medical discoveries through novel ways of integrating large multi-omic and phenotypic data. An excellent network of biomedical and technological collaborations, including the EC Project SOUND, offers novel data types and datasets, as well as opportunities for discovery validation and translation by domain experts.

Context

The European Molecular Biology Laboratory (EMBL) is one of the highest ranked scientific research organisations in the world. The Headquarters Laboratory is located in Heidelberg (Germany), with additional sites in Cambridge (UK), Grenoble (France), Hamburg (Germany) and Rome (Italy).

SOUND is an international research project funded by the European Commission (EC) within its Horizon 2020 Research and Innovation programme “Personalizing Health and Care”. Its objective is to create the bioinformatic tools for statistically informed use of personal genomes and other types of ‘omic data (multi-omics) in medicine, including cancers and rare metabolic diseases. Coordinated at EMBL by W. Huber, it comprises partners from top research institutions including Cambridge, Munich, Zurich, Heidelberg and Lisbon, and is running from September 2015.

Bioconductor is an open source, open development software project to collaboratively develop tools for the analysis and comprehension of high-throughput genomic data. The Bioconductor core team is a partner in SOUND, and many SOUND partners are active contributors.

Qualifications and experience

The position requires outstanding quantitative and analytical skills. We are looking for candidates with PhD-level expertise in genomics, statistics, mathematics, physics, computational biology or related fields, who are looking to make an impact in biomedical research, as well as for candidates with a biomedical background and exceptional quantitative skills. Curiosity to work in interdisciplinary projects and continuously expand your expertise is expected. Experience in large-scale data analysis will be useful, and proficiency in computer programming (e.g. R) is required. An appropriate record of productivity (evidenced e.g. by academic papers or scientific software) is expected. The position requires the ability to independently take responsibility over your project, strong teamwork and communication skills, reliability, attention to detail and effective time management.

Please contact Wolfgang Huber (http://www.huber.embl.de) for questions.

Additional Information

EMBL is an inclusive, equal opportunity employer offering attractive conditions and benefits appropriate to an international research organisation.

New paper: Single-cell transcriptome analysis reveals coordinated ectopic gene-expression patterns in medullary thymic epithelial cells

Abstract: Expression of tissue-restricted self antigens (TRAs) in medullary thymic epithelial cells (mTECs) is essential for the induction of self-tolerance and prevents autoimmunity, with each TRA being expressed in only a few mTECs. How this process is regulated in single mTECs and is coordinated at the population level, such that the varied single-cell patterns add up to faithfully represent TRAs, is poorly understood. Here we used single-cell RNA sequencing and obtained evidence of numerous recurring TRA–co- expression patterns, each present in only a subset of mTECs. Co-expressed genes clustered in the genome and showed enhanced chromatin accessibility. Our findings characterize TRA expression in mTECs as a coordinated process that might involve local remodeling of chromatin and thus ensures a comprehensive representation of the immunological self.

Read more: Brennecke et al.ni2015

New paper: A map of directional genetic interactions in a metazoan cell

Abstract: Gene-gene interactions shape complex phenotypes and modify the effects of mutations during development and disease. The effects of statistical gene-gene interactions on phenotypes have been used to assign genes to functional modules. However, directional, epistatic interactions, which reflect regulatory relationships between genes, have been challenging to map at large-scale. Here, we used combinatorial RNA interference and automated single-cell phenotyping to generate a large genetic interaction map for 21 phenotypic features of Drosophila cells. We devised a method that combines genetic interactions on multiple phenotypes to reveal directional relationships. This network reconstructed the sequence of protein activities in mitosis. Moreover, it revealed that the Ras pathway interacts with the SWI/SNF chromatin-remodelling complex, an interaction that we show is conserved in human cancer cells. Our study presents a powerful approach for reconstructing directional regulatory networks and provides a resource for the interpretation of functional consequences of genetic alterations.

Read more

Bioconductor project – Perspective paper

The Perspective paper Orchestrating high-throughput genomic analysis with Bioconductor is addressed at users and prospective developers. It gives an overview over the collaborative software development and delivery model of the Bioconductor project. At Readcube: http://rdcu.be/b2VE.

Abstract: Bioconductor is an open-source, open-development software project for the analysis and comprehension of high-throughput data in genomics and molecular biology. The project aims to enable interdisciplinary research, collaboration and rapid development of scientific software. Based on the statistical programming language R, Bioconductor comprises 934 interoperable packages contributed by a large, diverse community of scientists. Packages cover a range of bioinformatic and statistical applications. They undergo formal initial review and continuous automated testing. We present an overview for prospective users and contributors.