Mesoscale modelling of North Sea wind resources with COSMO-CLM: model evaluation and impact assessment of future wind farm characteristics on cluster-scale wake losses

As many coastal regions experience a rapid increase in offshore wind farm installations, inter-farm distances become smaller, with a tendency to install larger turbines at high capacity densities. It is, however, not clear how the wake losses in wind farm clusters depend on the characteristics and spacing of the individual wind farms. Here, we...

Learning for Control: An Inverse Optimization Approach

We present a learning method to learn the mapping from an input space to an action space, which is particularly suitable when the action is an optimal decision with respect to a certain unknown cost function. We use an inverse optimization approach to retrieve the cost function by introducing a new loss function and a new hypothesis class of...

Multiplexed Cas9 targeting reveals genomic location effects and gRNA-based staggered breaks influencing mutation efficiency

Understanding the impact of guide RNA (gRNA) and genomic locus on CRISPR-Cas9 activity is crucial to design effective gene editing assays. However, it is challenging to profile Cas9 activity in the endogenous cellular environment. Here we leverage our TRIP technology to integrate ~ 1k barcoded reporter genes in the genomes of mouse embryonic...

3D hotspots of recurrent retroviral insertions reveal long-range interactions with cancer genes

Genomically distal mutations can contribute to the deregulation of cancer genes by engaging in chromatin interactions. To study this, we overlay viral cancer-causing insertions obtained in a murine retroviral insertional mutagenesis screen with genome-wide chromatin conformation capture data. Here we find that insertions tend to cluster in 3D...

Chromatin Landscapes of Retroviral and Transposon Integration Profiles

The ability of retroviruses and transposons to insert their genetic material into host DNA makes them widely used tools in molecular biology, cancer research and gene therapy. However, these systems have biases that may strongly affect research outcomes. To address this issue, we generated very large datasets consisting of to unselected...

Analysis of tumor heterogeneity and cancer gene networks using deep sequencing of MMTV-induced mouse mammary tumors

Cancer develops through a multistep process in which normal cells progress to malignant tumors via the evolution of their genomes as a result of the acquisition of mutations in cancer driver genes. The number, identity and mode of action of cancer driver genes, and how they contribute to tumor evolution is largely unknown. This study deployed...