Natural similarity measures between position frequency matrices with an application to clustering

Motivation: Transcription factors (TFs) play a key role in gene regulation by binding to target sequences. In silico prediction of potential binding of a TF to a binding site is a well-studied problem in computational biology. The binding sites for one TF are represented by a position frequency matrix (PFM). The discovery of new PFMs requires the comparison to known PFMs to avoid redundancies. In general, two PFMs are similar if they occur at overlapping positions under a null model. Still, most existing methods compute similarity according to probabilistic distances of the PFMs. Here we propose a natural similarity measure based on the asymptotic covariance between the number of PFM hits incorporating both strands. Furthermore, we introduce a second measure based on the same idea to cluster a set of the Jaspar PFMs. Results: We show that the asymptotic covariance can be efficiently computed by a two dimensional convolution of the score distributions. The asymptotic covariance approach shows strong correlation with simulated data. It outperforms three alternative methods. The Jaspar clustering yields distinct groups of TFs of the same class. Furthermore, a representative PFM is given for each class. In contrast to most other clustering methods, PFMs with low similarity automatically remain singletons. Availability: A website to compute the similarity and to perform clustering, the source code and Supplementary Material are available at http://mosta.molgen.mpg.d

3D Cancer Models: The Need for a Complex Stroma, Compartmentalization and Stiffness

The use of tissue-engineered 3D models of cancer has grown in popularity with recent advances in the field of cancer research. 3D models are inherently more biomimetic compared to 2D cell monolayers cultured on tissue-culture plastic. Nevertheless 3D models still lack the cellular and matrix complexity of native tissues. This review explores different 3D models currently used, outlining their benefits and limitations. Specifically, this review focuses on stiffness and collagen density, compartmentalization, tumor-stroma cell population and extracellular matrix composition. Furthermore, this review explores the methods utilized in different models to directly measure cancer invasion and growth. Of the models evaluated, with PDX and in vivo as a relative "gold standard", tumoroids were deemed as comparable 3D cancer models with a high degree of biomimicry, in terms of stiffness, collagen density and the ability to compartmentalize the tumor and stroma. Future 3D models for different cancer types are proposed in order to improve the biomimicry of cancer models used for studying disease progression

Mission activities planning for a Hermes mission by means of AI-technology

Mission Activities Planning is a complex task to be performed by mission control centers. AI technology can offer attractive solutions to the planning problem. This paper presents the use of a new AI-based Mission Planning System for crew activity planning. Based on a HERMES servicing mission to the COLUMBUS Man Tended Free Flyer (MTFF) with complex time and resource constraints, approximately 2000 activities with 50 different resources have been generated, processed, and planned with parametric variation of operationally sensitive parameters. The architecture, as well as the performance of the mission planning system, is discussed. An outlook to future planning scenarios, the requirements, and how a system like MARS can fulfill those requirements is given