MOTIVATION: Recapitulating aspects of human organ functions using in vitro (e.g. plates, transwells, etc.), in vivo (e.g. mouse, rat, etc.), or ex vivo (e.g. organ chips, 3D systems, etc.) organ models is of paramount importance for drug discovery and precision medicine. It will allow us to identify potential side effects and test the effectiveness of new therapeutic approaches early in their design phase, and will inform the development of better disease models. Developing mathematical methods to reliably compare the 'distance/similarity' of organ models from/to the real human organ they represent is an understudied problem with important applications in biomedicine and tissue engineering. RESULTS: We introduce the Transcriptomic Signature Distance (TSD), an information-theoretic distance for assessing the transcriptomic similarity of two tissue samples, or two groups of tissue samples. In developing TSD, we are leveraging next-generation sequencing data as well as information retrieved from well-curated databases providing signature gene sets characteristic for human organs. We present the justification and mathematical development of the new distance and demonstrate its effectiveness and advantages in different scenarios of practical importance using several publicly available RNA-seq datasets. AVAILABILITY AND IMPLEMENTATION: The computation of both TSD versions (simple and weighted) has been implemented in R and can be downloaded from https://github.com/Cod3B3nd3R/Transcriptomic-Signature-Distance. CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Integration of data from different modalities is a necessary step for multi-scale data analysis in many fields, including biomedical research and systems biology. Directed graphical models offer an attractive tool for this problem because they can represent both the complex, multivariate probability distributions and the causal pathways influencing the system. Graphical models learned from biomedical data can be used for classification, biomarker selection and functional analysis, while revealing the underlying network structure and thus allowing for arbitrary likelihood queries over the data. RESULTS: In this paper, we present and test new methods for finding directed graphs over mixed data types (continuous and discrete variables). We used this new algorithm, CausalMGM, to identify variables directly linked to disease diagnosis and progression in various multi-modal datasets, including clinical datasets from chronic obstructive pulmonary disease (COPD). COPD is the third leading cause of death and a major cause of disability and thus determining the factors that cause longitudinal lung function decline is very important. Applied on a COPD dataset, mixed graphical models were able to confirm and extend previously described causal effects and provide new insights on the factors that potentially affect the longitudinal lung function decline of COPD patients. AVAILABILITY AND IMPLEMENTATION: The CausalMGM package is available on http://www.causalmgm.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Motivation: Learning probabilistic graphs over mixed data is an important way to combine gene expression and clinical disease data. Leveraging the existing, yet imperfect, information in pathway databases for mixed graphical model (MGM) learning is an understudied problem with tremendous potential applications in systems medicine, the problems of which often involve high-dimensional data. Results: We present a new method, piMGM, which can learn with accuracy the structure of probabilistic graphs over mixed data by appropriately incorporating priors from multiple experts with different degrees of reliability. We show that piMGM accurately scores the reliability of prior information from a given expert even at low sample sizes. The reliability scores can be used to determine active pathways in healthy and disease samples. We tested piMGM on both simulated and real data from TCGA, and we found that its performance is not affected by unreliable priors. We demonstrate the applicability of piMGM by successfully using prior information to identify pathway components that are important in breast cancer and improve cancer subtype classification. Availability and implementation: http://www.benoslab.pitt.edu/manatakisECCB2018.html. Supplementary information: Supplementary data are available at Bioinformatics online.

There is a fast growing interest in exploiting wireless sensor networks (WSNs) for tracking the boundaries and predicting the evolution properties of diffusive hazardous phenomena (e.g. wildfires, oil slicks etc.) often modeled as “continuous objects”. We present a novel distributed algorithm for estimating and tracking the local evolution characteristics of continuous objects. The hazard's front line is approximated as a set of line segments, and the spatiotemporal evolution of each segment is modeled by a small number of parameters (orientation, direction and speed of motion). As the hazard approaches, these parameters are re-estimated using ad-hoc clusters (triplets) of collaborating sensor nodes. Parameters updating is based on algebraic closed-form expressions resulting from the analytical solution of a Bayesian estimation problem. Therefore, it can be implemented by microprocessors of the WSN nodes, while respecting their limited processing capabilities and strict energy constraints. Extensive computer simulations demonstrate the ability of the proposed distributed algorithm to estimate accurately the evolution characteristics of complex hazard fronts under different conditions by using reasonably dense WSNs. The proposed in-network processing scheme does not require sensor node clocks synchronization and is shown to be robust to sensor node failures and communication link failures, which are expected in harsh environments.

Assessing how the performance of a decentralized wireless sensor network (WSN) algorithm's implementation scales, in terms of communication and energy costs, as the network size increases is an essential requirement before its field deployment. Simulations are commonly used for this purpose, especially for large-scale environmental monitoring applications. However, it is difficult to evaluate energy consumption, processing and memory requirements before the algorithm is really ported to a real WSN platform. We propose a method for emulating the operation of collaborative algorithms in large-scale WSNs by re-using a small number of available real sensor nodes. We demonstrate the potential of the proposed simulation-driven WSN emulation approach by using it to estimate how communication and energy costs scale with the network's size when implementing a collaborative algorithm we developed in [12] for tracking the spatiotemporal evolution of a progressing environmental hazard.

Predicting accurately the spatiotemporal evolution of a diffusive environmental hazard is of paramount importance for its effective containment. We approximate the front line of a hazard with a set of line segments (local front models). We model the progression characteristics of these front segments by appropriately modified 2D Gaussian functions. The modified Gaussian model parameters are adjusted based on the solution of a Kullback-Leibler (KL) divergence minimization problem. The whole scheme can be realized by a wireless sensor network by forming dynamically triplets of cooperating sensor nodes along the path of the hazard. It is shown that the algorithm can track effectively the front characteristics (in terms of direction and speed) even in the presence of faulty sensor nodes.

We present a novel decentralized Wireless Sensor Network (WSN) algorithm which can estimate both the speed and direction of an evolving diffusive hazardous phenomenon (e.g. a wildfire, oil spill, etc.). In the proposed scheme we approximate a progressing hazard's front as a set of line segments. The spatiotemporal evolution of each line segment is modeled by a modified 2D Gaussian function. As the phenomenon evolves, the parameters of this model are updated based on the analytical solution of a Kullback - Leibler (KL) divergence minimization problem. This leads to an efficient WSN distributed parameters estimation algorithm that can be implemented by dynamically formed clusters (triplets) of collaborating sensor nodes. Computer simulations show that our approach is able to track the evolving phenomenon with reasonable accuracy even if a percentage of sensors fails due to the hazard and/or the phenomenon has a time varying speed.