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Finding spanning trees under various constraints is a classic problem with applications in many fields. Recently, a novel notion of dense ( sparse ) tree, and in particular spanning tree (DST and SST respectively), is introduced as the structure that have a large (small) number of subtrees, or small (large) sum of distances between vertices. We show that finding DST and SST reduces to solving the discrete optimization problems. New and efficient approaches to find such spanning trees is achieved by imposing certain conditions on the vertex degrees which are then used to define an objective function that is minimized over all spanning trees of the graph under consideration. Solving this minimization problem exactly may be prohibitively time consuming for large graphs. Hence, we propose to use genetic algorithm (GA) which is one of well known metaheuristics methods to solve DST and SST approximately. As far as we are aware this is the first time GA has been used in this context.We also demonstrate on a number of applications that GA approach is well suited for these types of problems both in computational efficiency and accuracy of the approximate solution. Furthermore, we improve the efficiency of the proposed method by using Kruskal s algorithm in combination with GA. The application of our methods to several practical large graphs and networks is presented. Computational results show that they perform faster than previously proposed heuristic methods and produce more accurate solutions. Furthermore, the new feature of the proposed approach is that it can be applied recursively to sub-trees or spanning trees with additional constraints in order to further investigate the graphical properties of the graph and/or network. The application of this methodology on the gene network of a cancer cell led to isolating key genes in a network that were not obvious from previous studies.

Career athletes, active military, and head trauma victims are at increased risk for mild repetitive traumatic brain injury (rTBI), a condition that contributes to the development of epilepsy and neurodegenerative diseases. Standard clinical imaging fails to identify rTBI-induced lesions, and novel non-invasive methods are needed. Here, we evaluated if hyperpolarized 13C magnetic resonance spectroscopic imaging (HP 13C MRSI) could detect long-lasting changes in brain metabolism 3.5 months post-injury in a rTBI mouse model. Our results show that this metabolic imaging approach can detect changes in cortical metabolism at that timepoint, whereas multimodal MR imaging did not detect any structural or contrast alterations. Using Machine Learning, we further show that HP 13C MRSI parameters can help classify rTBI vs. Sham and predict long-term rTBI-induced behavioral outcomes. Altogether, our study demonstrates the potential of metabolic imaging to improve detection, classification and outcome prediction of previously undetected rTBI.

Characterization of decision-making in cells in response to received signals is of importance for understanding how cell fate is determined. The problem becomes multi-faceted and complex when we consider cellular heterogeneity and dynamics of biochemical processes. In this paper, we present a unified set of decision-theoretic, machine learning and statistical signal processing methods and metrics to model the precision of signaling decisions, in the presence of uncertainty, using single cell data. First, we introduce erroneous decisions that may result from signaling processes and identify false alarms and miss events associated with such decisions. Then, we present an optimal decision strategy which minimizes the total decision error probability. Additionally, we demonstrate how graphing receiver operating characteristic curves conveniently reveals the trade-off between false alarm and miss probabilities associated with different cell responses. Furthermore, we extend the introduced framework to incorporate the dynamics of biochemical processes and reactions in a cell, using multi-time point measurements and multi-dimensional outcome analysis and decision-making algorithms. The introduced multivariate signaling outcome modeling framework can be used to analyze several molecular species measured at the same or different time instants. We also show how the developed binary outcome analysis and decision-making approach can be extended to more than two possible outcomes. As an example and to show how the introduced methods can be used in practice, we apply them to single cell data of PTEN, an important intracellular regulatory molecule in a p53 system, in wild-type and abnormal cells. The unified signaling outcome modeling framework presented here can be applied to various organisms ranging from viruses, bacteria, yeast and lower metazoans to more complex organisms such as mammalian cells. Ultimately, this signaling outcome modeling approach can be utilized to better understand the transition from physiological to pathological conditions such as inflammation, various cancers and autoimmune diseases.

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