Visual Collaboration Leader-Follower UAV-Formation for Indoor Exploration.

UAVs operating in a leader-follower formation demand the knowledge of the relative pose between the collaborating members. This necessitates the RF-communication of this information which increases the communication latency and can easily result in lost data packets. In this work, rather than relying on this autopilot data exchange, a visual scheme using passive markers is presented. Each formation-member carries passive markers in a RhOct configuration. These markers are visually detected and the relative pose of the members is on-board determined, thus eliminating the need for RF-communication. A reference path is then evaluated for each follower that tracks the leader and maintains a constant distance between the formation-members. Experimental studies show a mean position detection error (5 × 5 × 10cm) or less than 0.0031% of the available workspace [0.5 up to 5m, 50.43° × 38.75° Field of View (FoV)]. The efficiency of the suggested scheme against varying delays are examined in these studies, where it is shown that a delay up to 1.25s can be tolerated for the follower to track the leader as long as the latter one remains within its FoV.

Predicting the evolution of Escherichia coli by a data-driven approach.

A tantalizing question in evolutionary biology is whether evolution can be predicted from past experiences. To address this question, we created a coherent compendium of more than 15,000 mutation events for the bacterium Escherichia coli under 178 distinct environmental settings. Compendium analysis provides a comprehensive view of the explored environments, mutation hotspots and mutation co-occurrence. While the mutations shared across all replicates decrease with the number of replicates, our results argue that the pairwise overlapping ratio remains the same, regardless of the number of replicates. An ensemble of predictors trained on the mutation compendium and tested in forward validation over 35 evolution replicates achieves a 49.2 ± 5.8% (mean ± std) precision and 34.5 ± 5.7% recall in predicting mutation targets. This work demonstrates how integrated datasets can be harnessed to create predictive models of evolution at a gene level and elucidate the effect of evolutionary processes in well-defined environments.

From data to optimal decision making: a data-driven, probabilistic machine learning approach to decision support for patients with sepsis.

BACKGROUND: A tantalizing question in medical informatics is how to construct knowledge from heterogeneous datasets, and as an extension, inform clinical decisions. The emergence of large-scale data integration in electronic health records (EHR) presents tremendous opportunities. However, our ability to efficiently extract informed decision support is limited due to the complexity of the clinical states and decision process, missing data and lack of analytical tools to advice based on statistical relationships. OBJECTIVE: Development and assessment of a data-driven method that infers the probability distribution of the current state of patients with sepsis, likely trajectories, optimal actions related to antibiotic administration, prediction of mortality and length-of-stay. METHODS: We present a data-driven, probabilistic framework for clinical decision support in sepsis-related cases. We first define states, actions, observations and rewards based on clinical practice, expert knowledge and data representations in an EHR dataset of 1492 patients. We then use Partially Observable Markov Decision Process (POMDP) model to derive the optimal policy based on individual patient trajectories and we evaluate the performance of the model-derived policies in a separate test set. Policy decisions were focused on the type of antibiotic combinations to administer. Multi-class and discriminative classifiers were used to predict mortality and length of stay. RESULTS: Data-derived antibiotic administration policies led to a favorable patient outcome in 49% of the cases, versus 37% when the alternative policies were followed (P=1.3e-13). Sensitivity analysis on the model parameters and missing data argue for a highly robust decision support tool that withstands parameter variation and data uncertainty. When the optimal policy was followed, 387 patients (25.9%) have 90% of their transitions to better states and 503 patients (33.7%) patients had 90% of their transitions to worse states (P=4.0e-06), while in the non-policy cases, these numbers are 192 (12.9%) and 764 (51.2%) patients (P=4.6e-117), respectively. Furthermore, the percentage of transitions within a trajectory that lead to a better or better/same state are significantly higher by following the policy than for non-policy cases (605 vs 344 patients, P=8.6e-25). Mortality was predicted with an AUC of 0.7 and 0.82 accuracy in the general case and similar performance was obtained for the inference of the length-of-stay (AUC of 0.69 to 0.73 with accuracies from 0.69 to 0.82). CONCLUSIONS: A data-driven model was able to suggest favorable actions, predict mortality and length of stay with high accuracy. This work provides a solid basis for a scalable probabilistic clinical decision support framework for sepsis treatment that can be expanded to other clinically relevant states and actions, as well as a data-driven model that can be adopted in other clinical areas with sufficient training data.

A systems biology analysis of brain microvascular endothelial cell lipotoxicity.

BACKGROUND: Neurovascular inflammation is associated with a number of neurological diseases including vascular dementia and Alzheimer's disease, which are increasingly important causes of morbidity and mortality around the world. Lipotoxicity is a metabolic disorder that results from accumulation of lipids, particularly fatty acids, in non-adipose tissue leading to cellular dysfunction, lipid droplet formation, and cell death. RESULTS: Our studies indicate for the first time that the neurovascular circulation also can manifest lipotoxicity, which could have major effects on cognitive function. The penetration of integrative systems biology approaches is limited in this area of research, which reduces our capacity to gain an objective insight into the signal transduction and regulation dynamics at a systems level. To address this question, we treated human microvascular endothelial cells with triglyceride-rich lipoprotein (TGRL) lipolysis products and then we used genome-wide transcriptional profiling to obtain transcript abundances over four conditions. We then identified regulatory genes and their targets that have been differentially expressed through analysis of the datasets with various statistical methods. We created a functional gene network by exploiting co-expression observations through a guilt-by-association assumption. Concomitantly, we used various network inference algorithms to identify putative regulatory interactions and we integrated all predictions to construct a consensus gene regulatory network that is TGRL lipolysis product specific. CONCLUSION: System biology analysis has led to the validation of putative lipid-related targets and the discovery of several genes that may be implicated in lipotoxic-related brain microvascular endothelial cell responses. Here, we report that activating transcription factors 3 (ATF3) is a principal regulator of TGRL lipolysis products-induced gene expression in human brain microvascular endothelial cell.

An integrative, multi-scale, genome-wide model reveals the phenotypic landscape of Escherichia coli.

Given the vast behavioral repertoire and biological complexity of even the simplest organisms, accurately predicting phenotypes in novel environments and unveiling their biological organization is a challenging endeavor. Here, we present an integrative modeling methodology that unifies under a common framework the various biological processes and their interactions across multiple layers. We trained this methodology on an extensive normalized compendium for the gram-negative bacterium Escherichia coli, which incorporates gene expression data for genetic and environmental perturbations, transcriptional regulation, signal transduction, and metabolic pathways, as well as growth measurements. Comparison with measured growth and high-throughput data demonstrates the enhanced ability of the integrative model to predict phenotypic outcomes in various environmental and genetic conditions, even in cases where their underlying functions are under-represented in the training set. This work paves the way toward integrative techniques that extract knowledge from a variety of biological data to achieve more than the sum of their parts in the context of prediction, analysis, and redesign of biological systems.

SBROME: a scalable optimization and module matching framework for automated biosystems design.

The development of a scalable framework for biodesign automation is a formidable challenge given the expected increase in part availability and the ever-growing complexity of synthetic circuits. To allow for (a) the use of previously constructed and characterized circuits or modules and (b) the implementation of designs that can scale up to hundreds of nodes, we here propose a divide-and-conquer Synthetic Biology Reusable Optimization Methodology (SBROME). An abstract user-defined circuit is first transformed and matched against a module database that incorporates circuits that have previously been experimentally characterized. Then the resulting circuit is decomposed to subcircuits that are populated with the set of parts that best approximate the desired function. Finally, all subcircuits are subsequently characterized and deposited back to the module database for future reuse. We successfully applied SBROME toward two alternative designs of a modular 3-input multiplexer that utilize pre-existing logic gates and characterized biological parts.