Enhanced Operational Semantics in Systems Biology

We are faced with a great challenge: the cross-fertilization between the fields of formal methods for concurrency, in the computer science domain, and systems biology in the biological realm

On Deterministic Sketching and Streaming for Sparse Recovery and Norm Estimation

We study classic streaming and sparse recovery problems using deterministic linear sketches, including l1/l1 and linf/l1 sparse recovery problems (the latter also being known as l1-heavy hitters), norm estimation, and approximate inner product. We focus on devising a fixed matrix A in R^{m x n} and a deterministic recovery/estimation procedure which work for all possible input vectors simultaneously. Our results improve upon existing work, the following being our main contributions: * A proof that linf/l1 sparse recovery and inner product estimation are equivalent, and that incoherent matrices can be used to solve both problems. Our upper bound for the number of measurements is m=O(eps^{-2}*min{log n, (log n / log(1/eps))^2}). We can also obtain fast sketching and recovery algorithms by making use of the Fast Johnson-Lindenstrauss transform. Both our running times and number of measurements improve upon previous work. We can also obtain better error guarantees than previous work in terms of a smaller tail of the input vector. * A new lower bound for the number of linear measurements required to solve l1/l1 sparse recovery. We show Omega(k/eps^2 + klog(n/k)/eps) measurements are required to recover an x' with |x - x'|_1 <= (1+eps)|x_{tail(k)}|_1, where x_{tail(k)} is x projected onto all but its largest k coordinates in magnitude. * A tight bound of m = Theta(eps^{-2}log(eps^2 n)) on the number of measurements required to solve deterministic norm estimation, i.e., to recover |x|_2 +/- eps|x|_1. For all the problems we study, tight bounds are already known for the randomized complexity from previous work, except in the case of l1/l1 sparse recovery, where a nearly tight bound is known. Our work thus aims to study the deterministic complexities of these problems

Elasticity and Petri nets

Digital electronic systems typically use synchronous clocks and primarily assume fixed duration of their operations to simplify the design process. Time elastic systems can be constructed either by replacing the clock with communication handshakes (asynchronous version) or by augmenting the clock with a synchronous version of a handshake (synchronous version). Time elastic systems can tolerate static and dynamic changes in delays (asynchronous case) or latencies (synchronous case) of operations that can be used for modularity, ease of reuse and better power-delay trade-off. This paper describes methods for the modeling, performance analysis and optimization of elastic systems using Marked Graphs and their extensions capable of describing behavior with early evaluation. The paper uses synchronous elastic systems (aka latency-tolerant systems) for illustrating the use of Petri nets, however, most of the methods can be applied without changes (except changing the delay model associated with events of the system) to asynchronous elastic systems.Peer ReviewedPostprint (author's final draft

Efficient Reconstruction of Metabolic Pathways by Bidirectional Chemical Search

One of the main challenges in systems biology is the establishment of the metabolome: a catalogue of the metabolites and biochemical reactions present in a specific organism. Current knowledge of biochemical pathways as stored in public databases such as KEGG, is based on carefully curated genomic evidence for the presence of specific metabolites and enzymes that activate particular biochemical reactions. In this paper, we present an efficient method to build a substantial portion of the artificial chemistry defined by the metabolites and biochemical reactions in a given metabolic pathway, which is based on bidirectional chemical search. Computational results on the pathways stored in KEGG reveal novel biochemical pathways

Perspective: Dietary Biomarkers of Intake and Exposure - Exploration with Omics Approaches

While conventional nutrition research has yielded biomarkers such as doubly labeled water for energy metabolism and 24-h urinary nitrogen for protein intake, a critical need exists for additional, equally robust biomarkers that allow for objective assessment of specific food intake and dietary exposure. Recent advances in high-throughput MS combined with improved metabolomics techniques and bioinformatic tools provide new opportunities for dietary biomarker development. In September 2018, the NIH organized a 2-d workshop to engage nutrition and omics researchers and explore the potential of multiomics approaches in nutritional biomarker research. The current Perspective summarizes key gaps and challenges identified, as well as the recommendations from the workshop that could serve as a guide for scientists interested in dietary biomarkers research. Topics addressed included study designs for biomarker development, analytical and bioinformatic considerations, and integration of dietary biomarkers with other omics techniques. Several clear needs were identified, including larger controlled feeding studies, testing a variety of foods and dietary patterns across diverse populations, improved reporting standards to support study replication, more chemical standards covering a broader range of food constituents and human metabolites, standardized approaches for biomarker validation, comprehensive and accessible food composition databases, a common ontology for dietary biomarker literature, and methodologic work on statistical procedures for intake biomarker discovery. Multidisciplinary research teams with appropriate expertise are critical to moving forward the field of dietary biomarkers and producing robust, reproducible biomarkers that can be used in public health and clinical research

Studies on the genetic basis of resistance to potato leaf roll virus, potato virus Y and potato virus X in Solanum brevidens using somatic hybrids of Solanum brevidens and Solanum tuberosum

Amongst tetrapoid somatic hybrids of Solanum tuberosum and Solanum brevidens, the expression of resistance to potato virus X (PVX), potato virus Y (PVY) and potato leaf roll virus (PLRV) ranged between that of the fusion parents. Genotypes with general morphology resembling S. brevidens generally were more resistant to virus infection. In contrast, hexaploid hybrids could be divided into high and low resistance groups, resistance being associated with two doses of the S. brevidens nuclear genome, but again genotypes with general morphology resembling S. brevidens were more resistance. Correlation of resistance to the different viruses was observed in aneuploid hybrids lacking parental chromosomes. This observation suggests that resistance/susceptibility is associated with the loss of individual S. brevidens or S. tuberosum chromosomes

Broad spectrum virus resistance in Solanum brevidens and its introduction by protoplast fusion to cultivated potato

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