mspire: mass spectrometry proteomics in Ruby

Summary: Mass spectrometry-based proteomics stands to gain from additional analysis of its data, but its large, complex datasets make demands on speed and memory usage requiring special consideration from scripting languages. The software library ‘mspire’—developed in the Ruby programming language—offers quick and memory-efficient readers for standard xml proteomics formats, converters for intermediate file types in typical proteomics spectral-identification work flows (including the Bioworks .srf format), and modules for the calculation of peptide false identification rates

An ALM model for pension funds using integrated chance constraints

We discuss integrated chance constraints in their role of short-term risk constraints in a strategic ALM model for Dutch pension funds. The problem is set up as a multistage recourse model, with special attention for modeling short-term risk prompted by the development of new guidelines by the regulating authority for Dutch pension funds. The paper concludes with a numerical illustration of the importance of such short-term risk constraints

Models for Minimax Stochastic Linear Optimization Problems with Risk Aversion

We propose a semidefinite optimization (SDP) model for the class of minimax two-stage stochastic linear optimization problems with risk aversion. The distribution of second-stage random variables belongs to a set of multivariate distributions with known first and second moments. For the minimax stochastic problem with random objective, we provide a tight SDP formulation. The problem with random right-hand side is NP-hard in general. In a special case, the problem can be solved in polynomial time. Explicit constructions of the worst-case distributions are provided. Applications in a production-transportation problem and a single facility minimax distance problem are provided to demonstrate our approach. In our experiments, the performance of minimax solutions is close to that of data-driven solutions under the multivariate normal distribution and better under extremal distributions. The minimax solutions thus guarantee to hedge against these worst possible distributions and provide a natural distribution to stress test stochastic optimization problems under distributional ambiguity.Singapore-MIT Alliance for Research and TechnologyNational University of Singapore. Dept. of Mathematic

On the Power of Robust Solutions in Two-Stage Stochastic and Adaptive Optimization Problems

We consider a two-stage mixed integer stochastic optimization problem and show that a static robust solution is a good approximation to the fully adaptable two-stage solution for the stochastic problem under fairly general assumptions on the uncertainty set and the probability distribution. In particular, we show that if the right-hand side of the constraints is uncertain and belongs to a symmetric uncertainty set (such as hypercube, ellipsoid or norm ball) and the probability measure is also symmetric, then the cost of the optimal fixed solution to the corresponding robust problem is at most twice the optimal expected cost of the two-stage stochastic problem. Furthermore, we show that the bound is tight for symmetric uncertainty sets and can be arbitrarily large if the uncertainty set is not symmetric. We refer to the ratio of the optimal cost of the robust problem and the optimal cost of the two-stage stochastic problem as the stochasticity gap. We also extend the bound on the stochasticity gap for another class of uncertainty sets referred to as positive. If both the objective coefficients and right-hand side are uncertain, we show that the stochasticity gap can be arbitrarily large even if the uncertainty set and the probability measure are both symmetric. However, we prove that the adaptability gap (ratio of optimal cost of the robust problem and the optimal cost of a two-stage fully adaptable problem) is at most four even if both the objective coefficients and the right-hand side of the constraints are uncertain and belong to a symmetric uncertainty set. The bound holds for the class of positive uncertainty sets as well. Moreover, if the uncertainty set is a hypercube (special case of a symmetric set), the adaptability gap is one under an even more general model of uncertainty where the constraint coefficients are also uncertain.National Science Foundation (U.S.) (NSF Grant DMI-0556106)National Science Foundation (U.S.) (NSF Grant EFRI-0735905

Modeling peptide fragmentation with dynamic Bayesian networks for peptide identification

Motivation: Tandem mass spectrometry (MS/MS) is an indispensable technology for identification of proteins from complex mixtures. Proteins are digested to peptides that are then identified by their fragmentation patterns in the mass spectrometer. Thus, at its core, MS/MS protein identification relies on the relative predictability of peptide fragmentation. Unfortunately, peptide fragmentation is complex and not fully understood, and what is understood is not always exploited by peptide identification algorithms

Gomphrena tomentosa (Griseb.) R.E. Fr. var. ruiz-lealii Subils & Hunz.

Quebrada del Zapallar, QuinespublishedVersio

Green tea extract only affects markers of oxidative status postprandially: lasting antioxidant effect of flavonoid-free diet

Epidemiological studies suggest that foods rich in flavonoids might reduce the risk of cardiovascular disease and cancer. The objective of the present study was to investigate the effect of green tea extract (GTE) used as a food antioxidant on markers of oxidative status after dietary depletion of flavonoids and catechins. The study was designed as a 2×3 weeks blinded human cross-over intervention study (eight smokers, eight non-smokers) with GTE corresponding to a daily intake of 18·6 mg catechins/d. The GTE was incorporated into meat patties and consumed with a strictly controlled diet otherwise low in flavonoids. GTE intervention increased plasma antioxidant capacity from 1·35 to 1·56 (P<0·02) in postprandially collected plasma, most prominently in smokers. The intervention did not significantly affect markers in fasting blood samples, including plasma or haemoglobin protein oxidation, plasma oxidation lagtime, or activities of the erythrocyte superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase. Neither were fasting plasma triacylglycerol, cholesterol, α-tocopherol, retinol, β-carotene, or ascorbic acid affected by intervention. Urinary 8-oxo-deoxyguanosine excretion was also unaffected. Catechins from the extract were excreted into urine with a half-life of less than 2 h in accordance with the short-term effects on plasma antioxidant capacity. Since no long-term effects of GTE were observed, the study essentially served as a fruit and vegetables depletion study. The overall effect of the 10-week period without dietary fruits and vegetables was a decrease in oxidative damage to DNA, blood proteins, and plasma lipids, concomitantly with marked changes in antioxidative defenc

Addressing statistical biases in nucleotide-derived protein databases for proteogenomic search strategies

[Image: see text] Proteogenomics has the potential to advance genome annotation through high quality peptide identifications derived from mass spectrometry experiments, which demonstrate a given gene or isoform is expressed and translated at the protein level. This can advance our understanding of genome function, discovering novel genes and gene structure that have not yet been identified or validated. Because of the high-throughput shotgun nature of most proteomics experiments, it is essential to carefully control for false positives and prevent any potential misannotation. A number of statistical procedures to deal with this are in wide use in proteomics, calculating false discovery rate (FDR) and posterior error probability (PEP) values for groups and individual peptide spectrum matches (PSMs). These methods control for multiple testing and exploit decoy databases to estimate statistical significance. Here, we show that database choice has a major effect on these confidence estimates leading to significant differences in the number of PSMs reported. We note that standard target:decoy approaches using six-frame translations of nucleotide sequences, such as assembled transcriptome data, apparently underestimate the confidence assigned to the PSMs. The source of this error stems from the inflated and unusual nature of the six-frame database, where for every target sequence there exists five “incorrect” targets that are unlikely to code for protein. The attendant FDR and PEP estimates lead to fewer accepted PSMs at fixed thresholds, and we show that this effect is a product of the database and statistical modeling and not the search engine. A variety of approaches to limit database size and remove noncoding target sequences are examined and discussed in terms of the altered statistical estimates generated and PSMs reported. These results are of importance to groups carrying out proteogenomics, aiming to maximize the validation and discovery of gene structure in sequenced genomes, while still controlling for false positives

Engineering Design with Digital Thread

Digital Thread offers the opportunity to use information generated across the product lifecycle to design the next generation of products. In this paper, we introduce a mathematical methodology that establishes the data-driven design and decision problem associated with Digital Thread. Our objectives are twofold: 1) Provide a mathematical definition of Digital Thread in the context of conceptual and preliminary design and establish a methodology for how information along the Digital Thread enters into the design problem as well how design decisions affect the Digital Thread. 2) Develop a data-driven design method that incorporates data from different sources from across the product life cycle. We illustrate aspects of our methodology through an example design of a structural fiber-steered composite component.United States. Air Force. Office of Scientific Research (Grant FA9550-16-1-0108)SUTD-MIT International Design Centre (IDC