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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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Information-incorporated gene network construction with FDR control

Abstract Motivation Large-scale gene expression studies allow gene network construction to uncover associations among genes. To study direct associations among genes, partial correlation-based networks are preferred over marginal correlations. However, FDR control for partial correlation-based network construction is not well-studied. In addition, currently available partial correlation-based methods cannot take existing biological knowledge to help network construction while controlling FDR. Results In this paper, we propose a method called Partial Correlation Graph with Information Incorporation (PCGII). PCGII estimates partial correlations between each pair of genes by regularized node-wise regression that can incorporate prior knowledge while controlling the effects of all other genes. It handles high-dimensional data where the number of genes can be much larger than the sample size and controls FDR at the same time. We compare PCGII with several existing approaches through extensive simulation studies and demonstrate that PCGII has better FDR control and higher power. We apply PCGII to a plant gene expression dataset where it recovers confirmed regulatory relationships and a hub node, as well as several direct associations that shed light on potential functional relationships in the system. We also introduce a method to supplement observed data with a pseudogene to apply PCGII when no prior information is available, which also allows checking FDR control and power for real data analysis. Availability and implementation R package is freely available for download at https://cran.r-project.org/package=PCGII.

59 BASIC BIOLOGICAL SCIENCES↗

Target–decoy false discovery rate estimation using Crema

Assigning statistical confidence estimates to discoveries produced by a tandem mass spectrometry proteomics experiment is critical to enabling principled interpretation of the results and assessing the cost/benefit ratio of experimental follow-up. The most common technique for computing such estimates is to use target-decoy competition (TDC), in which observed spectra are searched against a database of real (target) peptides and a database of shuffled or reversed (decoy) peptides. TDC procedures for estimating the false discovery rate (FDR) at a given score threshold have been developed for application at the level of spectra, peptides, or proteins. Although these techniques are relatively straightforward to implement, it is common in the literature to skip over the implementation details or even to make mistakes in how the TDC procedures are applied in practice. Here we present Crema, an open-source Python tool that implements several TDC methods of spectrum-, peptide- and protein-level FDR estimation. Crema is compatible with a variety of existing database search tools and provides a straightforward way to obtain robust FDR estimates.

59 BASIC BIOLOGICAL SCIENCES↗

Chemoproteogenomic stratification of the missense variant cysteinome

Abstract Cancer genomes are rife with genetic variants; one key outcome of this variation is widespread gain-of-cysteine mutations. These acquired cysteines can be both driver mutations and sites targeted by precision therapies. However, despite their ubiquity, nearly all acquired cysteines remain unidentified via chemoproteomics; identification is a critical step to enable functional analysis, including assessment of potential druggability and susceptibility to oxidation. Here, we pair cysteine chemoproteomics—a technique that enables proteome-wide pinpointing of functional, redox sensitive, and potentially druggable residues—with genomics to reveal the hidden landscape of cysteine genetic variation. Our chemoproteogenomics platform integrates chemoproteomic, whole exome, and RNA-seq data, with a customized two-stage false discovery rate (FDR) error controlled proteomic search, which is further enhanced with a user-friendly FragPipe interface. Chemoproteogenomics analysis reveals that cysteine acquisition is a ubiquitous feature of both healthy and cancer genomes that is further elevated in the context of decreased DNA repair. Reference cysteines proximal to missense variants are also found to be pervasive, supporting heretofore untapped opportunities for variant-specific chemical probe development campaigns. As chemoproteogenomics is further distinguished by sample-matched combinatorial variant databases and is compatible with redox proteomics and small molecule screening, we expect widespread utility in guiding proteoform-specific biology and therapeutic discovery.

Desai, Heta (ORCID:0000000343621707)↗

Navier-Stokes Analysis of the Flowfield Characteristics of an Ice Contaminated Aircraft Wing

An analytical study was performed as part of the NASA Lewis support of a National Transportation Safety Board (NTSB) aircraft accident investigation. The study was focused on the performance degradation associated with ice contamination on the wing of a commercial turbo-prop-powered aircraft. Based upon the results of an earlier numerical study conducted by the authors, a prominent ridged-ice formation on the subject aircraft wing was selected for detailed flow analysis using 2-dimensional (2-D), as well as, 3-dimensional (3-D) Navier-Stokes computations. This configuration was selected because it caused the largest lift decrease and drag increase among all the ice shapes investigated in the earlier study. A grid sensitivity test was performed to find out the influence of grid spacing on the lift, drag, and associated angle-of-attack for the maximum lift (C(sub lmax)). This study showed that grid resolution is important and a sensitivity analysis is an essential element of the process in order to assure that the final solution is independent of the grid. The 2-D results suggested that a severe stability and control difficulty could have occurred at a slightly higher angle-of-attack (AOA) than the one recorded by the Flight Data Recorder (FDR). This stability and control problem was thought to have resulted from a decreased differential lift on the wings with respect to the normal loading for the configuration. The analysis also indicated that this stability and control problem could have occurred whether or not natural ice shedding took place. Numerical results using an assumed 3-D ice shape showed an increase of the angle at which this phenomena occurred of about 4 degrees. As it occurred with the 2-D case, the trailing edge separation was observed but started only when the AOA was very close to the angle at which the maximum lift occurred.

Chung, J.↗

Characterizing the Joint Effect of Diverse Test-Statistic Correlation Structures and Effect Size on False Discovery Rates in a Multiple-Comparison Study of Many Outcome Measures

In their 2009 Annals of Statistics paper, Gavrilov, Benjamini, and Sarkar report the results of a simulation assessing the robustness of their adaptive step-down procedure (GBS) for controlling the false discovery rate (FDR) when normally distributed test statistics are serially correlated. In this study we extend the investigation to the case of multiple comparisons involving correlated non-central t-statistics, in particular when several treatments or time periods are being compared to a control in a repeated-measures design with many dependent outcome measures. In addition, we consider several dependence structures other than serial correlation and illustrate how the FDR depends on the interaction between effect size and the type of correlation structure as indexed by Foerstner s distance metric from an identity. The relationship between the correlation matrix R of the original dependent variables and R~, the correlation matrix of associated t-statistics is also studied. In general R~ depends not only on R, but also on sample size and the signed effect sizes for the multiple comparisons.

Feiveson, Alan H.↗

Spread spectrum time domain reflectometry (SSTDR) and frequency domain reflectometry (FDR) cable inspection using machine learning

Cables are initially qualified for nuclear power plant use for 40 years. As plants extend their operating license to 60 and 80 years, justification for continued cable use must shift to a condition-based approach since it is cost prohibitive to completely replace cables that are likely still capable of performing their design function. The Pacific Northwest National Laboratory (PNNL) Accelerated and Real Time Experimental Nodal Analysis (ARENA) cable motor test bed was used to test the response of a commercial spread spectrum time domain reflectometry (SSTDR) system, a laboratory instrument software-controlled SSTDR, and a vector network analyzer-based frequency domain reflectometry (FDR) system to various cable anomalies. The three instrument systems were able to interrogate cables over a range of frequency bandwidths that can be helpful for human data analysis. Data were subjected to supervised and unsupervised machine learning (ML) analyses to distinguish normal undamaged cable responses from anomalous cable responses. Both supervised and unsupervised ML approaches produced encouraging results with an undamaged/anomalous prediction accuracy from 0.69% to 0.87%. Recommendations for further development and field implementation include increased and more balanced sample sets particularly including more training data.

SSTDR, FDR, Reflectometry, Machine Learning, ARENA↗

Reconstruction of the 1994 Pittsburgh Airplane Accident Using a Computer Simulation

On September 8, 1994, a Boeing 737-300 passenger airplane was on a downwind approach to the Pittsburgh International Airport at an altitude of 5000 feet above ground level (6000 feet MSL). While in a shallow left turn onto a downwind approach heading, the airplane crossed into the vortex trail of a Boeing 727 flying in the same approach pattern about 4 miles ahead. The B-737 airplane rolled and turned sharply to the left, exited the vortex wake and plunged into the ground. Weather was not a factor in the accident. The airplane was equipped with a 11+ channel digital Flight Data Recorder (FDR) and a multiple channel Cockpit Voice Recorder (CVR). Both recorders were recovered from the crash site and provided excellent data for the development of an accident scenario. Radar tracking of the two airplanes as well as the indicated air speed (IAS) perturbations clearly visible on the B-737 FDR recordings indicate that the upset was apparently initiated by the airplane's crossing into the wake of the B-727 flying ahead in the same traffic pattern. A 6 degree-of-freedom simulation program for the B-737 airplane using MATLAB and SIMULINK was constructed. The simulation was initialized at the stabilized flight conditions of the airplane about 13 seconds prior to its entry into the vortex trail of the B-727 airplane. By assuming a certain combination of control inputs, it was possible to produce a simulated motion that closely matched that recorded on the FDR.

Parks, Edwin K.↗

PROACTIVE Focus Area 4: Structured Decision Metrics Analysis (Final Report)

A structured decision metrics analysis was developed as one of the tasks under PROACTIVE’s Focus Area 4 (FA4) and used structured decision metrics for processes, items, and facilities (PIF) to determine the efficacy of an M&V system in meeting treaty goals and technical objectives. The method starts with the functional decomposition of a “treaty” with the M&V system overlaid on it. A Functional Decomposition Rubric (FDR) for each PIF is used to determine a score ranging from 0 (weak) to 4 (strong) for assurance, security, and burden. The individual scores are combined to provide an overall Verification System Score (VSS) which assesses the overall verification system’s suitability given goals; scores for each step of the process are also given. The outcome of the evaluation is to identify needs or modifications to the enterprise model, verification system, or proposed testbed capabilities. VeriScore was used to evaluate FA4’s Spiral 0 exercise; those results are included in this report. The VeriScore and FDR framework can also be used in a non-treaty environment, as any goal/objective/method structure will work, thus expanding its applicability beyond traditional arms control structures.

99 GENERAL AND MISCELLANEOUS↗

An Experimental and Numerical Study of Icing Effects on the Performance and Controllability of a Twin Engine Aircraft

In September 1997 the National Transportation Safety Board (NTSB) requested assistance from the NASA Lewis Research Center (LeRC) Icing Branch in the investigation of an aircraft accident that was suspected of being caused by ice contamination. In response to the request NASA agreed to perform an experimental and computational study. The main activities that NASA performed were LERC Icing Research Tunnel (IRT) testing to define ice shapes and 2-D Navier-Stokes analysis to determine the performance degradation that those ice shapes would have caused. An IRT test was conducted in January 1998. Most conditions for the test were based upon raw and derived data from the Flight Data Recorder (FDR) recovered from the accident and upon the current understanding of the Meteorological conditions near the accident. Using a two-dimensional Navier-Stokes code, the flow field and resultant lift and drag were calculated for the wing section with various ice shapes accreted in the IRT test. Before the final calculations could be performed extensive examinations of geometry smoothing and turbulence were conducted. The most significant finding of this effort is that several of the five-minute ice accretions generated in the IRT were found by the Navier-Stokes analysis to produce severe lift and drag degradation. The information generated by this study suggests a possible scenario for the kind of control upset recorded in the accident. Secondary findings were that the ice shapes accreted in the IRT were mostly limited to the protected pneumatic boot region of the wing and that during testing, activation of the pneumatic boots cleared most of the ice.

Reehorst, A.↗