Updated benchmarking of variant effect predictors using deep mutational scanning

Abstract The assessment of variant effect predictor (VEP) performance is fraught with biases introduced by benchmarking against clinical observations. In this study, building on our previous work, we use independently generated measurements of protein function from deep mutational scanning (DMS) experiments for 26 human proteins to benchmark 55 different VEPs, while introducing minimal data circularity. Many top‐performing VEPs are unsupervised methods including EVE, DeepSequence and ESM‐1v, a protein language model that ranked first overall. However, the strong performance of recent supervised VEPs, in particular VARITY, shows that developers are taking data circularity and bias issues seriously. We also assess the performance of DMS and unsupervised VEPs for discriminating between known pathogenic and putatively benign missense variants. Our findings are mixed, demonstrating that some DMS datasets perform exceptionally at variant classification, while others are poor. Notably, we observe a striking correlation between VEP agreement with DMS data and performance in identifying clinically relevant variants, strongly supporting the validity of our rankings and the utility of DMS for independent benchmarking

The properties of human disease mutations at protein interfaces

The assembly of proteins into complexes and their interactions with other biomolecules are often vital for their biological function. While it is known that mutations at protein interfaces have a high potential to be damaging and cause human genetic disease, there has been relatively little consideration for how this varies between different types of interfaces. Here we investigate the properties of human pathogenic and putatively benign missense variants at homomeric (isologous and heterologous), heteromeric, DNA, RNA and other ligand interfaces, and at different regions in proteins with respect to those interfaces. We find that different types of interfaces vary greatly in their propensity to be associated with pathogenic mutations, with homomeric heterologous and DNA interfaces being particularly enriched in disease. We also find that residues that do not directly participate in an interface, but are close in three-dimensional space, show a significant disease enrichment. Finally, we observe that mutations at different types of interfaces tend to have distinct property changes when undergoing amino acid substitutions associated with disease, and that this is linked to substantial variability in their identification by computational variant effect predictors

A continuously updated, geospatially rectified database of utility-scale wind turbines in the United States.

Over 60,000 utility-scale wind turbines are installed in the United States as of October, 2019, representing over 97 gigawatts of electric power capacity; US wind turbine installations continue to grow at a rapid pace. Yet, until April 2018, no publicly-available, regularly updated data source existed to describe those turbines and their locations. Under a cooperative research and development agreement, analysts from three organizations collaborated to develop and release the United States Wind Turbine Database (USWTDB) - a publicly available, continuously updated, spatially rectified data source of locations and attributes of utility-scale wind turbines in the United States. Technical specifications and wind facility data, incorporated from five sources, undergo rigorous quality control. The location of each turbine is visually verified using high-resolution aerial imagery. The quarterly-updated data are available in a variety of formats, including an interactive web application, comma-separated values (CSV), shapefile, and application programming interface (API). The data are used widely by academic researchers, engineers and developers from wind energy companies, government agencies, planners, educators, and the general public

Coherent states for continuous spectrum operators with non-normalizable fiducial states

The problem of building coherent states from non-normalizable fiducial states is considered. We propose a way of constructing such coherent states by regularizing the divergence of the fiducial state norm. Then, we successfully apply the formalism to particular cases involving systems with a continuous spectrum: coherent states for the free particle and for the inverted oscillator $(p^2 - x^2)$ are explicitly provided. Similar ideas can be used for other systems having non-normalizable fiducial states.Comment: 17 pages, typos corrected, references adde

OpenFOAM Simulations of Atmospheric-Entry Capsules in the Subsonic Regime

The open-source Computational Fluid Dynamics software OpenFOAM is gaining wider acceptance in industry and academia for incompressible flow simulations. To date, there has been relatively little utilization of OpenFOAM for compressible external aerodynamic applications. The numerous turbulence models available in OpenFOAM makes it an attractive option for evaluating alternate Reynolds-Averaged Navier-Stokes (RANS) turbulent models to assess separated flow on atmospheric entry vehicles in the subsonic regime, where traditional turbulent models show reduced accuracy. This paper presents simulations of an axisymmetric capsule geometry at subsonic conditions using an OpenFOAM compressible flow solver. These results are compared with results from the NASA CFD code OVERFLOW and experimental data. These OpenFOAM simulations serve as a basis to explore OpenFOAMs extended turbulence models on compressible separated flows such as found on entry capsules

Noisy Preprocessing and the Distillation of Private States

We provide a simple security proof for prepare & measure quantum key distribution protocols employing noisy processing and one-way postprocessing of the key. This is achieved by showing that the security of such a protocol is equivalent to that of an associated key distribution protocol in which, instead of the usual maximally-entangled states, a more general {\em private state} is distilled. Besides a more general target state, the usual entanglement distillation tools are employed (in particular, Calderbank-Shor-Steane (CSS)-like codes), with the crucial difference that noisy processing allows some phase errors to be left uncorrected without compromising the privacy of the key.Comment: 4 pages, to appear in Physical Review Letters. Extensively rewritten, with a more detailed discussion of coherent --> iid reductio

The N=1 Supersymmetric Landau Problem and its Supersymmetric Landau Level Projections: the N=1 Supersymmetric Moyal-Voros Superplane

The N=1 supersymmetric invariant Landau problem is constructed and solved. By considering Landau level projections remaining non trivial under N=1 supersymmetry transformations, the algebraic structures of the N=1 supersymmetric covariant non(anti)commutative superplane analogue of the ordinary N=0 noncommutative Moyal-Voros plane are identified