Use of accounting concepts to study research: return on investment in XSEDE, a US cyberinfrastructure service.

This paper uses accounting concepts-particularly the concept of Return on Investment (ROI)-to reveal the quantitative value of scientific research pertaining to a major US cyberinfrastructure project (XSEDE-the eXtreme Science and Engineering Discovery Environment). XSEDE provides operational and support services for advanced information technology systems, cloud systems, and supercomputers supporting non-classified US research, with an average budget for XSEDE of US$20M+ per year over the period studied (2014-2021). To assess the financial effectiveness of these services, we calculated a proxy for ROI, and converted quantitative measures of XSEDE service delivery into financial values using costs for service from the US marketplace. We calculated two estimates of ROI: a Conservative Estimate, functioning as a lower bound and using publicly available data for a lower valuation of XSEDE services; and a Best Available Estimate, functioning as a more accurate estimate, but using some unpublished valuation data. Using the largest dataset assembled for analysis of ROI for a cyberinfrastructure project, we found a Conservative Estimate of ROI of 1.87, and a Best Available Estimate of ROI of 3.24. Through accounting methods, we show that XSEDE services offer excellent value to the US government, that the services offered uniquely by XSEDE (that is, not otherwise available for purchase) were the most valuable to the facilitation of US research activities, and that accounting-based concepts hold great value for understanding the mechanisms of scientific research generally.

Improving access to geodetic imaging crustal deformation data using GeoGateway.

GeoGateway (http://geo-gateway.org) is a web-based interface for analysis and modeling of geodetic imaging data and to support response to related disasters. Geodetic imaging data product currently supported by GeoGateway include Global Navigation Satellite System (GNSS) daily position time series and derived velocities and displacements and airborne Interferometric Synthetic Aperture Radar (InSAR) from NASA's UAVSAR platform. GeoGateway allows users to layer data products in a web map interface and extract information from various tools. Extracted products can be downloaded for further analysis. GeoGateway includes overlays of California fault traces, seismicity from user selected search parameters, and user supplied map files. GeoGateway also provides earthquake nowcasts and hazard maps as well as products created for related response to natural disasters. A user guide is present in the GeoGateway interface. The GeoGateway development team is also growing the user base through workshops, webinars, and video tutorials. GeoGateway is used in the classroom and for research by experts and non-experts including by students.

Clustering Analysis Methods for GNSS Observations: A Data-Driven Approach to Identifying California's Major Faults.

We present a data-driven approach to clustering or grouping Global Navigation Satellite System (GNSS) stations according to observed velocities, displacements or other selected characteristics. Clustering GNSS stations provides useful scientific information, and is a necessary initial step in other analysis, such as detecting aseismic transient signals (Granat et al., 2013, https://doi.org/10.1785/0220130039). Desired features of the data can be selected for clustering, including some subset of displacement or velocity components, uncertainty estimates, station location, and other relevant information. Based on those selections, the clustering procedure autonomously groups the GNSS stations according to a selected clustering method. We have implemented this approach as a Python application, allowing us to draw upon the full range of open source clustering methods available in Python's scikit-learn package (Pedregosa et al., 2011, https://doi.org/10.5555/1953048.2078195). The application returns the stations labeled by group as a table and color coded KML file and is designed to work with the GNSS information available from GeoGateway (Donnellan et al., 2021, https://doi.org/10.1007/s12145-020-00561-7; Heflin et al., 2020, https://doi.org/10.1029/2019ea000644) but is easily extensible. We demonstrate the methodology on California and western Nevada. The results show partitions that follow faults or geologic boundaries, including for recent large earthquakes and post-seismic motion. The San Andreas fault system is most prominent, reflecting Pacific-North American plate boundary motion. Deformation reflected as class boundaries is distributed north and south of the central California creeping section. For most models a cluster boundary connects the southernmost San Andreas fault with the Eastern California Shear Zone (ECSZ) rather than continuing through the San Gorgonio Pass.

Buried Aseismic Slip and Off-Fault Deformation on the Southernmost San Andreas Fault Triggered by the 2010 El Mayor Cucapah Earthquake Revealed by UAVSAR.

We use UAVSAR interferograms to characterize fault slip, triggered by the Mw 7.2 El Mayor-Cucapah earthquake on the 1 San Andreas Fault in the Coachella Valley providing comprehensive maps of short-term geodetic surface deformation that complement in situ measurements. Creepmeters and geological mapping of fault offsets on Durmid Hill recorded 4 and 8 mm of average triggered slip respectively on the fault, in contrast to radar views that reveal significant off-fault dextral deformation averaging 20 mm. Unlike slip in previous triggered slip events on the southernmost San Andreas fault, dextral shear in 2010 is not confined to transpressional hills in the Coachella valley. Edge detection and gradient estimation applied to the 50-m-sampled interferogram data identify the location (to 20 m) and local strike (to <4°) of secondary surface ruptures. Transverse curve fitting applied to these local detections provides local estimates of the radar-projected dextral slip and a parameter indicating the transverse width of the slip, which we equate with the depth of subsurface shear. These estimates are partially validated by fault-transverse interferogram profiles generated using the GeoGateway UAVSAR tool, and appear consistent for radar-projected slip greater than about 5 mm. An unexpected finding is that creep and triggered slip on the San Andreas fault terminate in the shallow subsurface below a surface shear zone that resists the simple expression of aseismic fault slip. We introduce the notion of a surface locking depth above which fault slip is manifest as distributed shear, and evaluate its depth as 6-27 m.

TopPIC Gateway: A Web Gateway for Top-Down Mass Spectrometry Data Interpretation.

Top-down mass spectrometry-based proteomics has become the method of choice for identifying and quantifying intact proteoforms in biological samples. We present a web-based gateway for TopPIC suite, a widely used software suite consisting of four software tools for top-down mass spectrometry data interpretation: TopFD, TopPIC, TopMG, and TopDiff. The gateway enables the community to use heterogeneous collection of computing resources that includes high performance computing clusters at Indiana University and virtual clusters on XSEDE's Jetstream Cloud resource for top-down mass spectral data analysis using TopPIC suite. The gateway will be a useful resource for proteomics researchers and students who have limited access to high-performance computing resources or who are not familiar with interacting with server-side supercomputers.

Building a Science Gateway For Processing and Modeling Sequencing Data Via Apache Airavata.

The amount of DNA sequencing data has been exponentially growing during the past decade due to advances in sequencing technology. Processing and modeling large amounts of sequencing data can be computationally intractable for desktop computing platforms. High performance computing (HPC) resources offer advantages in terms of computing power, and can be a general solution to these problems. Using HPCs directly for computational needs requires skilled users who know their way around HPCs and acquiring such skills take time. Science gateways acts as the middle layer between users and HPCs, providing users with the resources to accomplish compute-intensive tasks without requiring specialized expertise. We developed a web-based computing platform for genome biologists by customizing the PHP Gateway for Airavata (PGA) framework that accesses publicly accessible HPC resources via Apache Airavata. This web computing platform takes advantage of the Extreme Science and Engineering Discovery Environment (XSEDE) which provides the resources for gateway development, including access to CPU, GPU, and storage resources. We used this platform to develop a gateway for the dREG algorithm, an online computing tool for finding functional regions in mammalian genomes using nascent RNA sequencing data. The dREG gateway provides its users a free, powerful and user-friendly GPU computing resource based on XSEDE, circumventing the need of specialized knowledge about installation, configuration, and execution on an HPC for biologists. The dREG gateway is available at: https://dREG.dnasequence.org/.

Sharpening peripheral dose gradient via beam number enhancement from patient head tilt for stereotactic brain radiosurgery.

Sharp dose fall-off is the hallmark of brain radiosurgery for the purpose of delivering high dose radiation to the target while minimizing peripheral dose to regional normal brain tissue. In this study, a technique was developed to enhance the peripheral dose gradient by magnifying the total number of beams focused toward each isocenter through pre-programmed patient head tilting. This technique was tested in clinical settings on a dedicated brain radiosurgical system (GKPFX, Gamma Knife Perfexion, Elekta Oncology) by comparing dosimetry as well as delivery efficiency for 20 radiosurgical cases previously treated with the system. The 3-fold beam number enhancement (BNE) treatment plans were found to produce nearly identical target volume coverage (absolute value < 0.5%, P > 0.2) and dose conformity (BNE CI = 1.41 ± 0.22 versus 1.41 ± 0.11, P > 0.99) as the original treatment plans. The total beam-on time for the 3-fold BNE treatment plans were also found to be comparable (<0.5 min or 2%) with those of the original treatment plans for all the cases. However, BNE treatment plans significantly improved the mean gradient index (BNE GI = 2.94 ± 0.27 versus original GI = 2.98 ± 0.28 P < 0.0001) and low-level isodose volumes, e.g. 20-50% prescribed isodose volumes, by 1.7%-3.9% (P < 0.03). With further 4-5-fold increase in the total number of beams, the absolute gradient index can decrease by as much as -0.5 in absolute value or -20% for a treatment. In conclusion, BNE via patient head tilt has been demonstrated to be a clinically suitable and efficient technique for physically sharpening the peripheral dose gradient for brain radiosurgery.

Potential for a large earthquake near Los Angeles inferred from the 2014 La Habra earthquake.

Tectonic motion across the Los Angeles region is distributed across an intricate network of strike-slip and thrust faults that will be released in destructive earthquakes similar to or larger than the 1933 M6.4 Long Beach and 1994 M6.7 Northridge events. Here we show that Los Angeles regional thrust, strike-slip, and oblique faults are connected and move concurrently with measurable surface deformation, even in moderate magnitude earthquakes, as part of a fault system that accommodates north-south shortening and westerly tectonic escape of northern Los Angeles. The 28 March 2014 M5.1 La Habra earthquake occurred on a northeast striking, northwest dipping left-lateral oblique thrust fault northeast of Los Angeles. We present crustal deformation observation spanning the earthquake showing that concurrent deformation occurred on several structures in the shallow crust. The seismic moment of the earthquake is 82% of the total geodetic moment released. Slip within the unconsolidated upper sedimentary layer may reflect shallow release of accumulated strain on still-locked deeper structures. A future M6.1-6.3 earthquake would account for the accumulated strain. Such an event could occur on any one or several of these faults, which may not have been identified by geologic surface mapping.

Advances in cheminformatics methodologies and infrastructure to support the data mining of large, heterogeneous chemical datasets.

In recent years, there has been an explosion in the availability of publicly accessible chemical information, including chemical structures of small molecules, structure-derived properties and associated biological activities in a variety of assays. These data sources present us with a significant opportunity to develop and apply computational tools to extract and understand the underlying structure-activity relationships. Furthermore, by integrating chemical data sources with biological information (protein structure, gene expression and so on), we can attempt to build up a holistic view of the effects of small molecules in biological systems. Equally important is the ability for non-experts to access and utilize state of the art cheminformatics method and models. In this review we present recent developments in cheminformatics methodologies and infrastructure that provide a robust, distributed approach to mining large and complex chemical datasets. In the area of methodology development, we highlight recent work on characterizing structure-activity landscapes, Quantitative Structure Activity Relationship (QSAR) model domain applicability and the use of chemical similarity in text mining. In the area of infrastructure, we discuss a distributed web services framework that allows easy deployment and uniform access to computational (statistics, cheminformatics and computational chemistry) methods, data and models. We also discuss the development of PubChem derived databases and highlight techniques that allow us to scale the infrastructure to extremely large compound collections, by use of distributed processing on Grids. Given that the above work is applicable to arbitrary types of cheminformatics problems, we also present some case studies related to virtual screening for anti-malarials and predictions of anti-cancer activity.

BioDrugScreen: a computational drug design resource for ranking molecules docked to the human proteome.

BioDrugScreen is a resource for ranking molecules docked against a large number of targets in the human proteome. Nearly 1600 molecules from the freely available NCI diversity set were docked onto 1926 cavities identified on 1589 human targets resulting in >3 million receptor-ligand complexes requiring >200,000 cpu-hours on the TeraGrid. The targets in BioDrugScreen originated from Human Cancer Protein Interaction Network, which we have updated, as well as the Human Druggable Proteome, which we have created for the purpose of this effort. This makes the BioDrugScreen resource highly valuable in drug discovery. The receptor-ligand complexes within the database can be ranked using standard and well-established scoring functions like AutoDock, DockScore, ChemScore, X-Score, GoldScore, DFIRE and PMF. In addition, we have scored the complexes with more intensive GBSA and PBSA approaches requiring an additional 120,000 cpu-hours on the TeraGrid. We constructed a simple interface to enable users to view top-ranking molecules and access purchasing and other information for further experimental exploration.

Web service infrastructure for chemoinformatics.

The vast increase of pertinent information available to drug discovery scientists means that there is a strong demand for tools and techniques for organizing and intelligently mining this information for manageable human consumption. At Indiana University, we have developed an infrastructure of chemoinformatics Web services that simplifies the access to this information and the computational techniques that can be applied to it. In this paper, we describe this infrastructure, give some examples of its use, and then discuss our plans to use it as a platform for chemoinformatics application development in the future.

Building messaging substrates for Web and Grid applications.

Grid application frameworks have increasingly aligned themselves with the developments in Web services. Web services are currently the most popular infrastructure based on service-oriented architecture (SOA) paradigm. There are three core areas within the SOA framework: (i) a set of capabilities that are remotely accessible, (ii) communications using messages and (iii) metadata pertaining to the aforementioned capabilities. In this paper, we focus on issues related to the messaging substrate hosting these services; we base these discussions on the NARADABROKERING system. We outline strategies to leverage capabilities available within the substrate without the need to make any changes to the service implementations themselves. We also identify the set of services needed to build Grids of Grids. Finally, we discuss another technology, HPSEARCH, which facilitates the administration of the substrate and the deployment of applications via a scripting interface. These issues have direct relevance to scientific Grid applications, which need to go beyond remote procedure calls in client-server interactions to support integrated distributed applications that couple databases, high performance computing codes and visualization codes.