The Natural Products Atlas 2.0 : a database of microbially-derived natural products

Within the natural products field there is an increasing emphasis on the study of compounds from microbial sources. This has been fuelled by interest in the central role that microorganisms play in mediating both interspecies interactions and host-microbe relationships. To support the study of natural products chemistry produced by microorganisms we released the Natural Products Atlas, a database of known microbial natural products structures, in 2019. This paper reports the release of a new version of the database which includes a full RESTful application programming interface (API), a new website framework, and an expanded database that includes 8128 new compounds, bringing the total to 32 552. In addition to these structural and content changes we have added full taxonomic descriptions for all microbial taxa and have added chemical ontology terms from both NP Classifier and ClassyFire. We have also performed manual curation to review all entries with incomplete configurational assignments and have integrated data from external resources, including CyanoMetDB. Finally, we have improved the user experience by updating the Overview dashboard and creating a dashboard for taxonomic origin. The database can be accessed via the new interactive website at https://www.npatlas.org.Peer reviewe

Treatment as prevention effect of direct-acting antivirals on primary hepatitis C virus incidence: Findings from a multinational cohort between 2010 and 2019.

BACKGROUND Broad direct-acting antiviral (DAA) access may reduce hepatitis C virus (HCV) incidence through a "treatment as prevention" (TasP) effect. We assessed changes in primary HCV incidence following DAA access among people living with HIV (PLHIV). METHODS We used pooled individual-level data from six cohorts from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). Follow-up started from the first recorded negative HCV antibody test date and ended at last negative antibody test or estimated infection date. Follow-up was restricted to 2010-2019. We used segmented Poisson regression to model trends across pre-, limited- (i.e., restrictions on access) and broad-DAA access periods. FINDINGS Overall, 45,942 participants had at least one HCV antibody negative result and follow-up between 2010 and 2019. We observed 2042 incident HCV infections over 248,189 person-years (PY). Pooled incidence decreased from 0.91 per 100 PY in 2015 to 0.41 per 100 PY in 2019. Compared to the average pre-DAA period incidence (0.90 per 100 PY), average incidence was similar during the limited-DAA access period (Incidence rate ratio [IRR] = 0.98; 95%CI = 0.87, 1.11), and 52% lower during the broad-DAA access period (IRR = 0.48; 95%CI = 0.42, 0.52). The average annual decline in HCV incidence was 2% in the pre-DAA period; an additional 9% annual decline in incidence was observed during the limited-DAA access period (IRR = 0.91; 95%CI = 0.82, 1.00) and a further 20% decline in the broad-DAA access period (IRR = 0.80, 95%CI = 0.73, 0.89). INTERPRETATION Our findings suggest that broad DAA access has a TasP effect on primary HCV incidence among PLHIV. Based on the initial years of DAA availability, the countries in the InCHEHC collaboration are on track to meet the World Health Organization's 80% HCV incidence reduction target for PLHIV by 2030. FUNDING This study was funded by the Australian Government National Health and Medical Research Council (Grant number GNT1132902)

The Natural Products Atlas : an open access knowledge base for microbial natural products discovery

Despite rapid evolution in the area of microbial natural products chemistry, there is currently no open access database containing all microbially produced natural product structures. Lack of availability of these data is preventing the implementation of new technologies in natural products science. Specifically, development of new computational strategies for compound characterization and identification are being hampered by the lack of a comprehensive database of known compounds against which to compare experimental data. The creation of an open access, community-maintained database of microbial natural product structures would enable the development of new technologies in natural products discovery and improve the interoperability of existing natural products data resources. However, these data are spread unevenly throughout the historical scientific literature, including both journal articles and international patents. These documents have no standard format, are often not digitized as machine readable text, and are not publicly available. Further, none of these documents have associated structure files (e.g., MOL, InChI, or SMILES), instead containing images of structures. This makes extraction and formatting of relevant natural products data a formidable challenge. Using a combination of manual curation and automated data mining approaches we have created a database of microbial natural products (The Natural Products Atlas, www.npatlas.org) that includes 24 594 compounds and contains referenced data for structure, compound names, source organisms, isolation references, total syntheses, and instances of structural reassignment. This database is accompanied by an interactive web portal that permits searching by structure, substructure, and physical properties. The Web site also provides mechanisms for visualizing natural products chemical space and dashboards for displaying author and discovery timeline data. These interactive tools offer a powerful knowledge base for natural products discovery with a central interface for structure and property-based searching and presents new viewpoints on structural diversity in natural products. The Natural Products Atlas has been developed under FAIR principles (Findable, Accessible, Interoperable, and Reusable) and is integrated with other emerging natural product databases, including the Minimum Information About a Biosynthetic Gene Cluster (MIBiG) repository, and the Global Natural Products Social Molecular Networking (GNPS) platform. It is designed as a community-supported resource to provide a central repository for known natural product structures from microorganisms and is the first comprehensive, open access resource of this type. It is expected that the Natural Products Atlas will enable the development of new natural products discovery modalities and accelerate the process of structural characterization for complex natural products libraries

Hybrid cosmic ray measurements using the IceAct telescopes in coincidence with the IceCube and IceTop detectors

IceAct is a proposed surface array of compact (50 cm diameter) and cost-effective Imaging Air Cherenkov Telescopes installed at the site of the IceCube Neutrino Observatory at the geographic South Pole. Since January 2019, two IceAct telescope demonstrators, featuring 61 silicon photomultiplier (SiPM) pixels have been taking data in the center of the IceTop surface array during the austral winter. We present the first analysis of hybrid cosmic ray events detected by the IceAct imaging air-Cherenkov telescopes in coincidence with the IceCube Neutrino Observatory, including the IceTop surface array and the IceCube in-ice array. By featuring an energy threshold of about 10 TeV and a wide field-of-view, the IceAct telescopes show promising capabilities of improving current cosmic ray composition studies: measuring the Cherenkov light emissions in the atmosphere adds new information about the shower development not accessible with the current detectors, enabling significantly better primary particle type discrimination on a statistical basis. The hybrid measurement also allows for detailed feasibility studies of detector cross-calibration and of cosmic ray veto capabilities for neutrino analyses. We present the performance of the telescopes, the results from the analysis of two years of data, and an outlook of a hybrid simulation for a future telescope array