Highlights from the ISCB Student Council Symposium 2013

This report summarizes the scientific content and activities of the annual symposium organized by the Student Council of the International Society for Computational Biology (ISCB), held in conjunction with the Intelligent Systems for Molecular Biology (ISMB) / European Conference on Computational Biology (ECCB) conference in Berlin, Germany, on July 19, 2013

RAPHAEL: recognition, periodicity and insertion assignment of solenoid protein structures.

Abstract Motivation: Repeat proteins form a distinct class of structures where folding is greatly simplified. Several classes have been defined, with solenoid repeats of periodicity between ca. 5 and 40 being the most challenging to detect. Such proteins evolve quickly and their periodicity may be rapidly hidden at sequence level. From a structural point of view, finding solenoids may be complicated by the presence of insertions or multiple domains. To the best of our knowledge, no automated methods are available to characterize solenoid repeats from structure. Results: Here we introduce RAPHAEL, a novel method for the detection of solenoids in protein structures. It reliably solves three problems of increasing difficulty: (1) recognition of solenoid domains, (2) determination of their periodicity and (3) assignment of insertions. RAPHAEL uses a geometric approach mimicking manual classification, producing several numeric parameters that are optimized for maximum performance. The resulting method is very accurate, with 89.5% of solenoid proteins and 97.2% of non-solenoid proteins correctly classified. RAPHAEL periodicities have a Spearman correlation coefficient of 0.877 against the manually established ones. A baseline algorithm for insertion detection in identified solenoids has a Q2 value of 79.8%, suggesting room for further improvement. RAPHAEL finds 1931 highly confident repeat structures not previously annotated as solenoids in the Protein Data Bank records. Availability: The RAPHAEL web server is available with additional data at http://protein.bio.unipd.it/raphael/ Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

APPRIS: selecting functionally important isoforms.

APPRIS (https://appris.bioinfo.cnio.es) is a well-established database housing annotations for protein isoforms for a range of species. APPRIS selects principal isoforms based on protein structure and function features and on cross-species conservation. Most coding genes produce a single main protein isoform and the principal isoforms chosen by the APPRIS database best represent this main cellular isoform. Human genetic data, experimental protein evidence and the distribution of clinical variants all support the relevance of APPRIS principal isoforms. APPRIS annotations and principal isoforms have now been expanded to 10 model organisms. In this paper we highlight the most recent updates to the database. APPRIS annotations have been generated for two new species, cow and chicken, the protein structural information has been augmented with reliable models from the EMBL-EBI AlphaFold database, and we have substantially expanded the confirmatory proteomics evidence available for the human genome. The most significant change in APPRIS has been the implementation of TRIFID functional isoform scores. TRIFID functional scores are assigned to all splice isoforms, and APPRIS uses the TRIFID functional scores and proteomics evidence to determine principal isoforms when core methods cannot.National Human Genome Research Institute of the National Institutes of Health [2 U41 HG007234]; Spanish Ministry of Science, Innovation and Universities [PGC2018-097019-B-I00]; Carlos III Institute of Health-Fondo de Investigacion Sanitaria [PRB3 ´ (IPT17/0019––ISCIII-SGEFI/ERDF, ProteoRed]; ‘la Caixa’ Banking Foundation [HR17-00247]. Funding for open access charge: National Human Genome Research Institute.S

Assessment of building behavior in slow-moving landslide-affected areas through DInSAR data and structural analysis

Slow-moving landslides are a natural hazard which affects wide areas in the world and often are cause of significant damage to structures and infrastructures. Analysis of landslide evolution and of their interaction with existing man-made structures plays a key role in risk prevention and mitigation activities. To this purpose, a considerable interest towards innovative approaches has grown among the scientific community and land management institutions. In this work, Synthetic Aperture Radar data acquired by C-band and X-band sensors, combined with numerical analyses, have been successfully applied as a tool to detect spatial and temporal landslide-induced effects, in terms of deformations and structural behavior of a building affected by ground instability. Such approach has been applied to Moio della Civitella urban settlement (Salerno province, Italy), whose whole territory is interested by several slow-moving landslides. In detail, performance of a masonry building aggregate and the efficacy of restoration works have been investigated through an integrated assessment of displacement time-series pre- and post-repair intervention, and structural analysis performed with numerical code. Historical DInSAR data have permitted firstly the interpretation of building displacement time-series corresponding to pre- and post-works configurations; subsequently, the analysis of interpolated interferometric products has allowed to define gradient maps of vertical and horizontal displacements and to identify part of aggregate which can suffer a greater susceptibility to damage as a consequence of deformation gradients. Finally, the comparison of satellite and numerical data showed a substantial agreement with local failures and damage surveyed, thus confirming the capability of DInSAR technique to investigate building performance where no in situ displacement measurements were available.Research funded by the Campania Region through Regional Law n. 5/2002, year 2008 – Project “La pericolosità delle frane intermittenti in formazioni strutturalmente complesse; analisi comparata dei parametri geologici, mineralogici e geotecnici” (CUP_E64G08000060002) – Scientific manager: prof. Domenico Calcaterra. Part of this work was partially supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO), the State Agency of Research (AEI) and the European Funds for Regional Development (FEDER) under projects TEC2017-85244-C2-1-P and TIN2014-55413-C2-2-P and the Spanish Ministry of Education, Culture and Sport under project PRX17/00439

APPRIS 2017: principal isoforms for multiple gene sets

The APPRIS database (http://appris-tools.org) uses protein structural and functional features and information from cross-species conservation to annotate splice isoforms in protein-coding genes. APPRIS selects a single protein isoform, the ‘principal’ isoform, as the reference for each gene based on these annotations. A single main splice isoform reflects the biological reality for most protein coding genes and APPRIS principal isoforms are the best predictors of these main proteins isoforms. Here, we present the updates to the database, new developments that include the addition of three new species (chimpanzee, Drosophila melangaster and Caenorhabditis elegans), the expansion of APPRIS to cover the RefSeq gene set and the UniProtKB proteome for six species and refinements in the core methods that make up the annotation pipeline. In addition APPRIS now provides a measure of reliability for individual principal isoforms and updates with each release of the GENCODE/Ensembl and RefSeq reference sets. The individual GENCODE/Ensembl, RefSeq and UniProtKB reference gene sets for six organisms have been merged to produce common sets of splice variants.National Institutes of Health [U41 HG007234, 2U41 HG007234]; Spanish Ministry of Economics and Competitiveness [BIO2015-67580-P]; SpanishNational Institute of Bioinformatics (www.inab.org) [INB-ISCIII, PRB2 to J.M.R.]; ProteoRed [IPT13/0001-ISCIII-SGEFI/FEDER to J.V.]; Joint BSC-IRB-CRG Program in Computation Biology and Award Severo Ochoa [SEV 2015-0493 to A.V.]. Funding for open access charge: U.S. Department of Health and Human Services; National Institutes of Health; National Human Genome Research Institute [2U41 HG007234].Peer ReviewedPostprint (published version

Multisource data integration to investigate one century of evolution for the Agnone landslide (Molise, southern Italy)

Landslides are one of the most relevant geohazards worldwide, causing direct and indirect costs and fatalities. Italy is one of the countries most affected by mass movements, and the Molise region, southern Italy, is known to be susceptible to erosional processes and landslides. In January 2003, a landslide in the municipality of Agnone, in the Colle Lapponi-Piano Ovetta (CL-PO) territory, occurred causing substantial damage to both structures and civil infrastructure. To investigate the evolution of the landslide-affected catchment over approximately one century, different data were taken into account: (i) literature information at the beginning of the twentieth century; (ii) historical sets of aerial optical photographs to analyse the geomorphological evolution from 1945 to 2003; (iii) SAR (Synthetic Aperture Radar) data from the ERS1/2, ENVISAT and COSMO-SkyMed satellites to monitor the displacement from 1992 to 2015; (iv) traditional measurements carried out through geological and geomorphological surveys, inclinometers and GPS campaigns to characterize the geological setting of the area; and (v) recent optical photographs of the catchment area to determine the enlargement of the landslide. Using the structure from motion technique, a 3D reconstruction of each set of historical aerial photographs was made to investigate the geomorphological evolution and to trace the boundary of the mass movements. As a result, the combination of multitemporal and multitechnique analysis of the evolution of the CL-PO landslide enabled an assessment of the landslide expansion, which resulted in a maximum length of up to approximately 1500 m. A complete investigation of the past and present deformational sequences of the area was performed to potentially plan further mitigation and prevention strategies to avoid possible reactivations.This work was partially funded by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO); the State Agency of Research (AEI); and the European Funds for Regional Development (FEDER) under projects TEC2017-85244-C2-1-P and TIN2014-55413-C2-2-P and the Spanish Ministry of Education, Culture and Sport under project PRX17/00439

Terminal uridylyltransferases target RNA viruses as part of the innate immune system.

RNA viruses are a major threat to animals and plants. RNA interference (RNAi) and the interferon response provide innate antiviral defense against RNA viruses. Here, we performed a large-scale screen using Caenorhabditis elegans and its natural pathogen the Orsay virus (OrV), and we identified cde-1 as important for antiviral defense. CDE-1 is a homolog of the mammalian TUT4 and TUT7 terminal uridylyltransferases (collectively called TUT4(7)); its catalytic activity is required for its antiviral function. CDE-1 uridylates the 3' end of the OrV RNA genome and promotes its degradation in a manner independent of the RNAi pathway. Likewise, TUT4(7) enzymes uridylate influenza A virus (IAV) mRNAs in mammalian cells. Deletion of TUT4(7) leads to increased IAV mRNA and protein levels. Collectively, these data implicate 3'-terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.CRUK, The Wellcome Trust & ER

Manual de uso de MMAD (Migración de Metadatos y Archivos Digitales)

MMAD (Migración de Metadatos y Archivos Digitales) es un programa desarrollado por la Oficina de Conocimiento Abierto (OCA) y la Prosecretaría de Informática, ambas pertenecientes a la Universidad Nacional de Córdoba (UNC). El programa facilita la migración de metadatos y archivos almacenados en el Módulo Memoria SIGEVA -UNC a su Repositorio Digital Universitario (RDU).Fil: Febre, Alexis. Universidad Nacional de Córdoba. Secretaría de Gestión Institucional. Oficina de Conocimiento Abierto; Argentina.Fil: Cohen Arazi, Tomás. Universidad Nacional de Córdoba. Prosecretaría de Informática; Argentina.Fil: Nardi, Alejandra M. Universidad Nacional de Córdoba. Secretaría de Gestión Institucional. Oficina de Conocimiento Abierto; Argentina.Fil: Di Domenico, Emilio Edgardo. Universidad Nacional de Córdoba. Secretaría de Gestión Institucional. Oficina de Conocimiento Abierto; Argentina.Fil: García, Lucrecia. Universidad Nacional de Córdoba. Secretaría de Gestión Institucional. Oficina de Conocimiento Abierto; Argentina.Fil: García, Lucrecia. Universidad Nacional de Córdoba. Secretaría de Gestión Institucional. Oficina de Conocimiento Abierto; Argentina.Fil: Pizzi, Mario. Universidad Nacional de Córdoba. Secretaría de Gestión Institucional. Oficina de Conocimiento Abierto; Argentina.Fil: Orcellet, Lorena. Universidad Nacional de Córdoba. Prosecretaría de Informática; Argentina.Fil: Scándolo, Carlos Iván. Universidad Nacional de Córdoba. Prosecretaría de Informática; Argentina.Fil: Salvai, Nicolás. Universidad Nacional de Córdoba. Prosecretaría de Informática; Argentina

Informing research priorities for immature sea turtles through expert elicitation

This is the final version. Available from Inter Research via the DOI in this record. Although sea turtles have received substantial focus worldwide, research on the immature life stages is still relatively limited. The latter is of particular importance, given that a large proportion of sea turtle populations comprises immature individuals. We set out to identify knowledge gaps and identify the main barriers hindering research in this field. We analyzed the perceptions of sea turtle experts through an online survey which gathered their opinions on the current state of affairs on immature sea turtle research, including species and regions in need of further study, priority research questions, and barriers that have interfered with the advancement of research. Our gap analysis indicates that studies on immature leatherback Dermochelys coriacea and hawksbill Eretmochelys imbricata turtles are lacking, as are studies on all species based in the Indian, South Pacific, and South Atlantic Oceans. Experts also perceived that studies in population ecology, namely on survivorship and demography, and habitat use/behavior, are needed to advance the state of knowledge on immature sea turtles. Our survey findings indicate the need for more interdisciplinary research, collaborative efforts (e.g. data-sharing, joint field activities), and improved communication among researchers, funding bodies, stakeholders, and decision-makers

METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer

Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N-7-methylguanosine (m(7)G) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of m(7)G tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5'tRNA fragments. 5'tRNA-derived small RNAs steer translation control to favour the synthesis of key regulators of tumour growth suppression, interferon pathway, and immune effectors. Knockdown of Mettl1 in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed m(7)G tRNA methylation in cancer cell translation control and tumour biology