PDBpaint, a visualization webservice to tag protein structures with sequence annotations

SUMMARY: Protein features are often displayed along the linear sequence of amino acids that make up that protein, but in reality these features occupy a position in the folded protein's three-dimensional space. Mapping sequence features to known or predicted protein structures is useful when trying to deduce the function of those features and when evaluating sequence or structural predictions. To facilitate this goal we developed PDBpaint, a simple tool that displays protein sequence features gathered from bioinformatics resources on top of protein structures, which are displayed in an interactive window (using the Jmol Java viewer). PDBpaint can be used either with existing protein structures or with novel structures provided by the user. The current version of PDBpaint allows the visualization of annotations from Pfam, ARD (detection of HEATrepeats), UniProt, TMHMM2.0 and SignalP. Users can also add other annotations manually. Availability and Implementation: PDBpaint is accessible at http://cbdm.mdc-berlin.de/~pdbpaint. Code is available from http://sourceforge.net/projects/pdbpaint. The website was implemented in Perl, with all major browsers supported. CONTACT: [email protected]

A novel approach for protein subcellular location prediction using amino acid exposure

BACKGROUND: Proteins perform their functions in associated cellular locations. Therefore, the study of protein function can be facilitated by predictions of protein location. Protein location can be predicted either from the sequence of a protein alone by identification of targeting peptide sequences and motifs, or by homology to proteins of known location. A third approach, which is complementary, exploits the differences in amino acid composition of proteins associated to different cellular locations, and can be useful if motif and homology information are missing. Here we expand this approach taking into account amino acid composition at different levels of amino acid exposure. RESULTS: Our method has two stages. For stage one, we trained multiple Support Vector Machines (SVMs) to score eukaryotic protein sequences for membership to each of three categories: nuclear, cytoplasmic and extracellular, plus extra category nucleocytoplasmic, accounting for the fact that a large number of proteins shuttles between those two locations. In stage two we use an artificial neural network (ANN) to propose a category from the scores given to the four locations in stage one. The method reaches an accuracy of 68% when using as input 3D-derived values of amino acid exposure. Calibration of the method using predicted values of amino acid exposure allows classifying proteins without 3D-information with an accuracy of 62% and discerning proteins in different locations even if they shared high levels of identity. CONCLUSIONS: In this study we explored the relationship between residue exposure and protein subcellular location. We developed a new algorithm for subcellular location prediction that uses residue exposure signatures. Our algorithm uses a novel approach to address the multiclass classification problem. The algorithm is implemented as web server 'NYCE' and can be accessed at http://cbdm.mdc-berlin.de/~amer/nyce

High pCO 2 levels affect metabolic rate, but not feeding behavior and fitness, of farmed giant mussel Choromytilus chorus

Indexación: Scopus.Acknowledgements. We thank Luisa Saavedra and Araceli Rodriguez-Romero for their help in the field and during laboratory activities. We also acknowledge Laura Ramajo for help with AT estimations. Emily Giles Neill provided valuable comments that greatly improved the manuscript. Special thanks are due to the reviewers and the editor for very constructive comments on the manuscript. This study was supported by the Millennium Nucleus Center for the Study of Multiple drivers on Marine Socio-Ecological Systems (MUSELS) funded by MINECON NC120086, PIA CONICYT ACT-172037 and FONDECYT grant nos. 1140938 and 1140092 to N.A.L. and M.A.L.Mar Ecol Prog Ser 454: 65−74 Findlay HS, Wood HL, Kendall MA, Spicer JI, Twitchett RJ, Widdicombe S (2009) Calcification, a physiological pro-cess to be considered in the context of the whole organ-ism. Biogeosciences 6: 2267−2284 Fitzer SC, Zhu W, Tanner KE, Phoenix VR, Kamenos NA, Cusack M (2015) Ocean acidification alters the material properties of Mytilus edulis shells. J R Soc Interface 12: 214−227 Freitas R, De Marchi L, Bastos M, Moreira A and others (2017) Effects of seawater acidification and salinity alter-ations on metabolic, osmoregulation and oxidative stress markers in Mytilus galloprovincialis. Ecol Indic 79: 54−62 Gattuso JP, Magnan A, Billé R, Cheung WWL and others (2015) Contrasting futures for ocean and society from dif-ferent anthropogenic CO2 emissions scenarios. Science 349: aac4722 Gazeau F, Urbini L, Cox TE, Alliouane S, Gattuso JP (2015) Comparison of the alkalinity and calcium anomaly tech-niques to estimate rates of net calcification. Mar Ecol Prog Ser 527: 1−12 Gray MW, Langdon CJ, Waldbusser GG, Hales B, Kramer S (2017) Mechanistic understanding of ocean acidification impacts on larval feeding physiology and energy budg-ets of the mussel Mytilus californianus. Mar Ecol Prog Ser 563: 81−94 Griffiths CL, Griffiths RJ (1987) Animal energetics, Vol 2: Bivalvia through Reptilia. In: Pandian TJ, Vernberg FJ (eds) Bivalvia. Academic Press, New York, NY, p 1−88 Harvey BP, Dwynn-Jones D, Moore PJ (2013) Meta-analysis reveals complex marine biological responses to the inter-active effects of ocean acidification and warming. Ecol Evol 3: 1016−1030 Hiebenthal C, Philipp EER, Eisenhauer A, Wahl M (2013) Effects of seawater pCO2 and temperature on shell growth, shell stability, condition and cellular stress of western Baltic Sea Mytilus edulis (L.) and Arctica is - landica (L.). Mar Biol 160: 2073−2087 Ibarrola I, Arambalza U, Navarro JM, Urrutia MB, Navarro E (2012) Allometric relationships in feeding and diges-tion in the Chilean mytilids Mytilus chilensis (Hupé), Choromytilus chorus (Molina) and Aulacomya ater (Mo - lina): a comparative study. J Exp Mar Biol Ecol 426-427: 18−27 Lagos NA, Benítez S, Duarte C, Lardies MA and others (2016) Effects of temperature and ocean acidification on shell characteristics of Argopecten purpuratus: implica-tions for scallop aquaculture in an upwelling-influenced area. Aquacult Environ Interact 8: 357−370 Lardies MA, Arias MB, Poupin MJ, Manríquez PH and oth-ers (2014) Differential response to ocean acidification in physiological traits of Concholepas concholepas popula-tions. J Sea Res 90: 127−134 Lardies MA, Benítez S, Osores S, Vargas CA, Duarte C, Lohrmann KB, Lagos NA (2017) Physiological and histo - pathological impacts of increased carbon dioxide and temperature on the scallops Argopecten purpuratus cultured under upwelling influences in northern Chile. Aquaculture 479: 455−466 Lemasson AJ, Fletcher S, Hall-Spencer JM, Knights AM (2017) Linking the biological impacts of ocean acidifica-tion on oysters to changes in ecosystem services: a review. J Exp Mar Biol Ecol 492: 49−62 Mackenzie CL, Ormondroyd GA, Curling SF, Ball RJ, Whitely NM, Malham SK (2014) Ocean warming, more than acidification, reduces shell strength in a commercial shellfish species during food limitation. PLOS ONE 9: e86764 McElhany P (2017) CO2 sensitivity experiments are not suf-ficient to show an effect of ocean acidification. ICES J Mar Sci 74: 926−928 Mehrbach C, Culberson CH, Hawley JE, Pytkowicz RM (1973) Measurement of the apparent dissociation con-stants of carbonic acid in seawater at atmospheric pres-sure. Limnol Oceanogr 18: 897−907 Melzner F, Thomsen J, Koeve W, Oschlies A and others (2013) Future ocean acidification will be amplified by hypoxia in coastal habitats. Mar Biol 160: 1875−1888 Michaelidis B, Ouzounis C, Paleras A, Pörtner HO (2005) Effects of long-term moderate hypercapnia on acid−base balance and growth rate in marine mussels Mytilus gal-loprovincialis. Mar Ecol Prog Ser 293: 109−118 Miller AW, Reynolds AC, Sobrino C, Riedel GF (2009) Shell-fish face uncertain future in high CO2 world: influence of acidification on oyster larvae calcification and growth in estuaries. PLOS ONE 4: e5661 Navarro JM (1988) The effects of salinity on the physio - logical ecology of Choromytilus chorus (Molina, 1782) (Bivalvia: Mytilidae). J Exp Mar Biol Ecol 122: 19−33 Navarro JM, Torres R, Acuña K, Duarte C and others (2013) Impact of medium-term exposure to elevated pCO2 lev-els on the physiological energetics of the mussel Mytilus chilensis. Chemosphere 90: 1242−1248 Navarro JM, Duarte C, Manríquez PH, Lardies MA and oth-ers (2016) Ocean warming and elevated carbon dioxide: multiple stressor impacts on juvenile mussels from south-ern Chile. ICES J Mar Sci 73: 764−771 Nienhuis S, Palmer AR, Harley CD (2010) Elevated CO2 affects shell dissolution rate but not calcification rate in a marine snail. Proc R Soc B 277: 2553−2558 Orr JC, Fabry VJ, Aumont O, Bopp L and others (2005) Anthropogenic ocean acidification over the twenty-first century and its impact on calcifying organisms. Nature 437: 681−686 Osores SJ, Lagos NA, San Martin V, Manríquez PH and others (2017) Plasticity and inter-population variability in physiological and life-history traits of the mussel Mytilus chilensis: a reciprocal transplant experiment. J Exp Mar Biol Ecol 490: 1−12 Palmer AR (1982) Growth in marine gastropods: a non-destructive technique for independently measuring shell and body weight. Malacologia 23: 63−73 Parker LM, Ross PM, O’Connor WA, Borysko L, Raftos DA, Pörtner HO (2012) Adult exposure influences offspring response to ocean acidification in oysters. Glob Change Biol 18: 82−92 Pierrot D, Lewis E, Wallace DWR (2006) MS Excel program developed for CO2 system calculations. ORNL/CDIAC-105a. Carbon Dioxide Information Analysis Center, Oak Ridge National Laboratory, US Department of Energy, Oak Ridge, TN Ramajo L, Marba N, Prado L, Peron S and others (2016) Bio-mineralization changes with food supply confer juvenile scallops (Argopecten purpuratus) resistance to ocean acidification. Glob Change Biol 22: 2025−2037 Range P, Chícharo MA, Ben-Hamadou R, Piló D and others (2014) Impacts of CO2-induced seawater acidification on coastal Mediterranean bivalves and interactions with other climatic stressors. Reg Environ Change 14(Suppl 1): 19−30 Sabine C, Feely RA, Gruber N, Key RM and others (2004) The oceanic sink of anthropogenic CO2. Science 305: 367–371 SERNAPESCA (Servicio Nacional de Pesca y Acuicultura) (2014) Anuarios estadísticos del Servicio Nacional de Pesca y Acuicultura. www.sernapesca.cl Solórzano L (1969) Determination of ammonia in natural waters by the phenolhypochlorite method. Limnol Oce - anogr 14: 799−801 Thomsen J, Melzner F (2010) Moderate seawater acidifica-tion does not elicit long-term metabolic depression in the blue mussel Mytilus edulis. Mar Biol 157: 2667−2676 Thomsen J, Casties I, Pansch C, Körtzinger A, Melzner F (2013) Food availability outweighs ocean acidification effects in juvenile Mytilus edulis: laboratory and field experiments. Glob Change Biol 19: 1017−1027 Thomsen J, Stapp LS, Haynert K, Schade H, Danelli M, Lannig G, Melzner F (2017) Naturally acidified habitat selects for ocean acidification-tolerant mussels. Sci Adv 3: e1602411 Toro B, Navarro JM, Palma-Fleming H (2003) Relationship between bioenergetics responses and organic pollutants in the giant mussel, Choromytilus chorus (Mollusca: Mytilidae). Aquat Toxicol 63: 257−269 Torres R, Pantoja S, Harada N, González HE, Daneri G, Frangopulos M, Fukasawa M (2011) Air-sea CO2 fluxes along the coast of Chile: from CO2 outgassing in central northern upwelling waters to CO2 uptake in southern Patagonian fjords. J Geophys Res 116: C09006 Torres R, Manriquez PH, Duarte C, Navarro JM, Lagos NA, Vargas CA, Lardies MA (2013) Evaluation of a semi - automatic system for long-term seawater carbonate chemistry manipulation. Rev Chil Hist Nat 86: 443−451 Vargas CA, Aguilera V, Martín V, Manríquez P and others (2015) CO2-driven ocean acidification disrupts the filter feeding behavior in Chilean gastropod and bivalve spe-cies from different geographic localities. Estuaries Coasts 38: 1163−1177 Vargas CA, Lagos NA, Lardies MA, Duarte C and others (2017) Species-specific responses to ocean acidification should account for local adaptation and adaptive plasti-city. Nature Ecol Evol 1: 0084 Vargas CA, Cuevas LA, Silva N, Gonzalez HE, Pol-Holz D, Narvaez DA (2018) Influence of glacier melting and river discharges on the nutrient distribution and DIC recycling in the southern Chilean Patagonia. J Geophys Res Bio-geosci 123: 256−270 Velasco LA, Navarro JM (2003) Energetic balance of infau-nal (Mulinia edulis King, 1831) and epifaunal (Mytilus chilensis Hupé, 1854) bivalves in response to wide varia-tions in concentration and quality of seston. J Exp Mar Biol Ecol 296: 79−92 Vihtakari M, Hendriks IE, Holding J, Renaud PE, Duarte CM, Havenhand JN (2013) Effects of ocean acidification and warming on sperm activity and early life stages of the Mediterranean mussel (Mytilus galloprovincialis). Water 5: 1890−1915 Wang Y, Li L, Hu M, Lu W (2015) Physiological energetic of the thick shell mussel Mytilus coruscus exposed to sea-water acidification and thermal stress. Sci Total Environ 514: 261−272 White MM, McCorkle DC, Mullineaux LS, Cohen AL (2013)Benthic habitats such as intertidal areas, sandy or rocky shores, upwelling zones, and estuaries are characterized by variable environmental conditions. This high variability of environmental stressors such as temperature, salinity, and pH/pCO 2 levels have been shown to impose restrictions on organismal performance. The giant mussel Choromytilus chorus forms intertidal and subtidal mussel beds in estuarine zones associated with fjords occurring in southern Chile and is an important aquacultural resource in Patagonia. In this study, we estimated the sensitivity of physiological traits and energy balance of C. chorus juveniles exposed to 3 pCO 2 treatments (500, 750, and 1200 μatm) for 30 d. Results showed that in acidified, high pCO 2 conditions, C. chorus juveniles had increased metabolic rates; however, other physiological traits (clearance and ingestion rates, ammonia excretion, absorption efficiency, growth rate, biomass production, net calcification, and dissolution rates) were not affected. These results suggest that when subjected to acidification, the adaptive response of C. chorus triggers tradeoffs among physiological traits that favor sustained feeding and growth in order to combat increased metabolic stress. As has been reported for other marine organisms, chronic exposure to variable pH/pCO 2 in their native habitats, such as estuarine zones, could explain the differential acclimatization capacity of giant mussels to cope with the increase in pCO 2 . Additionally, the fact that the mussels did not suffer from mortality indicates that increased pCO 2 levels may have chronic, but not lethal, effects on this species under these experimental conditions. © The authors 2017.https://www.int-res.com/abstracts/aei/v10/p267-278

Evolution and function of CAG/polyglutamine repeats in protein-protein interaction networks

Expanded runs of consecutive trinucleotide CAG repeats encoding polyglutamine (polyQ) stretches are observed in the genes of a large number of patients with different genetic diseases such as Huntington's and several Ataxias. Protein aggregation, which is a key feature of most of these diseases, is thought to be triggered by these expanded polyQ sequences in disease-related proteins. However, polyQ tracts are a normal feature of many human proteins, suggesting that they have an important cellular function. To clarify the potential function of polyQ repeats in biological systems, we systematically analyzed available information stored in sequence and protein interaction databases. By integrating genomic, phylogenetic, protein interaction network and functional information, we obtained evidence that polyQ tracts in proteins stabilize protein interactions. This happens most likely through structural changes whereby the polyQ sequence extends a neighboring coiled-coil region to facilitate its interaction with a coiled-coil region in another protein. Alteration of this important biological function due to polyQ expansion results in gain of abnormal interactions, leading to pathological effects like protein aggregation. Our analyses suggest that research on polyQ proteins should shift focus from expanded polyQ proteins into the characterization of the influence of the wild-type polyQ on protein interactions

mBISON: Finding miRNA target over-representation in gene lists from ChIP-sequencing data

BACKGROUND: Over-representation of predicted miRNA targets in sets of genes regulated by a given transcription factor (e.g. as defined by ChIP-sequencing experiments) helps to identify biologically relevant miRNA targets and is useful to get insight into post-transcriptional regulation. FINDINGS: To facilitate the application of this approach we have created the mBISON web-application. mBISON calculates the significance of over-representation of miRNA targets in a given non-ranked gene set. The gene set can be specified either by a list of genes or by one or more ChIP-seq datasets followed by a user-defined peak-gene association procedure. mBISON is based on predictions from TargetScan and uses a randomization step to calculate False-Discovery-Rates for each miRNA, including a correction for gene set specific properties such as 3'UTR length. The tool can be accessed from the following web-resource: http://cbdm.mdc-berlin.de/~mgebhardt/cgi-bin/mbison/home . CONCLUSION: mBISON is a web-application that helps to extract functional information about miRNAs from gene lists, which is in contrast to comparable applications easy to use by everyone and can be applied on ChIP-seq data directly

The Rural Digital Divide in the Face of the COVID-19 Pandemic in Europe-Recommendations from a Scoping Review

The COVID-19 pandemic has revealed the digital vulnerability of many citizens of the rural world. This article identifies and analyzes the proposals made by academic literature to overcome the digital divide in the European rural world for the five-year period 2016-2020. A scoping review has been carried out according to the PRISMA methodology in the two dimensions of the digital divide: access and connectivity, and use and exploitation. Online databases were used to identify scientific articles from which, after screening, 28 key documents were selected. The results update Salemink systematic review of articles published between 1991 and 2014 on digital and rural development in Western countries and it also intends to go beyond by extracting recommendations. A variety of political, social, educational, technical and economic issues has been exposed, with a common emphasis on the empowerment of rural populations. The findings provide actionable evidence and proposals to facilitate decision-making in current policy information to overcome rural digital divide. From them, seven recommendations that could have a wide and rapid impact to minimize the effects of the COVID-19 pandemic linked to the rural digital divide are synthesized. Three lines of action in the medium term are also proposed: the evaluation of national and regional public policies; the consideration of digital inclusion as a potential instrument to reduce rural depopulation; and the training in advanced digital skills to improve the social communication processes, considered key to promote empowerment and entrepreneurship

Comparing climatic suitability and niche distances to explain populations responses to extreme climatic events

Habitat suitability calculated from Species Distribution Models (SDMs) has been used to assess population performance, but empirical studies have provided weak or inconclusive support to this approach. Novel approaches measuring population distances to niche centroid and margin in environmental space have been recently proposed to explain population performance, particularly when populations experience exceptional environmental conditions that may place them outside of the species niche. Here, we use data of co-occurring species’ decay, gathered after an extreme drought event occurring in the SE of the Iberian Peninsula which highly affected rich semiarid shrubland communities, to compare the relationship between population decay (mortality and remaining green canopy) and (1) distances between populations’ location and species niche margin and centroid in the environmental space, and (2) climatic suitability estimated from frequently used SDMs (here MaxEnt) considering both the extreme climatic episode and the average reference climatic period before this. We found that both SDMs-derived suitability and distances to species niche properly predict populations performance when considering the reference climatic period; but climatic suitability failed to predict performance considering the extreme climate period. In addition, while distance to niche margins accurately predict both mortality and remaining green canopy responses, centroid distances failed to explain mortality, suggesting that indexes containing information about the position to niche margin (inside or outside) are better to predict binary responses. We conclude that the location of populations in the environmental space is consistent with performance responses to extreme drought. Niche distances appear to be a more efficient approach than the use of climate suitability indices derived from more frequently used SDMs to explain population performance when dealing with environmental conditions that are located outside the species environmental niche. The use of this alternative metrics may be particularly useful when designing conservation measures to mitigate impacts of shifting environmental conditions

Alkemio: association of chemicals with biomedical topics by text and data mining

The PubMed(R) database of biomedical citations allows the retrieval of scientific articles studying the function of chemicals in biology and medicine. Mining millions of available citations to search reported associations between chemicals and topics of interest would require substantial human time. We have implemented the Alkemio text mining web tool and SOAP web service to help in this task. The tool uses biomedical articles discussing chemicals (including drugs), predicts their relatedness to the query topic with a naïve Bayesian classifier and ranks all chemicals by P-values computed from random simulations. Benchmarks on seven human pathways showed good retrieval performance (areas under the receiver operating characteristic curves ranged from 73.6 to 94.5%). Comparison with existing tools to retrieve chemicals associated to eight diseases showed the higher precision and recall of Alkemio when considering the top 10 candidate chemicals. Alkemio is a high performing web tool ranking chemicals for any biomedical topics and it is free to non-commercial users. Availability: http://cbdm.mdc-berlin.de/∼medlineranker/cms/alkemio

Update of the G2D tool for prioritization of gene candidates to inherited diseases

G2D (genes to diseases) is a web resource for prioritizing genes as candidates for inherited diseases. It uses three algorithms based on different prioritization strategies. The input to the server is the genomic region where the user is looking for the disease-causing mutation, plus an additional piece of information depending on the algorithm used. This information can either be the disease phenotype (described as an online Mendelian inheritance in man (OMIM) identifier), one or several genes known or suspected to be associated with the disease (defined by their Entrez Gene identifiers), or a second genomic region that has been linked as well to the disease. In the latter case, the tool uses known or predicted interactions between genes in the two regions extracted from the STRING database. The output in every case is an ordered list of candidate genes in the region of interest. For the first two of the three methods, the candidate genes are first retrieved through sequence homology search, then scored accordingly to the corresponding method. This means that some of them will correspond to well-known characterized genes, and others will overlap with predicted genes, thus providing a wider analysis. G2D is publicly available at http://www.ogic.ca/projects/g2d_2

Outer membrane pore protein prediction in mycobacteria using genomic comparison

Proteins responsible for outer membrane transport across the unique membrane structure of Mycobacterium spp. are attractive drug targets in the treatment of human diseases caused by the mycobacterial pathogens, M. tuberculosis, M. bovis, M. leprae and M. ulcerans. In contrast to E. coli, relatively few outer membrane proteins (OMPs) have been identified in Mycobacterium spp., largely due to the difficulties in isolating mycobacterial membrane proteins and our incomplete understanding of secretion mechanisms and cell wall structure in these organisms. To further expand our knowledge of these elusive proteins in Mycobacterium, we have improved upon our previous method of OMP prediction in mycobacteria by taking advantage of genomic data from seven mycobacteria species. Our improved algorithm suggests 4333 sequences as putative OMPs in these seven species with varying degrees of confidence. The most virulent pathogenic mycobacterial species are slightly enriched in these selected sequences. We present examples of predicted OMPs involved in horizontal transfer and paralogy expansion. Analysis of local secondary structure content allowed identifying small domains predicted to perform as OMPs; some examples show their involvement in events of tandem duplication and domain rearrangements. We discuss the taxonomic distribution of these discovered families and architectures, often specific to mycobacteria or the wider taxonomic class of Actinobacteria. Our results suggest that OMP functionality in mycobacteria is richer than expected and provide a resource to guide future research of these understudied proteins