bluuebunny/crossref_metadata_2025 huggingface dataset:
Trophic analysis of the fish community in the Ciénega Churince, Cuatro Ciénegas, Coahuila
Authors: Hernández Ariana , Espinosa-Pérez Hector S , Souza Valeria
Published: January 2018

The fish community in the Churince system includes endemic, native and introduced species. Fish diets were analysed in order to evaluate the tropho-dynamics of the community. Nine sampling campaigns were carried out between February 2011 and May 2014, and 556 specimens of nine fish species were collected. Stomach contents were analysed using the Index of Relative Importance (IRI) and the Index of Absolute Importance (RIa). Similar groups were defined for the trophic chain using the average linkage method. Feeding strategies were stenophagic in only the species Herichthys minckleyi and euryphagic in the other eight species. The main food categories found in the stomach contents of the fish community were insects, crustaceans, gastropods, plants and teleosts. Four functional groups were defined for the trophic chain, with no top consumer fish species. Despite this, the fish were observed to be regulators, mainly of invertebrates. The chain reaction in the control of food was thus greater from the top to the bottom.
Assessing plant pathogen infection rates in natural soils using R
Authors: Rall Björn C , Latz Ellen
Published: January 2018

The potential of soils to naturally suppress inherent plant pathogens is an important ecosystem function. Usually, pathogen infection assays are used for estimating the suppressive potential of soils. In natural soils, however, co-occurring pathogens might simultaneously infect plants complicating the estimation of a focal pathogen's infection rate as a measure of soil suppressiveness. Here, we present a method in R correcting for these unwanted effects by developing a two pathogen mono-molecular infection model. We fit the two pathogen mono-molecular infection model to data by using an integrative approach combining a numerical simulation of the model with an iterative maximum likelihood fit. We show that in presence of co-occurring pathogens uncorrected data critically under- respectively overestimate soil suppressiveness measures. In contrast, our new approach enables to precisely estimate soil suppressiveness measures such as plant infection rate and plant resistance time. Our method allows a correction of measured infection parameters that is necessary in case different pathogens are present. We propose our method to be particularly useful for exploring soil suppressiveness of natural soils from different sites (e.g., in biodiversity experiments).
ExMarine: An experimental field mesocosm system to study multiple-stressor impacts on rock pool biodiversity
Authors: Macher Jan Niklas
Published: January 2018

Biodiversity loss due to increasing anthropogenic activities is one of the biggest threats to humanity. Understanding the impacts of multiple-stressors on ecosystems and biodiversity is therefore an urgent task. Shore ecosystems are especially valuable, as they harbour a high biodiversity and provide important ecosystems services. Until now, experimental approaches addressing multiple-stressor impacts on these ecosystems have been rare and mostly run with a limited number of replicates and under non-natural conditions. Here, an experimental field mesocosm system that allows studying multiple-stressor impacts on rock pool biodiversity is proposed. The ExMarine mesocosm system is composed of 64 experimental rock pool mesocosms in a fully randomised block design, which allows studying multiple-stressor impacts under highly standardised conditions. Water is taken directly from the sea, allowing biota to immigrate and emigrate freely. Water flow into the mesocosms can be regulated and it is possible to simulate disturbance through waves during high tide. The system can help to understand the impacts of multiple stressors on biodiversity, to monitor ecosystem health and to plan measures preventing the further loss of biodiversity.
Notes on some Glass Frogs (Anura: Centrolenidae) from Western Ecuador: Taxonomy, natural history and conservation status, with the description of a new species
Authors: Cisneros-Heredia Diego F , McDiarmid Roy W.
Published: January 2018

Ecuador has the biggest number of amphibian species per unit of area in the world (425 species in 283,560 km2). In the last decade, conservative estimates indicate that at least 26 species of Ecuadorian amphibians have declined or gone extinct. The reasons for this crisis are not clear but have been related to habitat destruction, climate change, and/or diseases, such as chytridiomycosis. The Río Palenque Science Center (RPSC) was among the last remnants of tropical rainforest in the western lowlands of Ecuador. Twenty years ago, investigations done by R. McDiarmid, Ken Miyata and others lead to the discovery of an amazing herpetofauna, including several undescribed species. However, the expansion of the agricultural frontier and transformation of the forest remnants into oil palm and banana plantations destroyed this site. Among the species identified from RPSC were five species of glass frogs (family Centrolenidae): Centrolene prosoblepon, Cochranella spinosa, Hyalinobatrachium fleischmanni, Hyalinobatrachium sp. (cf. valerioi), and an undescribed species of the genus Centrolene. This research analyzed the morphological characters and natural history of the five glass frogs of RPSC in order to describe the new species of Centrolene from RPSC, which seems to be critically endangered, if not extinct. The new species is characterized by a combination of the following characters: 1) distinctive coloration in life with dark flecks and yellow dorsolateral stripes on a green dorsum; 2) parietal peritoneum white, covering about ½ of the venter, pericardium white, liver and stomach without guanophores, large intestine with guanophores; 3) presence of exposed prepollical spines; 4) humeral spines in males; 5) unique glandular nuptial pad between fingers I and II; and 5) reddish iris.
Did an Ebola outbreak influence the 2014 U.S. federal elections? (Hint: Only if you ignore autocorrelation)
Authors: Tiokhin Leonid , Hruschka Daniel
Published: January 2018

In a recent paper, Beall, Hofer, and Schaller (2016) use observational time series data to test the hypothesis that the 2014 Ebola outbreak influenced the 2014 U.S. Federal Elections. They find substantial associations between online search volume for Ebola and people’s tendency to vote Republican, an effect observed primarily in states with norms favoring Republican candidates. However, the analyses do not deal with the well-known problem of temporal autocorrelation in time series. We show that all variables analyzed exhibit extremely high levels of temporal autocorrelation (i.e. similarity in data-point values across time). After appropriately removing first-order autocorrelation, the observed relationships are attenuated and non-significant. This suggests that either no real associations exist, or that existing data are insufficiently powered to test the proposed hypotheses. We conclude by highlighting other pitfalls of observational data analysis, and draw attention to analytical strategies developed in related disciplines for avoiding these errors.
Software Citation Principles
Authors: Smith Arfon M , Katz Daniel S , Niemeyer Kyle E ,   FORCE11 Software Citation Working Group
Published: January 2018

Software is a critical part of modern research and yet there is little support across the scholarly ecosystem for its acknowledgement and citation. Inspired by the activities of the FORCE11 working group focussed on data citation, this document summarizes the recommendations of the FORCE11 Software Citation Working Group and its activities between June 2015 and April 2016. Based on a review of existing community practices, the goal of the working group was to produce a consolidated set of citation principles that may encourage broad adoption of a consistent policy for software citation across disciplines and venues. Our work is presented here as a set of software citation principles, a discussion of the motivations for developing the principles, reviews of existing community practice, and a discussion of the requirements these principles would place upon different stakeholders. Working examples and possible technical solutions for how these principles can be implemented will be discussed in a separate paper.
Software Citation Principles
Authors: Smith Arfon M , Katz Daniel S , Niemeyer Kyle E ,   FORCE11 Software Citation Working Group
Published: January 2018

Software is a critical part of modern research and yet there is little support across the scholarly ecosystem for its acknowledgement and citation. Inspired by the activities of the FORCE11 working group focused on data citation, this document summarizes the recommendations of the FORCE11 Software Citation Working Group and its activities between June 2015 and April 2016. Based on a review of existing community practices, the goal of the working group was to produce a consolidated set of citation principles that may encourage broad adoption of a consistent policy for software citation across disciplines and venues. Our work is presented here as a set of software citation principles, a discussion of the motivations for developing the principles, reviews of existing community practice, and a discussion of the requirements these principles would place upon different stakeholders. Working examples and possible technical solutions for how these principles can be implemented will be discussed in a separate paper.
A GPU-based high performance computing infrastructure for specialized NGS analyses
Authors: Manconi Andrea , Moscatelli Marco , Gnocchi Matteo , Armano Giuliano , Milanesi Luciano
Published: January 2018

Motivation

Recent advances in genome sequencing and biological data analysis technologies used in bioinformatics have led to a fast and continuous increase in biological data. The difficulty of managing the huge amounts of data currently available to researchers and the need to have results within a reasonable time have led to the use of distributed and parallel computing infrastructures for their analysis. Recently, bioinformatics is exploring new approaches based on the use of hardware accelerators as GPUs. From an architectural perspective, GPUs are very different from traditional CPUs. Indeed, the latter are devices composed of few cores with lots of cache memory able to handle a few software threads at a time. Conversely, the former are devices equipped with hundreds of cores able to handle thousands of threads simultaneously, so that a very high level of parallelism can be reached. Use of GPUs over the last years has resulted in significant increases in the performance of certain applications. Despite GPUs are increasingly used in bioinformatics most laboratories do not have access to a GPU cluster or server. In this context, it is very important to provide useful services to use these tools.

Methods

A web-based platform has been implemented with the aim to enable researchers to perform their analysis through dedicated GPU-based computing resources. To this end, a GPU cluster equipped with 16 NVIDIA Tesla k20c cards has been configured. The infrastructure has been built upon the Galaxy technology [1]. Galaxy is an open web-based scientific workflow system for data intensive biomedical research accessible to researchers that do not have programming experience. Let us recall that Galaxy provides a public server, but it does not provide support to GPU-computing. By default, Galaxy is designed to run jobs on local systems. However, it can also be configured to run jobs on a cluster. The front-end Galaxy application runs on a single server, but tools are run on cluster nodes instead. To this end, Galaxy supports different distributed resource managers with the aim to enable different clusters. For the specific case, in our opinion SLURM [2] represents the most suitable workload manager to manage and control jobs. SLURM is a highly configurable workload and resource manager and it is currently used on six of the ten most powerful computers in the world including the Piz Daint, utilizing over 5000 NVIDIA Tesla K20 GPUs.

Results

GPU-based tools [3] devised by our group for quality control of NGS data have been used to test the infrastructure. Initially, this activity required to make changes to the tools with the aim to optimize the parallelization on the cluster according to the adopted workload manager. Successively, the tools have been converted into web-based services accessible through the Galaxy portal.

Abstract truncated at 3,000 characters - the full version is available in the pdf file.
Effect of body condition on follicle transcriptome in estrous goats
Authors: Wang Zi-Yu , Meng Chun-Hua , Ding Xiao-Lin , Zhang Guo-Min , Wang Feng
Published: January 2018

Body condition or obesity has profound effects on estrus, follicle development, endocrine and conception in both livestock and human beings. To identify potential genes and pathways associated with follicle development in goats of different body condition scores (BCSs), the global gene expression levels of 2.0-3.5 mm follicles from 24 Yangtze River Delta white goats were analyzed by ribonucleic acid sequencing (RNA-Seq). A total of 2,019 differentially expressed genes (DEGs) were identified in obese goats compared with the control, with 381 up-regulated and 1,638 down-regulated. A total of 309 DEGs were associated with reproduction in top-15-cluster-frequency Gene Ontology (GO) terms, and they accounted for 47.3% of all DEGs in biological process classification (653). Using Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, several pathways relevant to reproduction and metabolism were enriched, such as cytokine-cytokine receptor interaction, steroid hormone biosynthesis, etc. Based on the results of GO analysis and KEGG analysis, eight DEGs related to reproduction and metabolism were selected for quantitative real-time polymerase chain reaction (qRT-PCR) assays. The results showed that the expression level of these genes exhibited similar trends to the expression pattern of RNA-Seq. In addition, no significant difference was found in the intrafollicular estradiol (E2) concentration between the obese group and the control. The concentrations of progesterone (P4) and leptin were lower, and a higher E2/P4 ratio was found in the obese group. In summary, the establishment of goat follicle transcriptome would provide a useful reference for the molecular mechanism of follicle development. The combined analysis of DEGs, enriched pathways and follicular fluid composition revealed that P4 and leptin might be potential biomarkers of follicle development in goats.
A review of population-based management of Southern mountain caribou in BC
Authors: Boutin Stan , Merrill Evelyn
Published: January 2018

The decline in Mountain caribou in BC over the past decades has resulted in extensive basic and applied research to guide caribou management by understanding the proximate and ultimate causes of the decline. At the top of the list is high predation rates brought about by human alteration of habitat and the subsequent alteration of predator-prey dynamics. We reviewed population-based management experiments undertaken in BC to recover caribou populations. These included primary prey (moose) reduction, lethal predator control, maternal penning, translocations, and supplemental feeding. Moose reduction by liberalized harvests has led to wolf population reduction and stabilization of treated caribou herds. Translocations have had limited success and finding source populations for future attempts will be a challenge. Maternity pens are producing promising results but their efficacy is strongest in relatively small populations and best results appear to occur when combined with predator control in areas surrounding the pens. Predator control experiments have just begun and results are forthcoming. Overall, no single population-based management tool has increased caribou populations. It is recommended that multiple levers need to be applied in combination on an experimental basis going forward.
The mass, metabolism and length explanation can simultaneously calculate an animal’s mass and metabolic rate from its characteristic length
Authors: Frasier Charles C
Published: January 2018

It is shown that the mass, metabolism and length explanation (MMLE) can simultaneously compute an animal’s body mass and BMR given its characteristic length using data for humans.

MMLE was advanced in 1984 to explain the relationship between metabolic rate and body mass for birds and mammals. It was modernized in 2015 by explicitly treating dynamic similarity of mammals’ skeletal musculature and revising the treatment of BMR. Using two primary equations MMLE deterministically computes the absolute value of Basal Metabolic Rate (BMR) and body mass for individual animals as functions of an individual animal’s characteristic length and sturdiness factor. The characteristic length is a measureable skeletal length associated with an animal’s means of propulsion. The sturdiness factor expresses how sturdy or gracile an animal is. Eight other parameters occur in the equations that vary little among animals in the same phylogenetic group. A mass and length data set with 575 entries from the orders Rodentia, Chiroptera, Artiodactyla, Carnivora, Perissodactyla and Proboscidea and a BMR and mass data set with 436 entries from the orders Rodentia, Chiroptera, Artiodactyla and Carnivora were used to estimate values for the parameters occurring in the equations. With the estimated values MMLE can exactly compute every BMR and mass datum from the BMR and mass data set. Furthermore, MMLE can exactly compute every body mass datum from the mass and length data set. Since there is not a data set that simultaneously reports body mass, BMR and characteristic length for individual animals from the mammal orders that were analyzed it could not be determined whether or not MMLE could simultaneously compute both an animal’s BMR and body mass given its characteristic length.

There are large data sets that report body mass, BMR and height for humans. A human’s characteristic length can be estimated from height. In this paper human data categorized by sex, age and body mass index (BMI) are used to show that MMLE can indeed simultaneously compute a human’s body mass and BMR given his or her characteristic length.

The MMLE body mass equation is modified to explicitly address body fat because it appears that humans are fatter than other running/walking placental mammals. Differences in body fat seem to account for body mass and BMR sexual dimorphism among humans. The impact on BMR of the large and metabolically expensive human brain is addressed. Also mitochondria capability decline with age is addressed.
HiPPO and PANDA: two bioinformatics tools to support analysis of high-dimensional mass cytometry data
Authors: Pirrò Stefano , Cerquone Perpetuini Andrea , Marinkovic Milica , Perfetto Livia , Petrilli Lucia Lisa , Rosina Marco , Spada Filomena , Castagnoli Luisa , Cesareni Gianni
Published: January 2018

Biological processes are modulated by the interaction of different cell types and their study requires technologies able to analyse single cells in heterogeneous populations.

High-dimensional mass cytometry enables the single cell analysis of more than 40 parameters. Several computational approaches have been proposed to reduce the multidimensionality of the datasets produced by this technology (i.e. SPADE and viSNE for clustering and visualization).

We have developed two new bioinformatics tools that help overcoming some of the limitations of the available toolboxes by defining quasi homogeneous cell populations (HIPPO) and by matching their expression profiles with that of cell populations described in the literature.

HiPPO uses a supervised quantitation approach to discretize the expression distribution curves generated for each marker monitored in the experiments. Cells in the continuous, multidimensional dataset are converted into a bi-dimensional matrix where row and columns are events (cells) and markers, respectively.

In order to characterize cell populations, HiPPO queries PANDA, a manually-curated database which stores expression profiles for selected markers of primary cells. The comparison and PANDA discrete expression profiles with those identified by PANDA in the populations under study, allow to monitor cell type abundance.

Moreover, given a set of experiments in different conditions, HiPPO can evaluate the variation of protein expression levels, for any identified population. This is performed by the use of Kolmogorov-Smirnov non-parametric test, evaluating empirical distribution differences of two samples. The analysis is conducted interactively, through a user-friendly web application.

HiPPO ability to identify populations and rapidity of execution have been evaluated and compared with the popular SPADE and viSNE tools. For benchmarking we have used a published dataset of healthy human bone marrow biopsies analysed with the CyTOF platform by simultaneously measuring 34 parameters in single cells [1]. As use case, we focused on 5 cell populations (Mature/Naïve T-helper cells, Mature/Naïve T-cytotoxic cells, B cells). The abundance of cell populations identified by HiPPO is highly-comparable to SPADE and viSNE analysis conducted by the authors. On the other hand HIPPO is 2,15X faster in completing the analysis.

Hippo is a resource that can be easily used to analyze high-throughput multi-dimensional data. The synergy with PANDA represent a substantial improvement in the analysis pipeline and helps overcoming some of the shortcomings of other tools.

HiPPO is freely available at http://160.80.35.248/hippo, PANDA at http://160.80.35.248/panda
How patch size and refuge availability change interaction strength and population dynamics: a combined individual- and population-based modeling experiment
Authors: Li Yuanheng , Brose Ulrich , Meyer Katrin , Rall Björn C
Published: January 2018

Knowledge on how functional responses (a measurement of feeding interaction strength) are affected by patch size and habitat complexity (represented by refuge availability) is crucial for understanding food-web stability and subsequently biodiversity. Due to their laborious character, it is almost impossible to carry out systematic empirical experiments on functional responses across wide gradients of patch sizes and refuge availabilities. Here we overcame this issue by using an individual-based model (IBM) to simulate feeding experiments. The model is based on empirically measured traits such as body size dependent speed and capture success. We simulated these experiments in patches ranging from size of petri dishes to natural patches in the field. Moreover, we varied the refuge availability within the patch independently of patch size, allowing for an independent analyses of both variables. The maximum feeding rate (the maximum number of prey a predator can consume in a given time frame) is independent of patch size and refuge availability, as it is the physiological upper limit of feeding rates. Moreover, the results of these simulations revealed that a type III functional response, which is known to have a stabilizing effect on population dynamics, fits the data best. The half saturation density (the prey density where a predator consumes half of its maximum feeding rate) increased with refuge availability but was only marginally influenced by patch size. Subsequently, we investigated how patch size and refuge availability influence stability and coexistence of predator-prey systems. Following common practice, we used an allometric scaled Rosenzweig-MacArthur predator-prey model based on results from our in silico IBM experiments. The results suggested that densities of both populations are nearly constant across the range of patch sizes simulated, resulting from the constant interaction strength across the patch sizes. However, constant densities with decreasing patch sizes mean a decrease of absolute number of individuals, consequently leading to extinction of predators in smallest patches. Moreover, increasing refuge availabilities also allowed predator and prey to coexist by decreased interaction strengths. Our results underline the need for protecting large patches with high habitat complexity to sustain biodiversity.
Monitoring natural and rural ecosystems using the NDVI anomaly: an application to the Umbria Region
Authors: Massei Gianluca , Rocchi Lucia , Paolotti Luisa , Boggia Antonio
Published: January 2018

The aim of this work is to present a semi-automatic system that, through the use of a plurality of software tools, is able to obtain data from the satellite MODIS / Terra Vegetation Indices 16-Day L3 250m SIN Global Grid (MOD13Q1), to process them and to provide results (in terms of DEVNDVI) almost in real time. The model is applied to the Umbrian territory, for analyzing the dynamics of the vegetation. The applications proposed are two: the former is on the whole regional vegetation, while the latter considers just one specific agrarian typology, the olive orchards. The analysis of anomalies is possible thanks to a database of data collected since January 1st 2001. The comparison between NDVIi and NDVIaverage (the latter taken from the database) allows to identify areas, and the corresponding habitats, which show significant anomalies. Information obtained from such an analysis can be used for constructing synthetic indicators, representing the response of vegetation to climate variability. These indicators can be very useful to identify suffering areas, within particular habitat or ground coverings, such as vineyard and olive groves for example, or to monitor areas sensitive to climate variability (Sykes,2009)
Loop size optimization: a new mechanism for protein stabilization
Authors: Ruggiero Alessia , Balasco Nicole , Esposito Luciana , Vitagliano Luigi
Published: January 2018

Motivation

One of the fundamental issues in both chemistry and biology is the identification of the structural determinants that dictate protein folding and stability. The decoding of the folding code of protein structures would have a major impact on native structure prediction and on de novo design. This task is particularly difficult to achieve. Unlike synthetic polymers, protein structures combine complexity, fine-tuning and marginal stability. Despite these difficulties, in recent years major progresses have been made. A very recent breakthrough in the field is represented by the discovery of Baker and colleagues that the juxtaposition of basic secondary structure elements (α-helices and β-strands) follows well-defined rules ( Koga et al., 2012 ) . These investigations identified three fundamental rules for the preferences of βℓβ (strand-loop-strand), αℓβ (helix-loop-strand) and βℓα (strand-loop-helix) structural motifs. In particular, it was shown that the chirality of βℓβ and the orientation of βℓα/αℓβ strongly depend on the loop size. In this framework, we evaluated the impact of these rules on protein structures isolated from either (hyper)thermophilic or mesophilic organisms. We used the thioredoxin (Trx) system to experimentally validate the results emerged from the statistical analyses.

Methods

Statistical surveys

Our statistical survey was based on the analyses of different structural databases made of proteins isolated from mesophilic or thermophilic organisms by assuming that the proteins of thermophilic species were on average more stable than those isolated from mesophilic ones. The adherence of these proteins to the rules identified by Baker and coworkers was evaluated.

Experiments

Wild-type E. coli Trx and a series of ad-hoc mutants were expressed and purified. The stability of these proteins was evaluated by CD spectroscopy. The structure of these variants was determined by X-ray crystallography.

Results

The statistical analyses indicate that in proteins isolated from thermophilic organisms better adhere to the Baker rules through the optimization of the size of the loop connecting secondary structure elements ( Balasco et al., 2013 ) . We then experimentally validated this mechanism using the thioredoxin isolated from E.coli (EcTrx), a widely characterized protein that has been used as a model in a large number of investigations ( Esposito et al., 2012 , Ruggiero et al., 2009 ) . Comparative analyses of loop sizes between EcTrx and Trx isolated from hyperthermophiles suggested that the size loop connecting helix 1 (α1) to strand 2 (β2) in EcTrx could be modified to better follow the rules. Chimeric variants were therefore prepared by replacing the loop of EcTrx with the corresponding ones present in the Trx isolated from Sulfolobus solfataricus and S. tokodaii.

Abstract truncated at 3,000 characters - the full version is available in the pdf file
Receptor flexibility in molecular cross-docking
Authors: Sessa Lucia , Di BIasi Luigi , Parisi Rosaura , Concilio Simona , Piotto Stefano
Published: January 2018

Motivation

Molecular docking is an efficient method to predict the conformations adopted by the ligand within the target binding site. Usually, standard docking protocol involves only one structure to represent the receptor, overlooking the changes in the binding pocket geometry induced by ligand binding. In our previous work, we observed that different conformations of the same target show different volume and shape of the internal cavities (Sessa et al., 2016). Different ligands may stabilize different receptor conformations with different internal cavities. Consequently, the crystallographic data represent the adaptation of a protein to a particular ligand. Cross-docking is a validation procedure consisting in docking a series of ligands into different conformation of the same receptor. Since the structures of the same receptor can be rather different, the cross-docking analyses are typically very poor. In these cases the internal cavity of the buried binding pocket does not have space enough to accommodate all ligands and this can radically affect the outcome and alter the cross-docking results. The changes of the cavity volume might explain the failure of traditional docking method and support the hypothesis that a single representative structure for the receptor is not enough. Keeping target proteins flexible during the docking has a high computational cost. To overcome this limit, our docking strategy is to represent receptor flexibility through an inexpensive method that generates a series of target structures. Starting from a known target structure, we used the molecular dynamics (MD) simulations to explore the conformational changes induced by ligand binding and to collect several snapshots of receptor structures to perform the cross-docking studies. To validate the accuracy of our flexible protocol in docking, we used a set of 10 crystallographic conformations of Androgen Receptor with the same target but with a different ligand. We performed two parallel experiments of docking, one with a rigid protein target and one considering flexible receptor structures. In addition, we compared the results for both experiments in the re-docking and in the cross-docking analysis.

Methods

Ten receptor structures complexed with a ligand were extracted from the X-ray structures in the PDB database (Berman et al., 2000). Several conformations for each receptor were selected from the molecular dynamics simulations (MD) at regular time intervals (each 500 ps). The MD simulations were performed with the software YASARA Structure 16.2.14 (Krieger & Vriend, 2014) using AMBER14 as force field. The molecular docking simulations were performed using VINA provided in the YASARA package.

"Abstract truncated at 3,000 characters - the full version is available in the pdf file"
Greater than X kb: A quantitative assessment of preservation conditions on genomic DNA quality, and a proposed standard for genome-quality DNA
Authors: Mulcahy Daniel G. , Macdonald III Kenneth S. , Brady Seán G. , Meyer Christopher , Barker Katharine B. , Coddington Jonathan
Published: January 2018

Advances in biodiversity genomic sequencing will increasingly depend on the availability of DNA samples—and their quantifiable metadata—preserved in large institutional biorepositories that are discoverable to the scientific community. Improvements in sequencing technology constantly provide longer reads, such that longer fragment length, higher molecular weight, and overall “genome-quality” DNA (gDNA) will be desirable. Ideally, biorepositories should publish numerical scale measurements of DNA quality useful to the user community. However, the most widely used technique to evaluate DNA quality, the classic agarose gel, has yet to be quantified. Here we propose a simple and economical method using open source image analysis software to make gDNA gel images quantifiable, and propose percentage of gDNA “greater than X kb” as a standard of comparison, where X is a band from any widely used DNA ladder with desirably large band sizes. We employ two metadata standards (“DNA Threshold” and “Percent above Threshold”) introduced as part of the Global Genome Biodiversity Network (GGBN) Darwin Core extension. We illustrate the method using the traditionally used HindIII ladder and the 9,416 base-pair (bp) band as a standard. We also present data, for two taxa, a vertebrate (fish) and an invertebrate (crab), on how gDNA quality varies with seven tissue preservation methods, time since death, preservation method (i.e. buffers vs. cold temperatures), and storage temperature of various buffers over time. Our results suggest that putting tissue into a buffer prior to freezing may be better than directly into ultra-cold conditions.
Digitising a machine-tractable version of Kamus Dewan with TEI-P5
Authors: Lim Lian Tze , Chiew Ruoh Tau , Tang Enya Kong , Abdul Ghani Rusli , Yusof Naimah
Published: January 2018

Kamus Dewan is the authoritative dictionary for Bahasa Malaysia, containing a wealth of linguistic and cultural information about Bahasa Malaysia. It is currently available in print, as well as a searchable online dictionary. However, the online dictionary lacks advanced search capabilities that target specific fields within each headword and lemma entry. For this information to be targeted and extracted efficiently by computers, the macro- and micro-structures of Kamus Dewan entries need to be first annotated or marked up explicitly. We describe how TEI-P5 guidelines have been applied in this endeavour to make the Kamus Dewan more machine-tractable. We also give some examples of how the machine-tractable data from Kamus Dewan can be used for linguistic research and analysis, as well as for producing other language resources.
Evaluation of the parallel performance of the TRIGRS v2.1 model for rainfall-induced landslides
Authors: Alvioli Massimiliano , Spiga Daniele , Baum Rex L
Published: January 2018

The widespread availability of high resolution digital elevation models (DEM) opens the possibility of applying physically based models of landslide initiation to large areas. With increasing size of the study area and resolution of the DEM, the required computing time for each run of the model increases proportionally to the number of grid cells in the study area. The aim of this work is to present a new parallel implementation of TRIGRS (Alvioli and Baum, 2016), an open-source FORTRAN program (software available for download at http://geomorphology.irpi.cnr.it/tools/trigrs and https://github.com/usgs/landslides-trigrs) designed for modeling the timing and distribution of shallow, rainfall-induced landslides, and to discuss its parallel performance.
Open Source for Water Management: including capabilities of MODFLOW-OWHM in the FREEWAT GIS modelling environment
Authors: Bosi Iacopo , Rossetto Rudy , Cannata Massimiliano , De Filippis Giovanna , Ghetta Matteo
Published: January 2018

FREEWAT is an ongoing GIS environment to serve as pre- and post-processor for running simulations of surface-/groundwater interaction, with the possibility to activate several features accounting for the different water stresses. This paper reports the capability related to address water resource management problems, by activating management tools available in the MODFLOW-OWHM code. The latter is integrated in FREEWAT, which appears as composite plugin of the well-know QGIS software (QGIS, 2016). Therefore, all the necessary pre- and post-process procedures can be run effectively within QGIS, also in conjunction with the several tools for GIS analysis already included in QGIS. It turns out a simple and intuitive user interface to manage the simulation of complex problem in which the mutual interaction among surface waters, groundwaters and anthropic water demand/supply terms can be handled. The development phase of such tools is already at an advanced stage, while next work will be focused on producing real-world applications to serve as tutorial for interest Users.
YUCCA auxin biosynthetic genes are required for Arabidopsis shade avoidance
Authors: Müller-Moulé Patricia , Nozue Kazunari , Pytlak Melissa L , Palmer Christine M , Covington Michael F , Wallace Andreah D , Harmer Stacey L , Maloof Julin N
Published: January 2018

Plants respond to neighbor shade by increasing stem and petiole elongation. Shade, sensed by phytochrome photoreceptors, causes stabilization of PHYTOCHROME INTERACTING FACTOR proteins and subsequent induction of YUCCA auxin biosynthetic genes. To investigate the role of YUCCA genes in phytochrome-mediated elongation we examined auxin signaling kinetics after an end-of-day far-red (EOD-FR) light treatment, and found that an auxin responsive reporter is rapidly induced within 2 hours of far-red exposure. YUCCA2, 5, 8, and 9 are all induced with similar kinetics suggesting that they could act redundantly to control shade-mediated elongation. To test this hypothesis we constructed a yucca2,5,8,9 quadruple mutant and found that the hypocotyl and petiole EOD-FR and shade avoidance are completely disrupted. This work shows that YUCCA auxin biosynthetic genes are essential for detectable shade avoidance and that YUCCA genes are important for petiole shade avoidance.
IVaCS: an Integrated Variant Calling System
Authors: Chiara Matteo , Chillemi Giovanni , D'Antonio Mattia , D'Onorio De Meo Paolo , Flati Tiziano , Gioiosa Silvia , Picardi Ernesto , Pesole Graziano , Castrignanò Tiziana
Published: January 2018

The reduction in sequencing costs associated with next generation sequencing technologies (NGS) has led to a rapid upsurge in the amount of genome re-sequencing data, paving the way for the advent of personalized genomics and precision medicine. Accurate genotyping is crucial for effective analyses of these data, and in particular for the correct identification of candidate causal mutations in diagnostic screenings. The body of genome resequencing data will likely see exponential growth in the next few years, underlining the need for publicly available, accurate and time-effective bioinformatics systems for data analysis. Ideally, such systems should be easy to use and constantly updated as new genomes and software tools are released.

Here we present IVaCS, a fully automated, highly accurate system with a web based graphical interface for genotyping and variant annotation. IVaCS offers state of the art tools for variant calling and annotation along with expert made pipelines for the analysis of whole genome sequencing (WGS), whole-exome sequencing (WES) and targeted resequencing (TGS) data, performing all steps from quality trimming to variant annotation.

The system is specifically designed to assist users with little or no bioinformatics skills and all the pipelines are available through a user friendly web interface. The final output is provided in the form of a dynamic web page where variants can be selected on the base of user defined hard filters. A comprehensive report containing detailed information and statistics concerning the execution of each step of the pipelines is also generated.

Extensive tests on publicly available genome resequencing data (Illumina platinum genome NA12878), show that our system recovers a slightly better sensitivity and a higher specificity than the commercial Illumina VCAT 2.0 software. IVaCS is implemented with a modular architecture and each module (quality trimming, reads mapping, variant calling, variant annotation) can be used independently. IVaCS may manage all the major commercial kits for exome sequencing, such as Illumina, Agilent or Nimblegen, along with a comprehensive collection of reference genomes (all the Illumina genomes, including human, mouse and cow, among the others) with corresponding genomic annotations. Finally, the software leverages an ensemble of publicly available resources (e.g., dbSNP, OMIM, COSMIC and ClinVar among others) for the functional annotation of human variants. Advanced users needing more control over the single steps might also request the command-line version of the software which is more flexible and easy to customize. IVaCS has a very active and growing community. The system is under constant development and new reference genomes, databases and bioinformatics tools are added to IvaCS on a regular basis. IVACS is available at: https://bioinformatics.cineca.it/ivacs
XTENS: a neuroblastoma copy number variation repository at the BIT-Gaslini biobank
Authors: Izzo Massimiliano , Cangelosi Davide , Pezzolo Annalisa , Morini Martina , Varesio Luigi
Published: January 2018

Motivation Neuroblastoma is the major paediatric solid tumour. Unfortunately, about 50% of high risk patients are refractory to treatment and die, demanding new prognostic indicators for improving and personalising therapy. Biomarkers discovery depends on mining molecular, biological, and clinical data, thus making integrated biobanks the ideal collectors of this heterogeneous information and the essential structure for this task.The Biobank Integrating Tissue-genomics of Gaslini Institute, Genova, Italy (BIT-Gaslini) has adopted XTENS [1,2], a web-based data management platform to handle the sample management workflow and integrate it with the patients’ clinical records and molecular data. As of December 2015 the biobank collected over 3700 primary samples (2140 tissue and 1600 fluid) and 1650 derivatives (1030 DNA and 620 RNA). Besides sample management information - such as specimens characterisation, aliquot deliveries to external laboratories and/or centres, and quality control reports - XTENS stored clinical and molecular details for over 900 neuroblastoma patients as retrieved from the National Neuroblastoma Registry and 175 microarray profiles from primary tumour tissues. We have decided to test the capability of the platform as a repository for Copy Number Variations (CNVs, gain/amplification and loss of DNA) data obtained from oligonucleotide array-Comparative Genomic Hybridisation (aCGH) analyses routinely executed at Gaslini Institute. aCGH data are essential for patients' assignment to specific treatments' protocols and they are a valuable source of information for mining the biology of neuroblastoma and the identification of new prognostic indicators. Methods To identify CNVs (numerical and segmental chromosomal alterations) in neuroblastoma samples, we used aCGH, that was performed using the Agilent Human Genome CGH microarrays 180K following the manufacturer’s protocol (Agilent Technologies, Santa Clara, California, USA). Slides were scanned using a G2565BA scanner, and analysed using Agilent CGH Analytics software Genomic Workbench 7.0 (Agilent Technologies Inc.) with the statistical algorithm ADM-1 and a sensitivity threshold of 6.0. Probes with a log ratio value greater than 2 were considered as amplified.To automate the CNV upload to XTENS, we have designed a novel page on the website where the operator can upload the aCGH processed files containing all the analysis metadata and the full list of found aberrations (gain and loss analysis of DNA). A Node.js server-side script parses the uploaded file, and stores all the relevant information in the database. The raw data files are then uploaded using the standard XTENS data management interface and are stored on a distributed file system managed by the iRODS data grid middleware, transparently integrated with XTENS through a REST interface. Results As of March 2016, we have ***Abstract truncated at 3,000 characters - the full version is available in the pdf file***
Investigating the opening mechanism of topoisomerase I B in complex with DNA by means of metadynamics
Authors: Morozzo della Rocca Blasco , Coletta Andrea , Iacovelli Federico , Desideri Alessandro
Published: January 2018

Motivations: Topoisomerases play a central role in DNA homeostasis and act on them through a catalytic cycle that comprises the opening of the protein clamp to embrace the DNA (at the beginning of the cycle) and opening to allow the release of the topologically relaxed substrate. Protein opening is hard to follow experimentally thus computational techniques are very handy in dealing with this transitions, although classical molecular dynamics is limited in following big conformational changes and slowly occurring transitions. Therefore we present a well-tempered Metadynamics study of hToP1 clamp opening in presence of a 22-bp long ds-DNA substrate.

Methods: The protein structure of wild type hTopIB in complex with DNA has been obtained as previously reported. The hTopIB clamp around the DNA molecule has been destabilized by means of metadynamics using Gromacs-4.5.5 with the PLUMEDv1.3 patch. In the simulation, two Collective Variables have been used to describe the clamp opening: the distance between the center of mass of Cα atoms of the lip1 and of the lip2; and the number of hydrogen bonds between the protein and DNA.Free-energy surface (FES) and the minimum energy path (MEP) connecting different minima were reconstructed using in-house written codes in Python. Salt bridge analysis was conducted via Salt bridges extension of the VMD program and other analyses were performed with the tools of the GROMACS package.

Results: Results indicate that the lobes of the protein retain their domain structure during the opening that is characterized by an energy barrier of about 50 Kjoul/mole. Furthermore the DNA remains in contact with the Cap lobe, a fact that would enable the protein to perform 1D-diffusion in the DNA strand to enhance the specific activity by reducing the dimensional space it has to search between relaxation events.
Standard codon substitution models overestimate purifying selection for non-stationary data
Authors: Kaehler Benjamin D , Yap Von Bing , Huttley Gavin A
Published: January 2018

Estimation of natural selection on protein-coding sequences is a key comparative genomics approach for de novo prediction of lineage specific adaptations. Selective pressure is measured on a per-gene basis by comparing the rate of non-synonymous substitutions to the rate of neutral evolution, typically assumed to be the rate of synonymous substitutions. All published codon substitution models have been time-reversible and thus assume that sequence composition does not change over time. We previously demonstrated that if time-reversible DNA substitution models are applied blindly in the presence of changing sequence composition, the number of substitutions is systematically biased towards overestimation. We extend these findings to the case of codon substitution models and further demonstrate that the ratio of non-synonymous to synonymous rates of substitution tends to be underestimated over three data sets of insects, mammals, and vertebrates. Our basis for comparison is a non-stationary codon substitution model that allows sequence composition to change. Model selection and model fit results demonstrate that our new model tends to fit the data better. Direct measurement of non-stationarity shows that bias in estimates of natural selection and genetic distance increases with the degree of violation of the stationarity assumption. Additionally, inferences drawn under time-reversible models are systematically affected by compositional divergence. As genomic sequences accumulate at an accelerating rate, the importance of accurate de novo estimation of natural selection increases. Our results establish that our new model provides a more robust perspective on this fundamental quantity.