bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic laboratory notebooks in a public-private-partnership
Authors: Vaas Lea A.I. , Witt Gesa , Windshügel Björn , Bosin Andrea , Serra Giovanni , Bruengger Adrian , Winterhalter Mathias , Gribbon Philip , Levy-Petelinkar Cindy J. , Kohler Manfred
Published: January 2018

This report shares the experience during selection, implementation and maintenance phases of an electronic laboratory notebook (ELN) in a public private partnership project and comment on user feedback. In particular, we address which time constraints for roll-out of an ELN exist in granted projects and which benefits and/or restrictions come with out-of-the-box solutions. We discuss several options for the implementation of support functions and potential advantages of open access solutions. Connected to that, we identified willingness and a vivid culture of data sharing as the major item leading to success or failure of collaborative research activities. The feedback from users turned out to be the only angle for driving technical improvements, but also exhibited high efficiency. Based on these experiences, we describe best practices for future projects on implementation and support of an ELN supporting a diverse, multidisciplinary user group based in academia, NGOs, and/or for-profit corporations located in multiple time zones.
Ten simple rules for Lightning and PechaKucha presentations.
Authors: Lortie Christopher J
Published: January 2018

An interesting opportunity has emerged that bridges the gap between lengthy, detailed presentations of scientific findings and ‘sound bites’ appropriate for media reporting – very short presentations often presented in sets. Lightning or Ignite (20 slides @15 seconds each) and PechaKucha (20 slides @20 seconds each) presentations are common formats for short, rapid communications at scientific conferences and public events. The simple rules for making good presentations also apply, but these presentation formats provide both unique communication opportunities and novel challenges. In the spirit of light, quick, and exact (but without the fox), here are ten simple rules for presentation formats that do not wait for the speaker.
Developmental toxicity from exposure to various forms of mercury compounds in medaka fish (Oryzias latipes) embryos
Authors: Dong Wu , Liu Jie , Wei Lixin , Jingfeng Yang , Chernick Melissa , Hinton David E.
Published: January 2018

This study examined developmental toxicity of different mercury compounds, including some used in traditional medicines. Medaka (Oryzias latipes) embryos were exposed to 0.001-10 μM concentrations of MeHg, HgCl2, α-HgS (Zhu Sha), and β-HgS (Zuotai) from stage 10 (6-7 hpf) to 10 days post fertilization (dpf). Of the forms of mercury in this study, the organic form (MeHg) proved the most toxic followed by inorganic mercury (HgCl2), both producing embryo developmental toxicity. Altered phenotypes included pericardial edema with elongated or tube heart, reduction of eye pigmentation, and failure of swim bladder inflation. Both α-HgS and β-HgS were less toxic than MeHg and HgCl2. Total RNA was extracted from survivors 3 days after exposure to MeHg (0.1 μM), HgCl2 (1 μM), α-HgS (10 μM), or β-HgS (10 μM) to examine toxicity-related gene expression. MeHg and HgCl2 markedly induced metallothionein (MT) and heme oxygenase-1 (Ho-1), while α-HgS and β-HgS failed to induce either gene. Chemical forms of mercury compounds proved to be a major determinant in their developmental toxicity.
RNA-seq reveals more consistent reference genes for gene expression studies in human non-melanoma skin cancers
Authors: Hoang Van LT , Tom Lisa N , Quek Xiu-Cheng , Tan Jean-Marie , Payne Elizabeth J , Lin Lynlee L , Sinnya Sudipta , Raphael Anthony P , Lambie Duncan , Frazer Ian H , Dinger Marcel E , Soyer H. Peter , Prow Tarl W
Published: January 2018

Identification of appropriate reference genes (RGs) is critical to accurate data interpretation in quantitative real-time PCR (qPCR) experiments. In this study, we have utilised next generation RNA-sequencing (RNA-seq) to analyse the transcriptome of a panel of non-melanoma skin cancer lesions, identifying genes, which are consistently expressed across all samples. Genes encoding ribosomal proteins were amongst the most stable in this dataset. Validation of this RNA-seq data was examined using qPCR to confirm the suitability of a set of highly stable genes for use as RGs. These genes will provide a valuable resource for the normalisation of qPCR data for the analysis of non-melanoma skin cancer.
1H Nuclear magnetic resonance-based metabolomic study for Cabernet Sauvignon wines in different vintages
Authors: Hu Boran , Zhao Qi , Yue Yaqing , Zhu Jiangyu , Lu Guangnian , Li Hua , Zhang Fengmin , Hardie W. J.
Published: January 2018

An 1H NMR-based metabolomic study was used to characterize 2009, 2010, 2011, and 2012 vintages of Cabernet Sauvignon wines from Ningxia that were vinified in the same fermentation technique. The pattern recognition methods of principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) clearly distinguished vintages of wine, driven by the following metabolites: valine,2,3-butanediol, ethyl acetate, proline, succinic acid, lactic acid, acetic acid, glycerol, gallic acid and choline. The PLS-DA loading plots also differentiated between the metabolites of different vintages. The highest levels of valine, 2,3-butanediol, gallic acid and proline were found in the 2009 vintage wines. The 2011 vintage wines contained the highest levels of lactic acid, and the highest levels of ethyl acetate, succinic acid, glycerol and choline were detected in the 2012 vintage wines. A total of 8 metabolites were selected from the 1H NMR spectra and quantified according to their peak areas, yielding concentrations in a greement with the PLS-DA results.
Randomised Badger Culling Trial: Impact, based on more extensive data
Authors: Hendy David
Published: January 2018

In 2007 the Independent Scientific Group (ISG) reported to the UK government the impact on bovine tuberculosis (TB) in cattle of the Randomised Badger Culling Trial (RBCT). Badgers were culled between 1998 and 2005 across 100 km2 (nominal) zones in the West of England. The results were based on a model of New Herd Incidence (NHI). It was concluded that reactive culling generated overall detrimental effects, while proactive culling achieved very modest overall benefits at the cost of elevated incidence in surrounding areas.

This work looks at more extensive RBCT data to examine if these findings hold true. Instead of presenting the results of a model, this work directly illustrates the data. The Animal and Plant Health Agency supplied this data in March 2016. Such data covers a greater number of years (1986 to 2012) and includes the prevalence of herd restrictions as well as herd incidence.

Whilst the proactive culls substantially and sustainably reduced cattle TB in treated areas, such culls did not significantly increase TB in the surrounding areas. NHIs between 2006 and 2012 dropped by 28%, 1% and 18% in the treated, outer 2km ring, and combined areas respectively. Based on the number of NHIs prevented since 1998 in the combined area, a break-even cost to complete a badger removal exercise was calculated to be £8,693 per km2. This figure may be under-estimated because it takes no account of any NHIs prevented after 2012.

The more limited reactive culls had no impact on both the treated area and outer 2km ring. Proactive culling only reduced confirmed TB with no significant impact on unconfirmed TB.

Conclusions in the RBCT Final Report, which were based on the results of a model of time-shifted early data, poorly reflect the overall greater benefits seen in this more extensive data. Badger culling is highly contentious in the UK and many press reports adversely report the effectiveness of badger culling in general and the culls which started in 2013 in particular. The RBCT conclusions are often cited to add credence to these press reports. After the first year of substantial culling in the RBCT, this work found that 9 years of data were needed to clearly see the full extent by which TB dropped when plotted against calendar year. This delay should be reflected on when accounting for the circumstances and assessing impact of the 2013 culls.

This work was restricted to looking at data showing total TB breakdowns over all zones. Further work to examine breakdowns by zone or groups of zones may reveal more.
Randomised Badger Culling Trial: Impact, based on more extensive data
Authors: Hendy David
Published: January 2018

In 2007 the Independent Scientific Group (ISG) reported to the UK government the impact on bovine tuberculosis (TB) in cattle of the Randomised Badger Culling Trial (RBCT). Badgers were culled between 1998 and 2005 across 100 km2 (nominal) zones in the West of England. The results were based on a model of confirmed New Herd Incidence (NHI). It was concluded that reactive culling generated overall detrimental effects, while proactive culling achieved very modest overall benefits at the cost of elevated incidence in surrounding areas.

This work looks at more extensive RBCT data to examine if these findings hold true. Instead of presenting the results of a model, this work directly illustrates the data. The Animal and Plant Health Agency supplied this data in March 2016. Such data covers a greater number of years (1986 to 2012) and includes the prevalence of herd restrictions as well as herd incidence.

Whilst the proactive culls substantially reduced confirmed NHI in treated areas, such culls did not significantly increase NHI in the surrounding outer ring. In fact, between 1998 and 2012 these NHI slightly reduced in the outer ring . Between 2006 and 2012 they dropped by 28%, 1% and 18% in the treated, outer 2km ring, and combined areas respectively. Based on the total number of confirmed NHIs prevented between 1998 and 2012, a break-even cost to complete a badger removal exercise was calculated to be £8,693 per km2 with benefits continuing in 2012.

Proactive culling only reduced confirmed NHIs with no significant impact on unconfirmed NHIs. The more limited reactive culls had no impact on both the treated area and the outer 2km ring.

Conclusions in the RBCT Final Report, which were based on the results of a model of time-shifted early data, poorly reflect the overall greater benefits seen in this more extensive data. Badger culling is highly contentious in the UK and many press reports adversely report the effectiveness of badger culling in general and the culls which started in 2013 in particular. The RBCT conclusions are often cited to add credence to these press reports. After the first year of substantial culling in the RBCT, this work found that 9 years of data were needed to clearly see the full extent by which TB dropped when plotted against calendar year. This delay should be reflected on when accounting for the circumstances and assessing impact of the 2013 culls.

This work was restricted to looking at data showing total TB breakdowns over all zones. Further work to examine breakdowns by zone or groups of zones may reveal more.
Meiotic shugoshins differ from mitotic ones by arginine-reach C-terminal motif in yeast, plant, animals, and human
Authors: Grishaeva Tatiana M , Kulichenko Darya , Bogdanov Yuri F
Published: January 2018

Background. Shugoshins (SGOs) are proteins that protect cohesins located at the centromeres of sister chromatids from their early cleavage during mitosis and meiosis in plants, fungi, and animals. Their function is to prevent premature sister-chromatid disjunction and segregation. Meiotic SGOs prevent segregation of sister chromatids in meiosis I, thus permitting homologous chromosomes to segregate and reduce chromosome number to haploid set. The study focused on the structural differences among shugoshins acting during mitosis and meiosis that cause differences in chromosome behavior in these two types of cell division in different organisms.

Methods. A bioinformatics analysis of protein domains, conserved amino acid motifs, and physicochemical properties of 32 proteins from 25 species of plants, fungi, and animals was performed.

Results. We identified a C-terminal arginine-reach amino acid motif that is highly evolutionarily conserved among the shugoshins protecting centromere cohesion of sister chromatids in meiotic anaphase I, but not among mitotic shugoshins. The motif looks like “arginine comb” capable of interaction by hydrogen bonds with guanine bases in the small groove of DNA helix. Shugoshins in different eukaryotic kingdoms differ also in the sets and location of amino acid motifs and the number of α-helical regions in the protein molecule.

Discussion. Meiosis-specific arginine-reach motif may be responsible for formation of SGO-DNA nucleoprotein complex, thus protecting meiotic shugoshins from degradation during meiotic metaphase I and anaphase I, while mitotic SGOs have a motif with less number of arginine residues. This structural difference between meiotic and mitotic shugoshins, probably, could be a key molecular element of the prolonged shugoshin resistance to degradation during meiotic metaphase I and anaphase I and be one of the molecular elements causing the difference in chromosome behavior in meiosis and mitosis. The finding of differences in SGO structure in plant, fungi and animals supports idea of independent evolution of meiosis in different lineages of multicellular organisms.
Intertidal barnacle recruitment in Nova Scotia (Canada) between 2005–2016: relationships with sea surface temperature and phytoplankton abundance
Authors: Scrosati Ricardo A , Ellrich Julius A
Published: January 2018

On the Gulf of St. Lawrence coast of Nova Scotia (Canada), recruitment of the barnacle Semibalanus balanoides occurs in May and June. Every year in June between 2005 and 2016, we recorded recruit density for this barnacle at the same wave-exposed rocky intertidal location on this coast. During these 12 years, mean recruit density was lowest in 2015 (198 recruits dm-2) and highest in 2007 (969 recruits dm-2). The highest recruit density observed in a single quadrat was 1457 recruits dm-2 (in 2011) and the lowest density was 34 recruits dm-2 (in 2015). Most barnacle recruits appear during May, which suggests that most pelagic larvae, which develop over five-to-six weeks and originate the recruits, are in the water column in April. A model selection approach identified sea surface temperature (SST) in April and the abundance of phytoplankton (food for barnacle larvae, measured as chlorophyll-a concentration –Chl-a–) in April as good explanatory variables. Together, April SST and Chl-a explained 51 % of the observed interannual variation in recruit density with an overall positive influence. April SST was positively related to March–April air temperature. April Chl-a was negatively related to the April ratio between the number of days with onshore winds (which blow from phytoplankton-limited offshore waters) and the number of days with alongshore winds (coastal phytoplankton is higher on coastal waters). Therefore, these observations suggest that climatic processes affecting April SST and Chl-a indirectly influence intertidal barnacle recruitment by influencing larval performance.
The underestimation of global microbial diversity
Authors: Lennon Jay T , Locey Kenneth J
Published: January 2018

In a recent commentary, Amann and Rosselló-Mórab summarize how the census of Bacteria and Archaea has changed over time (1). For decades, the number of recognized microbial taxa was underestimated owing to limitations associated with culture-based methods and the rules of nomenclature. The authors describe a "quantum leap" in the estimates of global microbial diversity following advances in high-throughput sequencing technology. Despite this, Amann and Rosselló-Mórab project that a complete census of microbial diversity will be reached within a few years culminating in the lower millions of taxa (1). While perhaps attractively optimistic to some, this presumption is misleading for the following reasons.
Determination of histamine levels in long-tail tuna (Thunnus tonggol) stored at different temperature
Authors: Mahusain Nurul Aina Syuhada , Bayoi Fernandes , Karim Nurul Ulfah , Zainol Mohd Khairi , Danish-Daniel Muhd
Published: January 2018

Histidine is precursor for histamine (4-(2-aminoethyl) imidazole) formation through a process called decarboxylation with the aid of histidine decarboxylase enzyme possessed by particular bacterial species. Since storage temperature is highly influenced the formation of histamine, a study regarding histamine and bacterial count was conducted. Long-tail tuna was stored at -20, 4, 15, 25 and 37 ̊C and analysis of bacteria and histamine was done for every 48 hours till reaching 196 hours for freezing and chilling storage temperature. Histamine determination and bacterial count was taken for every 0, 6, 12,18 and 24 hours for 15, 25 and 37 ̊C. At 0 day of storage for -20̊ C, gut and non gut fish samples showed histamine level of 3.496 mg/100. Reduction of histamine levels took place after 48 hours of storage but increased later throughout the storage period up to 8 days, reaching a value of 4.84 and 3.78 mg/100 g for gut and non gut tuna, respectively. Similar trend of result was seen at 4 ̊C where a gradual increase of histamine concentration was observed throughout the storage period. However, the histamine level in gut tuna exceeded the safety level at day 8. At temperature 15 and 25 ̊C, the gut fish meat is not safe for consumption at 24 hours. Meanwhile, the safety limit can be seen within 12 hours and 18 hours of storage in gut and non gut fish stored at 37 ̊C, respectively. For bacterial cell enumeration, at -20 ̊C, the initial count of bacteria is 5.4 Log CFU/g for both fish condition. The count then slightly increased to 6.28 and 5.91 for gutted and non gutted respectively at 48 hours till reaching last storage time. Similar trend was recorded at 4, 15, 25 and 37 ̊C from time to time. However, bacterial count is largely seen at 37 ̊C. This may be due to the presence of spoilage bacteria that can deteriorate the quality of fish.
Hypergravity hinders axonal development of motor neurons in Caenorhabditis elegans
Authors: Kalichamy Saraswathi Subbammal , Lee Tong Young , Yoon Kyoung-hye , Lee Jin Il
Published: January 2018

As space flight becomes more accessible in the future, humans will be exposed to gravity conditions other than our 1G environment on Earth. Changes in physiology and anatomy in altered gravity conditions have long been observed, especially the loss of muscle mass during long-term space habitation, the reason for which is not fully understood. Although much effort has gone into studying the effects of gravity in muscle physiology, its effect on the development of neurons has not been thoroughly assessed. Using the nematode model organism Caenorhabditis elegans, we examined changes in response to hypergravity in the development of the 19 GABAergic DD/VD motor neurons that innervate body muscle. We found that a high gravity force above 10G significantly increases the number of animals with defects in the development of axonal projections from the DD/VD neurons. We showed that a critical period of hypergravity exposure during the embryonic/early larval stage was sufficient to induce defects. While characterizing the nature of the axonal defects, we found that in normal 1G gravity conditions, DD/VD axonal defects occasionally occurred, with the majority of defects occurring on the dorsal side of the animal and in the mid-body region, and a significantly higher rate of error in the 13 VD axons than the 6 DD axons. Hypergravity exposure increased the rate of DD/VD axonal defects, but did not change the distribution or the characteristics of the defects. Our study demonstrates that in addition to gravity’s effects on muscle development, gravity can also impact motor neuron development.
Size matters: relationships between body size, dry weight and ash-free dry weight of common coastal, aquatic invertebrates in the Baltic Sea
Authors: Eklöf Johan , Austin Åsa , Bergström Ulf , Donadi Serena , Eriksson Britas D H K , Hansen Joakim , Sundblad Göran
Published: January 2018

Background. Organism biomass is one of the most important variables in ecological studies, making estimations of organism weight one of the most common laboratory tasks. Biomass of small macroinvertebrates is usually estimated as dry (DW) or ash-free dry weight (AFDW); a laborious and time consuming process, that often can be speeded up using easily measured and reliable proxy variables like wet/fresh weight and/or body size. Another common way of estimating AFDW - which is the most accurate but also time-consuming estimate of biologically active tissue weight - is the use of AFDW/DW ratios or conversion factors. So far, however, these ratios typically ignore the possibility that the relative weight of biologically active vs. non-active support tissue (e.g. protective exoskeleton or shell) - and therefore, also the AFDW/DW ratio - may change with body size, as previously shown for taxa like spiders, vertebrates and trees.

Methods. We collected samples of aquatic, epibenthic macroinvertebrates (>1 mm) in 32 shallow bays along a 360 km stretch of the Swedish coast along the Baltic Sea; one of the largest brackish water bodies on Earth. We then estimated statistical relationships between the body size (length or height in mm), dry weight and ash-free dry weight for 14 of the most common taxa; five gastropods, three bivalves, three crustaceans and three insect larvae. Finally, we statistically estimated the potential influence of body size on the AFDW/DW ratio per taxon.

Results. For most of the taxa, non-linear regression models describing the power relationship between body size and i) DW and ii) AFDW fit the data well (as indicated by low SE and high R2). Moreover, for more than half of the taxa studied (including the vast majority of the shelled molluscs), body size had a negative influence on organism AFDW/DW ratios.

Discussion. The good fit of the modelled power relationships suggest that the constants reported here can be used to more quickly estimate organism dry- and ash-free dry weight based on body size, thereby freeing up considerable work resources. However, the considerable differences in constants between taxa emphasize the need for taxon-specific relationships, and the potential dangers associated with either ignoring body size or substituting relationships between taxa. The negative influence of body size on AFDW/DW ratio found in a majority of the molluscs could be caused by increasingly thicker shells with organism age, and/or spawning-induced loss of biologically active tissue in adults. Consequently, future studies utilizing AFDW/DW (and presumably also AFDW/wet weight) ratios should carefully assess the potential influence of body size to ensure more reliable estimates of organism biomass.
Transcriptomic response of maize primary roots to low temperatures at seedling emergence
Authors: Di Fenza Mauro , Hogg Bridget , Grant Jim , Barth Susanne
Published: January 2018

Background. Maize (Zea mays) is C 4 tropical cereal and its adaptation to temperate climates can be problematic due to low soil temperatures at early stages of establishment. Methods. We report on a physiological and transcriptomic experiment on twelve maize varieties from a chilling condition adapted gene pool which identified four genotypes with significant contrasting chilling tolerance.These four varieties were subject to microarray analysis to identify up and down regulated genes under chilling conditions. Results. Stress induced by low temperature in the varieties Picker,PR39B29, Fergus and Codisco was reflected only in the expression profiles of the varieties Picker and PR39B29. No significant changes in expression were observed in Fergus and Codisco upon chilling stress. The overall number of genes up and down regulated in the two chilling tolerant varieties amounted to69. These two varieties exhibited two different trancriptomic patterns in which only four genes were shared, although not all with the same degree of regulation. Overall the expression pattern was similar between the two chilling tolerant varieties, indicating a common response to chilling stress. Discussion. Varieties with an enhanced root/shoot growth ratio under low temperature were more tolerant which could be an early and inexpensive measure for germ plasm screening. We have identified novel cold inducible genes in an already adapted maize breeding gene pool. This illustrates that further varietal selection for enhanced chilling tolerance is possible in an already preselected gene pool.
Stopping duplicate bug reports before they start with Continuous Querying for bug reports
Authors: Hindle Abram
Published: January 2018

Bug deduplication is a hot topic in software engineering information retrieval research, but it is often not deployed. Typically to de-duplicate bug reports developers rely upon the search capabilities of the bug report software they employ, such as Bugzilla, Jira, or Github Issues. These search capabilities range from simple SQL string search to IR-based word indexing methods employed by search engines. Yet too often these searches do very little to stop the creation of duplicate bug reports. Some bug trackers have more than 10\% of their bug reports marked as duplicate. Perhaps these bug tracker search engines are not enough? In this paper we propose a method of attempting to prevent duplicate bug reports before they start: continuous querying. That is as the bug reporter types in their bug report their text is used to query the bug database to find duplicate or related bug reports. This continuous querying allows the reporter to be alerted to duplicate bug reports as they report the bug, rather than formulating queries to find the duplicate bug report. Thus this work ushers in a new way of evaluating bug report deduplication techniques, as well as a new kind of bug deduplication task. We show that simple IR measures show some promise for addressing this problem but also that further research is needed to refine this novel process that is integrate-able into modern bug report systems.
Randomised Badger Culling Trial: How big was the perturbation effect?
Authors: Hendy David
Published: January 2018

In a report issued to the UK government in 2007 on the Randomised Badger Culling Trial (RBCT), it was stated that the incidence of bovine tuberculosis (TB) in cattle increased in areas surrounding where badgers were removed. It is known that badger culling perturbs badgers and this leads to increased TB transmission in and around these treated areas. The increase in TB in the surrounding areas was attributed to this process.

In this study of the RBCT analysis it was found that large TB increases in areas surrounding proactively treated areas depended heavily on adjustments made for pre-cull history. This work looks at the basis for applying these adjustments. Since it is not possible to remove statistical error in the data, which confidence intervals suggest may have been large, it is argued that it was unsafe to apply these adjustments. As such it is argued that TB increases due to perturbation in the report presented to the UK government in 2007 may have been over-estimated.
Age and anthropometric variables and success in mixed martial arts
Authors: Kirk Christopher
Published: January 2018

Anthropometry and chronological age has been demonstrated to have an effect on individual performance in competitive sport, with the relationship between stature and wingspan being found to be selective criteria in many sports, although evidence for this in MMA is negligible. In this study, n = 278 professional MMA bouts were analysed with the winners and losers being compared in terms of chronological age, stature, wingspan, stature-to-wingspan ratio (S:W) and method of win/loss using paired samples t tests, Wilcoxon signed-rank tests, one way ANOVAs, Kruskal-Wallis tests (all ≤ .05) and Bayes Factor (BF 10 ). The results showed that for the most part anthropometric differences have no effect on who wins the bout, but taller bout losers are most likely to lose via strikes. Across the full cohort and several competitive divisions, it was found that older participants are significantly more likely to lose, and are also significantly more likely to lose via strikes. Participants who won via decision were found to be significantly older than those who won via strikes or submission.
RGFA: powerful and convenient handling of assembly graphs
Authors: Gonnella Giorgio , Kurtz Stefan
Published: January 2018

The “Graphical Fragment Assembly” (GFA) is an emerging format for the representation of sequence assembly graphs, which can be adopted by both de Bruijn graph- and string graph-based assemblers. Here we present RGFA, an implementation of the proposed GFA specification in Ruby. It allows to conveniently parse, edit and write GFA files. Complex operations such as the separation of the implicit instances of repeats and the merging of linear paths can be performed. A typical application of RGFA is the editing of a graph, to finish the assembly of a sequence, using information not available to the assembler. We illustrate a use case, in which the assembly of a repetitive metagenomic fosmid insert was completed using a script based on RGFA. Furthermore, we show how the API provided by RGFA allows to design complex graph editing algorithms. As an example, we developed a detection algorithm for CRISPRs in a de Bruijn graph. Finally, RGFA can be used for comparing assembly graphs, e.g. to document the changes in a graph after applying a GUI editor. A program, GFAdiff is provided, which compares the information in two graphs, and generate a report or a Ruby script documenting the transformation steps between the graphs.
Improving ancient DNA genome assembly
Authors: Seitz Alexander , Nieselt Kay
Published: January 2018

Most reconstruction methods for genomes of ancient origin that are used today require a closely related reference. In order to identify genomic rearrangements or the deletion of whole genes, de novo assembly has to be used. However, because of inherent problems with ancient DNA, its de novo assembly is highly complicated. In order to tackle the diversity in the length of the input reads, we propose a two-layer approach, where multiple assemblies are generated in the first layer, which are then combined in the second layer. We used this two-layer assembly to generate assemblies for an ancient sample and compared the results to current de novo assembly approaches. We are able to improve the assembly with respect to the length of the contigs and can resolve more repetitive regions.
An integrative computational framework for personalized detection of tumor epitopes in melanoma immunotherapy
Authors: Jaitly Tanushree , Schaft Niels , Doerrie Jan , Gross Stefanie , Schuler-Thurner Beatrice , Wolkenhauer Olaf , Schuler Gerold , Taher Leila , Gupta Shailendra , Vera Julio
Published: January 2018

In aggressive solid tumors like melanoma, a strategy for therapy personalization can be achieved by combining high-throughput data on the patient’s specific tumor mutation and expression profiles. A remarkable case is dendritic cell-based immunotherapy, where tumor epitopes identified from the patient’s specific mutation profiles are loaded on patient-derived mature dendritic cells to stimulate cytotoxic T cell mediated anticancer immunity. Here we present a personalized computational pipeline for the selection of tumor-specific epitopes based on 1) patient specific haplotype; 2) cancer associated mutations; and 3) expression profiles of mutation carrying genes. We applied our workflow to one melanoma patient. Specifically, we analyzed tumor whole exome sequencing and RNA sequencing data to first detect tumor-specific mutations followed by epitope prediction based on the patient’s HLA haplotype and filtering of epitopes using expression profile and binding affinity. We performed docking studies to predict the best set of epitopes targeting the patient’s alleles. The proposed workflow enables us to find personalized tumor-specific epitopes for stimulating cytotoxic T-cell responses.
Evidence for high inter-generational individual quality in yellow-eyed penguins
Authors: Stein Aviva M , Young Melanie J. , Darby John , Seddon Philip John , van Heezik Yolanda
Published: January 2018

Longitudinal studies focusing on lifetime reproductive success (LRS) have been used to measure individual breeding performance and identify commonalities among successful breeders. By extending the focus to subsequent generations we identify a proportion of high-quality individuals that contribute disproportionately to the population over multiple generations. We used 23 years of yellow-eyed penguin (Megadyptes antipodes) breeding data from one breeding area to identify the proportion of individual birds that raised successful breeders, which in turn raised offspring that bred successfully. We explored which life-history components influenced lifetime reproductive success, as this knowledge would enable conservation resources to be focused on high-performing individuals in this endangered population. From 2147 birds marked as chicks, 370 (17.2%) survived to adulthood and recruited to their natal location, of which 219 (10.2%) fledged offspring: 124 (56.6%) of the 219 birds produced offspring that recruited as breeders. Only 102 birds (4.8% of 2147) fledged first-generation offspring that in turn fledged offspring (second-generation offspring, or grand-offspring). We found that c. 26% of the birds that survived to breed had above-average LRS as well as above-average numbers of grand-offspring, and were more likely to have produced first-generation chicks that recruited and also produced above-average numbers of second-generation chicks. Our findings suggest that there is a core of “super-breeders” that contribute disproportionately to the population over successive generations. Lifespan and age-at-first-breeding were correlated with LRS. We suggest that traits of birds relating to longevity, health (e.g. immunocompetence) and fitness could be examined to identify potential links with high LRS and inter-generational fecundity. “Super-breeders” appear to consistently balance high LRS with long- life-span in a stochastic environment, demonstrating greater resilience in the face of extreme events.
Analyzing and characterization of the chloroplast genome of Salix suchowensis
Authors: Sun Congrui , Li Jie , Dai Xiaogang , Chen Yingnan
Published: January 2018

By screening sequence reads from the chloroplast (cp) genome of S. suchowensis that generated by the next generation sequencing platforms, we built the complete circular pseudomolecule for its cp genome. This pseudomolecule is 155,508 bp in length, which has a typical quadripartite structure containing two single copy regions, a large single copy region (LSC 84,385 bp), and a small single copy region (SSC 16,209 bp) separated by inverted repeat regions (IRs 27,457 bp). Gene annotation revealed that the cp genome of S. suchowensis encoded 119 unique genes, including 4 ribosome RNA genes, 30 transfer RNA genes, 82 protein-coding genes and 3 pseudogenes. Analyzing the repetitive sequences detected 15 tandem repeats, 16 forward repeats and 5 palindromic repeats. In addition, a total of 188 perfect microsatellites were detected, which were characterized as A/T predominance in nucleotide compositions. Significant shifting of the IR/SSC boundaries was revealed by comparing this cp genome with that of other rosids plants. We also built phylogenetic trees to demonstrate the phylogenetic position of S. suchowensis in Rosidae, with 66 orthologous protein-coding genes presented in the cp genomes of 32 species. By sequencing 30 amplicons based on the pseudomolecule, experimental verification achieved accuracy up to 99.84% for the cp genome assembly of S. suchowensis. In conclusion, this study built a high quality pseudomolecule for the cp genome of S. suchowensis, which is a useful resource for facilitating the development of this shrub willow into a more productive bioenergy crop.
Exploring the binding properties and structural stability of an opsin in the chytrid Spizellomyces punctatus using comparative and molecular modeling
Authors: Ahrendt Steven R , Medina Edgar Mauricio , Chang Chia-en A , Stajich Jason E
Published: January 2018

Background. Opsin proteins are seven transmembrane receptor proteins which detect light. Opsins can be classified into two types and share little sequence identity: type 1, typically found in bacteria, and type 2, primarily characterized in metazoa. The type 2 opsins (Rhodopsins) are a subfamily of G-protein coupled receptors (GPCRs), a large and diverse class of seven transmembrane proteins and are generally restricted to metazoan lineages. Fungi use light receptors including opsins to sense the environment and transduce signals for developmental or metabolic changes. Opsins characterized in the Dikarya (Ascomycetes and Basidiomycetes) are of the type 1 bacteriorhodopsin family but the early diverging fungal lineages have not been as well surveyed. We identified by sequence similarity a rhodopsin-like GPCR in genomes of early diverging chytrids and examined the structural characteristics of this protein to assess its likelihood to be homologous to animal rhodopsins and bind similar chromophores.

Methods. We used template-based structure modeling, automated ligand docking, and molecular modeling to assess the structural and binding properties of an identified opsin-like protein found in Spizellomyces punctatus, a unicellular, flagellated species belonging to Chytridiomycota, one of the earliest diverging fungal lineages. We tested if sequence and inferred structure were consistent with a solved crystal structure of a type 2 rhodopsin from the squid Todarodes pacificus.

Results. Our results indicate that the Spizellomyces opsin has structural characteristics consistent with functional animal type 2 rhodopsins and is capable of maintaining a stable structure when associated with the retinaldehyde chromophore, specifically the 9-cis­-retinal isomer. Together, these results support further the homology of Spizellomyces opsins to animal type 2 rhodopsins.

Discussion. This represents the first test of structure/function relationship of a type 2 rhodopsin identified in early branching fungal lineages, and provides a foundation for future work exploring pathways and components of photoreception in early fungi.
The GRIMMER test: A method for testing the validity of reported measures of variability
Authors: Anaya Jordan
Published: January 2018

GRIMMER (Granularity-Related Inconsistency of Means Mapped to Error Repeats) builds upon the GRIM test and allows for testing whether reported measures of variability are mathematically possible. GRIMMER relies upon the statistical phenomenon that variances display a simple repetitive pattern when the data is discrete, i.e. granular. This observation allows for the generation of an algorithm that can quickly identify whether a reported statistic of any size or precision is consistent with the stated sample size and granularity. My implementation of the test is available at PrePubMed (http://www.prepubmed.org/grimmer) and currently allows for testing variances, standard deviations, and standard errors for integer data. It is possible to extend the test to other measures of variability such as deviation from the mean, or apply the test to non-integer data such as data reported to halves or tenths. The ability of the test to identify inconsistent statistics relies upon four factors: (1) the sample size; (2) the granularity of the data; (3) the precision (number of decimals) of the reported statistic; and (4) the size of the standard deviation or standard error (but not the variance). The test is most powerful when the sample size is small, the granularity is large, the statistic is reported to a large number of decimal places, and the standard deviation or standard error is small (variance is immune to size considerations). This test has important implications for any field that routinely reports statistics for granular data to at least two decimal places because it can help identify errors in publications, and should be used by journals during their initial screen of new submissions. The errors detected can be the result of anything from something as innocent as a typo or rounding error to large statistical mistakes or unfortunately even fraud. In this report I describe the mathematical foundations of the GRIMMER test and the algorithm I use to implement it.
GenomeHubs: Simple containerised setup of a custom Ensembl database and web server for any species
Authors: Challis Richard J , Kumar Sujai , Stevens Lewis , Blaxter Mark
Published: January 2018

As the generation and use of genomic datasets is becoming increasingly common in all areas of biology, the need for resources to collate, analyse and present data from one or more genome projects is becoming more pressing. The Ensembl platform is a powerful tool to make genome data and cross-species analyses easily accessible through a web interface and a comprehensive API. Here we introduce GenomeHubs, which provide a containerised environment to facilitate the setup and hosting of custom Ensembl genome browsers. This simplifies mirroring of existing content and import of new genomic data into the Ensembl database schema.GenomeHubs also provide a set of analysis containers to decorate imported genomes with results of standard analyses and functional annotations and support export to flat files, including EMBL format for submission of assemblies and annotations to INSDC.Database URL: http://GenomeHubs.org
Predicting enhancers using a small subset of high confidence examples and co-training
Authors: Huska Matthew R , Ramisch Anna , Vingron Martin , Marsico Annalisa
Published: January 2018

Enhancers are important regulatory regions located throughout the genome, primarily in non-coding regions. Several experimental methods have been developed over the last several years to identify their location, but the search space is large and the overlap between the putative enhancer identified using these methods tends to be very small. Computational methods for enhancer prediction often use one large set of experimentally identified enhancer regions as input, and therefore rely critically on their correctness. We chose to take a different approach, and start with a high confidence set of 21 enhancer that are in the intersection of enhancers identified using three completely unrelated experimental approaches: deepCAGE, HiCap and classical enhancer reporter assays. Because this starting set is so small, we use a semi-supervised approach called co-training rather than a fully supervised approach to progressively predict enhancers from unlabeled regions. Using this approach we are able to outperform supervised learning as well as simpler semi-supervised learning methods and achieve an average area under the ROC curve of 0.84.
Sometimes noise is beneficial: stream noise informs vocal communication in the little torrent frog
Authors: Zhao Longhui , Wang Jichao , E. Brauth Steven , Tang Yezhong , Cui Jianguo
Published: January 2018

Many animal species use acoustic signals for social communication including attracting mates, defending resources and assessing risks. Nevertheless, a variety of ambient noise sources often interfere with sound communication and efficient decision making. In the present study we identified an exception to this generalization in a streamside species, the little torrent frog (Amolops torrentis) which communicates in an environment in which stream noise is always present. To show that stream noise can act as a biological signal which reflects the character of the microhabitat of the sender, we performed female phonotaxis experiments using synthetic male advertisement calls. Calls with high dominant frequency exceeding the ambient stream noise band and calls with lower dominant frequency centered at the frequency range of best hearing were used. The signal-noise ratio was varied by adding noise to each kind of call. We found that females prefer calls with high amplitude stream noise added to those with low amplitude stream noise added for both the high and low dominant frequency stimulus pairs; however, the sound of running water had no attractiveness in the absence of calls. These results show that stream noise can function as an information source by enhancing the attractiveness of calls in the torrent frog. Stream noise associates closely with rocks, topographies and vegetation; thus the sound of running water may provide useful information to signal receivers about variations in microhabitats and thereby act on sexual selection under some circumstances. These data therefore contribute to our understanding of how the perception of mate attractiveness in heterogeneous ecological environments can evolve.
Positive effect of dietary lutein and cholesterol on the undirected song activity of an opportunistic breeder
Authors: Casagrande Stefania , Pinxten Rianne , Zaid Erika , Eens Marcel
Published: January 2018

Song is a sexually selected trait that is thought to be an honest signal of the health condition of an individual in many bird species. For species that breed opportunistically, the quantity of food may be a determinant of singing activity. However, it is not yet known whether the quality of food plays an important role in this respect. The aim of the present study was to experimentally investigate the role of two calorie-free nutrients (lutein and cholesterol) in determining the expression of a sexually selected behavior (song rate) and other behaviors (locomotor activity, self-maintenance activity, eating and resting) in male zebra finches (Taeniopygia guttata). We predicted that males supplemented with lutein and cholesterol would sing at higher rates than controls because both lutein and cholesterol have important health-related physiological functions in birds and birdsong mirrors individual condition. To control for testosterone secretion that may upregulate birdsong, birds were exposed to a decreasing photoperiod. Our results showed that control males down-regulated testosterone in response to a decreasing photoperiod, while birds treated with lutein or cholesterol maintained a constant singing activity. Both lutein- and cholesterol-supplemented groups sang more than control groups by the end of the experiment, indicating that the quality of food can affect undirected song irrespective of circulating testosterone concentrations. None of the other measured behaviors were affected by the treatment, suggesting that, when individuals have full availability of food, sexually selected song traits are more sensitive to the effect of food quality than other behavioral traits. Overall the results support our prediction that undirected song produced by male zebra finches signals access to high-quality food.