bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction the first gene co-expression-based interactome in cattle
Authors: Chen Yan , Liu Yining , Du Min , Zhang Wengang , Gao Xue , Zhang Lupei , Gao Huijiang , Xu Lingyang , Li Junya , Zhao Min
Published: January 2018

Integrating genomic information into cattle breeding is an important approach to exploring the molecular mechanism for complex traits related to diary and meat production. To assist with genomic-based selection, a reference map of interactome is needed to fully understand genotype-phenotype relationships. To this end we constructed a co-expression analysis of 92 tissues and this represents the first systematic exploration of gene-gene relationship in cattle. By using robust WGCNA (Weighted Gene Correlation Network Analysis), we described the gene co-expression network of 13,405 protein-coding genes from the cattle genome. Using the 5,000 genes with majority variations in expression across 92 tissues, we compiled a network with 72,306 co-associations and that provides functional insights into thousands of poorly characterized proteins. Further module identifications found 55 highly organized functional clusters representing diverse cellular activities. To demonstrate the re-use of our interaction for functional genomics analysis, we extracted a sub-network associated with DNA binding genes in cattle. The subnetwork was enriched within regulation of transcription from RNA polymerase II promoter representing central cellular functions. In addition, we identified 28 novel linker genes associated with more than 100 DNA binding genes. Our WGCNA-based co-expression network reconstruction will be a valuable resource for exploring the molecular mechanisms of incompletely characterized proteins and for elucidating larger-scale patterns of functional modulization in the cattle genome.
rentrez: An R package for the NCBI eUtils API
Authors: Winter David J
Published: January 2018

The USA National Center for Biotechnology Information (NCBI) is one of the world’s most important sources of biological information. NCBI databases like PubMed and GenBank contain millions of records describing bibliographic, genetic, genomic, and medical data. Here I present rentrez, a package which provides an R interface to 50 NCBI databases. The package is well-documented, contains an extensive suite of unit tests and has an active user base. The programmatic interface to the NCBI provided by rentrez allows researchers to query databases and download or import particular records into R sessions for subsequent analysis. The complete nature of the package, its extensive test-suite and the fact the package implements the NCBI’s usage policies all make rentrez a powerful aid to developers of new packages that perform more specific tasks.
How R helps Airbnb make the most of its data
Authors: Bion Ricardo , Chang Robert , Goodman Jason
Published: January 2018

At Airbnb, R has been amongst the most popular tools for doing data science in many different contexts, including generating product insights, interpreting experiments, and building predictive models. In a recent survey of the Airbnb team, 73% of Data Scientists and Analysts rated themselves as closer to “Expert” than “Beginner” in using R, and 58% regularly use R as a language for data analysis. Airbnb supports R usage by creating internal R tools and by creating a community of R users. At the end of the post, the authors provide some specific advice for practitioners who wish to incorporate R into their day-to-day workflow.
Data organization in spreadsheets
Authors: Broman Karl W , Woo Kara H.
Published: January 2018

Spreadsheets are widely used software tools for data entry, storage, analysis, and visualization. Focusing on the data entry and storage aspects, this paper offers practical recommendations for organizing spreadsheet data to reduce errors and ease later analyses. The basic principles are: be consistent, write dates like YYYY-MM-DD, don't leave any cells empty, put just one thing in a cell, organize the data as a single rectangle (with subjects as rows and variables as columns, and with a single header row), create a data dictionary, don't include calculations in the raw data files, don't use font color or highlighting as data, choose good names for things, make backups, use data validation to avoid data entry errors, and save the data in plain text file.
Forecasting at scale
Authors: Taylor Sean J , Letham Benjamin
Published: January 2018

Forecasting is a common data science task that helps organizations with capacity planning, goal setting, and anomaly detection. Despite its importance, there are serious challenges associated with producing reliable and high quality forecasts — especially when there are a variety of time series and analysts with expertise in time series modeling are relatively rare. To address these challenges, we describe a practical approach to forecasting “at scale” that combines configurable models with analyst-in-the-loop performance analysis. We propose a modular regression model with interpretable parameters that can be intuitively adjusted by analysts with domain knowledge about the time series. We describe performance analyses to compare and evaluate forecasting procedures, and automatically flag forecasts for manual review and adjustment. Tools that help analysts to use their expertise most effectively enable reliable, practical forecasting of business time series.
Bat research efforts in the Philippines: a post-millennium review to identify future research prospects and priorities
Authors: Tanalgo Krizler C , Hughes Alice C
Published: January 2018

Empirical evidence is important to develop effective conservation policies. The documentation and assessment of the status and threats towards a species and its habitat are essential steps toward developing appropriate policies to protect its population and mitigate existing to prevent future extinction. Bats are the example of taxa imperilled with the changing environment coupled with continuous human encroachment on its known habitats. Here, we summarize recent bat research in the Philippines using a bibliographic approach to assess progress and gaps both in different bat research areas and efforts towards each species in the post-millennia period (2000-2017). We examined 145 reports and peer-reviewed articles, including species records and research types. Our analysis revealed that regardless that most of the bat research in the Philippines are directed towards surveys in a certain geographic area, which generally limited in species inventories. Numerous species remain understudied and taxonomically unresolved. While other aspect of bat research especially on bat ecology and ecosystem services are not well understood. Remarkably, there is a growing effort in bat conservation initiatives in the Philippines involving the academe, NGO’s, and conservationists aiming to protect threatened population and habitats.
Bat research efforts in the Philippines: a post-millennium review to identify future research prospects and priorities
Authors: Tanalgo Krizler C , Hughes Alice C
Published: January 2018

Empirical evidence is crucial to develop effective conservation policies. Documenting and assessing the status and threats towards a species and its habitat are essential steps towards developing appropriate policies to protect its population and mitigate existing threats to prevent future extinction. Here, we summarize recent bat research in the Philippines using a bibliographic approach to assess progress and gaps in different aspects of bat research species in a period of post-millennia to present. Overall, an average of 7.9 bat studies was reported per year including grey literature. Our analysis revealed that majority of bat studies conducted have been directed at community surveys (i.e., species inventories, rapid assessments). However, we found a disparity in terms of an average number of study per group; the “insectivorous bats” (6.15 study/yr) remain understudied compared to “fruit bats” (13.78 No study/year) for the past 18 years reflecting the lack of taxonomic studies in the country. While bat ecology research is still uncommon for most species. Interestingly, despite the lack of studies in many areas of bat research, there is a growing collaborative effort in bat conservation initiatives in the Philippines focused on the protection of many endemic and threatened species (e.g., flying foxes) and their habitats.
Exploring knowledge and attitudes toward non-communicable diseases among Village Health Teams in Eastern Uganda: a cross-sectional mixed methods study
Authors: Ojo Temitope , Hawley Nicola , Desai Mayur , Akiteng Ann , Guwatudde David , Schwartz Jeremy I
Published: January 2018

Background: Community health workers are essential personnel in resource-limited settings. In Uganda, they are organized into Village Health Teams (VHTs) and are focused on infectious diseases and maternal-child health; however, their skills could potentially be utilized in national efforts to reduce the growing burden of non-communicable diseases (NCDs). We sought to assess the knowledge of, and attitudes toward NCDs and NCD care among VHTs in Uganda as a step toward identifying their potential role in community NCD prevention and management. Methods: We administered a knowledge, attitudes and practices questionnaire to 68 VHT members from Iganga and Mayuge districts in Eastern Uganda. In addition, we conducted four focus group discussions with 33 VHT members. Discussions focused on NCD knowledge and facilitators of and barriers to incorporating NCD prevention and care into their role. A thematic qualitative analysis was conducted to identify salient themes in the data. Results: VHT members possessed some knowledge and awareness of NCDs but identified a lack of knowledge about NCDs in the communities they served. They were enthusiastic about incorporating NCD care into their role and thought that they could serve as effective conduits of knowledge about NCDs to their communities if empowered through NCD education, the availability of proper reporting and referral tools, and visible collaborations with medical personnel. The lack of financial remuneration for their role did not emerge as a major barrier to providing NCD services. Conclusions: Ugandan VHTs saw themselves as having the potential to play an important role in improving community awareness of NCDs as well as monitoring and referral of community members for NCD-related health issues. In order to accomplish this, they anticipated requiring context-specific and culturally adapted training as well as strong partnerships with facility-based medical personnel. A lack of financial incentivization was not identified to be a major a barrier to such role expansion. Developing a role for VHTs in NCD prevention and management should be a key consideration as local and national NCD initiatives are developed.
Tree size and relative clade age influence estimation of speciation rate shifts
Authors: Kodandaramaiah Ullasa , Murali Gopal
Published: January 2018

The development of methods to estimate rates of speciation and extinction from time-calibrated phylogenies has revolutionized evolutionary biology by allowing researchers to correlate diversification rate shifts with causal ecological factors. We use rigorous simulations to evaluate the statistical performance of three widely used modelling approaches - BiSSE, BAMM and MEDUSA - in relation to detection of speciation rates shifts. We simulated sets of trees with each tree having a single increase in speciation rate. We varied the location of shifts, the degree of increase in speciation rate and the total age of the tree. We then used BiSSE, BAMM and MEDUSA to estimate rate shifts. For BiSSE, we assigned different character states for the lineages with different simulated speciation rates. We show that all methods are better at detecting rate shifts when the change in speciation rate is higher, but had high Type II errors (non-detection of rate shifts). While the algorithms more accurately identified rate shifts close to the root of the tree, both perform poorly when the rate shift occurred more recently. All methods performed better with increase in the overall number of tips and the number of tips in the clade with rate shift, both of which are correlated with tree age and speciation rate asymmetry. We discuss the implications of this study for the use and development of methods for hypothesis testing based on diversification rate shifts.
Prevalence and temporal trends of overweight and obesity among children and adolescents in Jilin, Northeast China, 2011-2015
Authors: Li Yan , Li Zhijun , Sun Qing , Wang Mengying , Jiang Meng , Zhou Yutong , Wu Guanyu , Qi Yali
Published: January 2018

Objective: In China, the obesity epidemic is truly national and childhood obesity prevalence has rapidly increased and is close to the developed countries. This study aimed to estimate the prevalence and temporal trends of overweight and obesity among children and adolescents in Jilin City, China (2011-2015). Methods: The data derived from the census on students’ constitution and health in 2011-2015 carried out by the Jilin CDC, Jilin City. 191191 children and adolescents aged 7-18 years were included in the present survey, of which 37549 in 2011 to 41564 in the 2015. The newly developed age- and gender-specific BMI cutoffs by the working group on obesity in China were used to define overweight and obesity in children and adolescents. Results: The mean of BMI (body mass index) was significantly increasing from 20.9 kg/m2 in 2011 to 21.5 kg/m2 in 2015 in all subjects. Overweight and Obesity prevalence of total students aged 7-18 years had a significantly increasing from 2012 to 2015 (P<0.001), from 16.0% and 13.1% to 17.1% and 17.1%. The minimum value of BMI and overweight and obesity prevalence in overall age group all presented in 2012. Boys and girls all showed the significant increase in overweight and obesity prevalence in every age group from 2012 to 2015 and boys higher than girls (P<0.001). Regardless of girls and boys, the most likely of children and adolescents being overweight and obesity had been observed in the youngest age and lowest school grade category. Conclusion: In summary, our results indicate that all the overweight and obesity prevalence among children and adolescents over the past 5 years were higher than the 2010 Chinese National Level and Chinese large coastal cities’ level and a significantly increase from 2011-2015. Obesity epidemic is serious, at least not optimistic among children and adolescents in Jilin, Northeast China.
Optimizing taxonomic classification of marker gene sequences
Authors: Bokulich Nicholas A , Kaehler Benjamin D , Rideout Jai Ram , Dillon Matthew , Bolyen Evan , Knight Rob , Huttley Gavin A. , Caporaso J. Gregory
Published: January 2018

Background. Taxonomic classification of marker-gene sequences is an important step in microbiome analysis.

Results. We present q2-feature-classifier (https://github.com/qiime2/q2-feature-classifier), a QIIME 2 plugin containing several novel machine-learning and alignment-based taxonomy classifiers that meet or exceed classification accuracy of existing methods. We evaluated and optimized several commonly used taxonomic classification methods (RDP, BLAST, BLAST+, UCLUST) and several new methods (a scikit-learn naive Bayes machine-learning classifier, and VSEARCH and SortMeRNA alignment-based methods).

Conclusions. Our results illustrate the importance of parameter tuning for optimizing classifier performance, and we make explicit recommendations regarding parameter choices for a range of standard operating conditions. q2-feature-classifier and our evaluation framework, tax-credit, are both free, open-source, BSD-licensed packages available on GitHub.
Pathogenic amino acids in mitochondrial proteins more frequently arise in lineages closely related to human than in distant lineages
Authors: Klink Galya V , Bazykin Georgii A. , Golovin Andrey V.
Published: January 2018

Propensities for different amino acids within a protein site change in the course of evolution, so that an amino acid deleterious in a particular species may be acceptable at the same site in a different species. Here, we study the amino acid-changing variants in human mitochondrial genes, and analyze their occurrence in non-human species. We show that substitutions giving rise to the human amino acid variant tend to occur in lineages closely related to human more frequently than in more distantly related lineages, indicating that a human variant is more likely to be deleterious in more distant species. Unexpectedly, amino acids corresponding to pathogenic alleles in humans also more frequently originate at more closely related lineages. Therefore, a pathogenic variant still tends to be more acceptable in human mitochondria than a variant that may only be fit after a substantial perturbation of the protein structure.
Pathogenic amino acids in mitochondrial proteins more frequently arise in lineages closely related to human than in distant lineages
Authors: Klink Galya V , Golovin Andrey V. , Bazykin Georgii A.
Published: January 2018

Propensities for different amino acids within a protein site change in the course of evolution, so that an amino acid deleterious in a particular species may be acceptable at the same site in a different species. Here, we study the amino acid-changing variants in human mitochondrial genes, and analyze their occurrence in non-human species. We show that substitutions giving rise to the human amino acid variant tend to occur in lineages closely related to human more frequently than in more distantly related lineages, indicating that a human variant is more likely to be deleterious in more distant species. Unexpectedly, amino acids corresponding to pathogenic alleles in humans also more frequently originate at more closely related lineages. Therefore, a pathogenic variant still tends to be more acceptable in human mitochondria than a variant that may only be fit after a substantial perturbation of the protein structure.
Glide analysis and bone strength tests indicate powered flight capabilities in hatchling pterosaurs
Authors: Witton Mark P , Martin-Silverstone Elizabeth , Naish Darren
Published: January 2018

Pterosaur embryos and ‘hatchling’ specimens show a surprising level of skeletal development including well-ossified skeletons and large wings. This has prompted interpretations of pterosaurs as being flight-capable from the earliest ontogenetic stages, contrasting them against the majority of other flying animals, living or extinct. Though popular, this hypothesis is not universally accepted. Some authors propose that pterosaurs only became flight capable once they reached 50% of maximum size, explaining a slowing of growth rate in later ontogeny as metabolic resources were diverted into an energy-demanding form of locomotion. We investigated these hypotheses through glide performance and wing bone strength analysis on hatchling-grade specimens of two pterosaurs, Pterodaustro guinazui and Sinopterus dongi. We found that hatchling pterosaurs were excellent gliders, but with a wing ecomorphology more comparable to powered fliers than obligate gliders. Bone strength analysis shows that hatchling pterosaur wing bones are structurally identical to those of larger pterosaurs and – because of their very low body masses – their bending strength relative to body weight is very high, comparable to or exceeding the greatest values estimated for larger, more mature pterosaurs. Hatchling pterosaurs are thus as mechanically adapted to powered flight stresses as other pterosaurs, if not moreso. Together with our glide tests, this result supports interpretations of hatchling pterosaurs as flight-capable. Size differences between pterosaur hatchlings and larger members of their species dictate differences in wing ecomorphology and flight capabilities at different life stages, which might have bearing on pterosaur ontogenetic niching.
Whole genome sequencing of Rhodotorula mucilaginosa isolated from the chewing stick (Distemonanthus benthamianus): insights into Rhodotorula phylogeny, mitogenome dynamics and carotenoid biosynthesis
Authors: Gan Han Ming , Thomas Bolaji N , Cavanaguh Nicole T , Morales Grace H , Mayers Ashley N , Savka Michael A , Hudson Andre O
Published: January 2018

In industry, the yeast Rhodotorula mucilaginosa is commonly used for the production of carotenoids. The production of carotenoids is important because they are used as natural colorants in food and some carotenoids are precursors of retinol (vitamin A). However, the identification and molecular characterization of the carotenoid pathway/s in species belonging to the genus Rhodotorula is scarce due to the lack of genomic information thus potentially impeding effective metabolic engineering of these yeast strains for improved carotenoid production. In this study, we report the isolation, identification, characterization and the whole nuclear genome and mitogenome sequence of the endophyte R. mucilaginosa RIT389 isolated from Distemonanthus benthamianus, a plant known for its anti-fungal and antibacterial properties and commonly used as chewing sticks. The assembled genome of R. mucilaginosa RIT389 is 19 Mbp in length with an estimated genomic heterozygosity of 9.29%. Whole genome phylogeny supports the species designation of strain RIT389 within the genus in addition to validating the monophyly of the genus Rhodotorula. Further, we report for the first time, the recovery of the complete mitochondrial genome of R. mucilaginosa using the genome skimming approach. The assembled mitogenome is at least 7,000 bases larger than that of Rhodotorula taiwanensis which is largely attributed to the presence of large intronic regions containing open reading frames coding for homing endonuclease from the LAGLIDADG and GIY-YIG families. Furthermore, genomic regions containing the key genes for carotenoid production were identified in R. mucilaginosa RIT389, revealing differences in gene synteny that may play a role in the regulation of the biotechnologically important carotenoid synthesis pathways in yeasts.
Genome rearrangements and phylogeny reconstruction in Yersinia pestis
Authors: Bochkareva Olga O , Dranenko Natalia O , Ocheredko Elena S , Kanevsky German M , Lozinsky Yaroslav N , Khalaycheva Vera A , Artamonova Irena I , Gelfand Mikhail S
Published: January 2018

Genome rearrangements have played an important role in the evolution of Yersinia pestis from its progenitor Yersinia pseudotuberculosis. Traditional phylogenetic trees for Y. pestis based on sequence comparison have short internal branches and low bootstrap supports as only a small number of nucleotide substitutions have occurred. On the other hand, even a small number of genome rearrangements may resolve topological ambiguities in a phylogenetic tree.

We reconstructed the evolutionary history of genome rearrangements in Y. pestis. We also reconciled phylogenetic trees for each of the three CRISPR-loci to obtain an integrated scenario of the CRISPR-cassette evolution. We detected numerous parallel inversions and gain/loss events by the analysis of contradictions between the obtained evolutionary trees. We also tested the hypotheses that large within-replichore inversions tend to be balanced by subsequent reversal events and that the core genes less frequently switch the chain by inversions. Both predictions were not confirmed.

Our data indicate that an integrated analysis of sequence-based and inversion-based trees enhances the resolution of phylogenetic reconstruction. In contrast, reconstructions of strain relationships based on solely CRISPR loci may not be reliable, as the history is obscured by large deletions, obliterating the order of spacer gains. Similarly, numerous parallel gene losses preclude reconstruction of phylogeny based on gene content.
From trash to treasure: detecting unexpected contamination in unmapped NGS data
Authors: Granata llaria , Sangiovanni Mara , Thind Amarinder Singh , Guarracino Mario Rosario
Published: January 2018

Standard procedures for NGS data analysis involve a pre-processing step of reads quality assessment, followed by the alignment of the filtered reads to a reference genome. Typically the amount of reads that correctly maps to the specific reference genome ranges between 70% and 90%, leaving in some cases a consistent fraction of unmapped sequences. Investigating the reasons of this discrepancy may provide relevant information about the source of the so called unmapped reads. It is not unusual that genetic material of microorganisms is present in biological samples undergoing sequencing. These exogenous sequences can derive from the normal or altered tissues microbiome (upstream contamination) or from a contamination occurring during the samples processing (downstream contamination).

Here we propose DecontaMiner, a tool to unravel the presence of contaminating sequences among the unmapped reads. It uses a subtraction approach in which the sequences are first filtered according to quality parameters and then mapped to ribosomal, mithocondrial and foreign organism's databases. The reads that do not map on human genome are then mapped, through a local alignment algorithm (MegaBlast), to bacteria, fungi and viruses genome. DecontaMiner generates several output files to track all the processed reads, and to provide a complete report of their characteristics. The good quality matches on microorganism genomes are counted and compared among samples. The main novelty of DecontaMiner is the versatility of its use together with a complete, easy to use, and automatic pipeline.

DecontaMiner has been mainly used to detect contamination in human RNA-seq data, but the pipeline can be easily tailored using the configuration files and flags to process DNA-seq data, and unmapped data coming from non-human species.
Origin of a folded protein from an intrinsically disordered ancestral peptide
Authors: Zhu Hongbo , Sepulveda Edgardo , Hartmann Marcus D , Kogenaru Manjunatha , Martin Jörg , Lupas Andrei N
Published: January 2018

Contemporary proteins can be traced back to a basic set of a few thousand domain prototypes. The origin of these domain prototypes, however, remains poorly understood. We have proposed that they arose from an ancestral set of peptides, which acted as cofactors of RNA-mediated catalysis and replication. Their ability to fold was an emergent property of peptide-RNA coevolution. The ribosome is the main survivor of this primordial RNA world and offers an excellent model system for retracing the steps that led to the folded proteins of today. We have retraced this emancipation from the RNA scaffold computationally and experimentally, by investigating the plausible ancestor in ribosomal proteins for a cytosolic protein fold, the tetratricopeptide repeat (TPR). The repeat units of the fold are helical hairpins. These αα-hairpins in all known TPR-containing proteins can be detected using a single sequence profile, underscoring their homologous origin. More importantly, the αα-hairpin has been discovered to occur in multiple seemingly unrelated protein folds. Through the sequence and structure comparison of the TPR αα-hairpins to all proteins of known structure, we detected several potential homologs in non-repetitive proteins, including one from a ribosomal protein S20 (RPS20). Subsequently, by amplifying an αα-hairpin from a RPS20, which is unstructured in the absence of the cognate ribosomal RNA, we explored whether an intrinsically disordered peptide could form a folded protein through an increase in complexity afforded by repetition. Simple repetition was not sufficient in our case, but the repeat protein was so close to a folded structure that only two point mutations per repeat were necessary to allow it to fold reliably. The mutations needed for this transition did not appear to affect negatively the interaction with the RNA scaffold and were neutral for survival and growth in the parent organism, raising the possibility that they could have been among the variants sampled multiply in the course of evolution. TPRs could thus have plausibly arisen by amplification from an ancestral, RNA-dependent helical hairpin, as proposed by our theory.
The first virtual cranial endocast of a porolepiform fish and the evolution of the Dipnomorpha
Authors: Henderson Struan , Challands Tom , Giles Sam , den Blaauwen Jan
Published: January 2018

The Dipnomorpha include the extinct Porolepiformes, in addition to Powichthys and Youngolepis and the extant Dipnoi (lungfish). As sister group to the Tetrapodomorpha, the Dipnomorpha hold a valuable place in our understanding of early sarcopterygian evolution. With complete cranial endocasts now known from most other stem sarcopterygian groups including actinistians and tetrapodomorphs (which bracket the Dipnomorpha), a thorough understanding of the porolepiform endocranium remains one of the last pieces in the puzzle towards understanding evolution of the neurocranium in stem sarcopterygians.

We present the first virtual cranial endocast of a porolepiform fish (Glyptolepis paucidens) demonstrating that it displays predominantly primitive sarcopterygian endocast characters including: lack of a bifurcation of the olfactory nerves, separate pineal and parapineal recesses, circumvention of the nasal capsule by the profundus nerve, and sessile olfactory bulbs. The union of the orbitonasal canal and the nasal capsule is consistent with that seen in Powichthys, Youngolepis and other porolepiforms, however circumvention of the nasal capsule by the profundus resembles the dipnoan Dipterus, contrasting the state observed in other porolepiforms and Powichthys.

Inconsistent with the general primitive nature of the endocast seen in Glyptolepis is the large, curved hypophyseal recess, a feature shared with Powicthys but unlike Youngolepis. Furthermore, Glyptolepis displays ventral expansion of the telencephalon - a character thought to be derived within the Dipnoi.

This new data enhances our understanding of brain and sensory evolution in sarcopterygians. In particular, it shows conservatism in stem Porolepiformes contrary to the disparate morphology of their sister-group the Dipnoi.
Loss of microbiota depletes cross-reactive Foxp3+ Tregs leading to selective immunopathologies
Authors: Kamala Tirumalai , Usharauli David
Published: January 2018

The 'Hygiene hypothesis', a cornerstone model to account for the role of exogenous pathogens and later of endogenous microbiota in immune disorders, is currently presumed to operate at the innate immunity and metabolite levels to properly 'educate' the immune system. Doing so however fails to satisfactorily account for the antigen-specific nature of such disorders. SPIRAL is a novel interpretive framework that resolves this dilemma. It represents the periodic table of cross-reactive Foxp3+ regulatory T cell (Treg) epitopes selected from commensal microbiota over evolutionary time to mediate self-nonself discrimination and effector class regulation. Here, we utilize the SPIRAL's predictive power to provide a mechanistic antigen-specific basis for the initiation of allergies and autoimmune diseases as well as for the failure to mount effective anti-tumor and vaccine responses through selective loss of microbiota and corresponding cross-reactive Foxp3+ Tregs.
Multi-resolution network modelling of T-cells for precision medicine of multiple sclerosis
Authors: Gustafsson Mika
Published: January 2018

Background: Due to the interplay between many factors, systems medicine of complex diseases is most often centered either on individual genes, or on statistical associations. Complex network analysis could potentially explain systems-wide differences between patients and controls. In order to achieve this understanding using incomplete existing data, we need these powerful coarse-graining procedures. First, disease genes have been shown to co-localise for many complex diseases in protein-interaction networks, and thereby forming disease modules, however the identification of such modules is not well-defined (Gustafsson Genome Medicine 2014). We have developed ModifieR, an R-package which combines 10 existing and new methods using statistical overlaps between multiple omics as a guiding principle. Second, upstream hub transcription factors (TFs) regulating those modules have shown to be good candidates for early predictive medicine (Gustafsson Science Transl Med 2015). Third, those TFs tend to be interconnected and form core circuits, which have a great genome-wide impact, and could be modelled by our recent dynamic ordinary differential equation based modelling tool, LASSIM (Magnusson, PLoS Comput Biol 2017, https://gitlab.com/Gustafsson-lab/ ). Each of these concepts could synergistically increase the analysis resolution. A critical problem is that parts of the models are patient-specific while parts are highly conserved across patients, which we work to resolve.

Methods: A key feature to estimate patient specific disease-relevant networks is multiple time-points omics in cells reflecting different disease-relevant stages. We hypothesise that by connecting patients at multiple stages we can infer the disease-relevant patient specific gene regulatory networks, from which we can draw statistical conclusions (extension of the work in Hellberg Cell Reports 2016). For this purpose, we are performing modelling of CD4+ T-cells in multiple sclerosis using generally applicable principles in open access pipelines. Briefly, we apply a linear transcription factor-target model based on eQTL-targeted sequencing and patients in two time-points. The model uses L1 constraints, similar to our previous models (Gustafsson Science Transl Medicine 2015, Gustafsson IEEE 2005), but is allowed to infer transcription factor activity based on target gene expression, using the CVX optimisation toolbox.

Results: We found that the inferred patient specific GRN models with L1 constraint predicted 50% of the transcriptomic changes using cross-validation. Generally, we found that the TF activity poorly correlated with its mRNA level. Moreover, we found TFs with a significantly higher effect in patients than controls.

Discussion: My research focus on three recent network medicine concepts that enable a gradually increased resolution of modelling for complex diseases, which I ultimately aim at integrating in a unifying precisions medicine toolbox.
Transparent PET optical window for microfluidic cell culture device
Authors: Ng Wenfa
Published: January 2018

Microfluidic cell culture chambers have enabled the isolation, culture and growth of various species of microorganisms and human cells. However, based on elastomers such as poly(dimethyl siloxane) (PDMS), these culture devices are not readily amenable to imaging or spectroscopy in the optical and infrared spectrum. Specifically, while PDMS is optically transparent, significant diffraction and reflection of light waves through the material does not endow it for use with various modes of spectroscopy where real-time imaging applications have been developed. For example, optical or infrared spectroscopy of the microfluidic device, through an optically transparent window, could provide readout of the types and concentration of fluorescent reporters within the growth chamber, which are usually correlated with gene expression or molecular binding events. Thus, there is a need for an optically transparent window for microfluidic cell culture device with the necessary mechanical strength, and which enables both optical and infrared imaging and spectroscopy to be performed. To this end, a flexible optically transparent polymer, poly(ethylene terephthalate), PET, could serve as the optical window of a microfluidic cell culture device. Given its optical transparency and flexibility, the PET thin film could be layered on an imaging area of a PDMS microfluidic device, that allows for optical and infrared imaging and spectroscopy. Thus, using readily available PET thin film, an optically transparent window could be placed on a PDMS microfluidic growth chamber for imaging or spectroscopy in the optical and infrared spectrum. Interested researchers may want to expand on the idea presented here.
Linear Approximation Analysis: an improved technique for linear cryptanalysis of 4-bit Bijective Crypto S-Boxes
Authors: Dey Sankhanil , Ghosh Ranjan
Published: January 2018

4-bit Linear Relations play an important role in Cryptanalysis of 4-bit Bijective S-Boxes. Count of existence of all 4-bit Linear Relations, for all of 16 input and output 4-bit bit patterns of 4-bit Bijective S-Boxes said as S-Boxes has been reported in Linear Cryptanalysis of 4-bit S-Boxes. In this paper a brief review of this cryptanalytic method for 4-bit S-Boxes has been introduced in a very lucid and conceptual manner. A new Analysis to search for the existing Linear Approximations among the input Boolean Functions (BFs) and output BFs of a particular 4-bit S-Box has also been introduced in this paper. The search is limited to find the existing Linear Relations or Approximations in the contrary to count the number existence among all 16 4-bit input and output bit patterns for all possible linear approximations.
Enumerating common molecular substructures
Authors: Engler Martin S , El-Kebir Mohammed , Mulder Jelmer , Mark Alan E , Geerke Daan P , Klau Gunnar W
Published: January 2018

Finding and enumerating common molecular substructures is an important task in cheminformatics, where small molecules are often modeled as molecular graphs. We introduce the problem of enumerating all maximal k-common molecular fragments of a pair of molecular graphs. A k-common fragment is a common connected induced subgraph that consists of a common core and a common k-neighborhood. It is thus a generalization of the NP-hard task to enumerate all maximal common connected induced subgraphs (MCCIS) of two graphs, which corresponds to the k = 0 case.

We extend the MCCIS enumeration algorithm by Ina Koch and apply algorithm engineering techniques to solve practical instances fast for the general k > 0 case, which is relevant, for example, for automatically generating force field topologies for molecular dynamics (MD) simulations. We find that our methods achieve good performance on a real-world benchmark of all-against-all comparisons of 255 molecules.

Our software is available under the LGPL open source license at https://github.com/enitram/mogli .
The proteomic response of the reef coral Pocillopora acuta to experimentally elevated temperatures
Authors: Mayfield Anderson B , Chen Yi-Jyun , Lu Chi-Yu , Chen Chii-Shiarng
Published: January 2018

Although most reef-building corals live near the upper threshold of their thermotolerance, some scleractinians are resilient to temperature increases. For instance, Pocillopora acuta specimens from an upwelling habitat in Southern Taiwan survived a 9-month experimental exposure to 30°C, a temperature hypothesized to induce stress. To gain a greater understanding of the molecular pathways underlying such high-temperature acclimation, the protein profiles of experimental controls incubated at 27°C were compared to those of conspecific P. acuta specimens exposed to 30°C for two, four, or eight weeks, and differentially expressed proteins (DEPs) were removed from the protein gels and sequenced with mass spectrometry. Sixty unique DEPs were uncovered across both eukaryotic compartments of the P. acuta-dinoflagellate (genus Symbiodinium) mutualism, and Symbiodinium were more likely to up-regulate protein expression in response to high temperature exposure than the coral hosts in which they resided at the 2-week sampling time. Furthermore, different cellular pathways were affected by elevated temperature exposure in each compartment; Symbiodinium tended to up-regulate the expression of proteins involved in the cellular stress response, whereas the differentially expressed host coral proteome featured numerous proteins involved in cytoskeletal structure, immunity, and metabolism. These proteome-scale data suggest that the coral host and its intracellular dinoflagellates have differing cellular strategies for acclimating to elevated temperatures.
Determinants of antimicrobial use practices among veterinary clinicians at The University of Tennessee Veterinary Medical Center
Authors: Ekakoro John Eddie , Okafor Chika C
Published: January 2018

Background. Antimicrobial drugs in veterinary medical practice are primarily prescribed for the purposes of maintaining or improving health and increasing productivity. However, their value is being eroded by antimicrobial resistance (AMR). Indiscriminate use of antimicrobial drugs is suggested as one of the modifiable factors contributing to the development of AMR. To reduce indiscriminate use and to improve antimicrobial use, veterinary practices are encouraged to adopt good stewardship practices. Therefore, the objectives of this study were: to identify factors influencing clinician decisions to begin using antimicrobials as well as the choice of antimicrobials used at The University of Tennessee Veterinary Medical Center (UTVMC); to evaluate the practices, perceptions, opinions and concerns of veterinary clinicians at UTVMC concerning antimicrobial use, antimicrobial stewardship, and AMR.

Methods. This study’s protocol was approved by the University of Tennessee Knoxville IRB for the Protection of Human Subjects in Research. Survey software was used to send a questionnaire to 121 eligible participants, where all were UTVMC faculty with clinical appointments and house officers. Cumulative logit models were fitted to investigate associations between categorical explanatory variables and ordinal response variables.

Results. A response rate of 51.24% was achieved. Of the 62 respondents, 47 (75.81%) reported that bacteriological culture and antimicrobial susceptibility test results were extremely important in their antimicrobial prescription decision-making. Thirty-two (51.61%) respondents believed antimicrobials are being over-prescribed. The cephalosporin class was the most preferred antimicrobial class, while the lincosamide class was the least preferred. From the multivariable cumulative logit model, year of graduation from veterinary school (P = 0.034) and clinicians’ primary patient load (P = 0.009) were significantly associated with clinicians’ degree of concern about AMR.

Conclusions and clinical relevance. The findings suggest a need for more awareness about AMR among veterinary clinicians. Improvements in antimicrobial stewardship are needed, especially among veterinary clinicians who graduated after 1999. Educational practices that target modification of antimicrobial prescription practices of veterinary clinicians would likely improve a Good Stewardship Practice (GSP) mindset. GSP is important in prolonging the efficacy of currently available antimicrobial drugs.
Founder effects drive the genetic structure of passively dispersed aquatic invertebrates
Authors: Montero-Pau Javier , Gomez Africa , Serra Manuel
Published: January 2018

Populations of passively dispersed organisms in continental aquatic habitats typically show high levels of neutral genetic differentiation, despite their high dispersal capabilities. Several evolutionary factors, including founder events and local adaptation, and life cycle features such as high population growth rates and the presence of propagule banks, have been proposed to be responsible for this paradox. Here, we have modeled the colonization process in these organisms to assess the impact of migration rate, growth rate, population size, local adaptation and life-cycle features on their population genetic structure. Our simulation results show that the strongest effect on population structure is caused by persistent founder effects, resulting from the interaction of a few population founders, high population growth rates, large population sizes and the presence of diapausing egg banks. In contrast, the role of local adaptation, genetic hitchhiking and migration is limited to small populations in these organisms. Our results indicate that local adaptation could have different impact on genetic structure in different groups of zooplankters.
Interoperability of RehabRobo-Onto
Authors: Dogmus Zeynep , Patoglu Volkan , Erdem Esra
Published: January 2018

The leading cause of permanent disability in developed countries is due to neurological injuries, such as stroke. While physical rehabilitation therapy is indispensable for treating neurological disabilities, repetitive and high intensity therapies place high physical burden on the therapist and significantly increase the cost of such treatments. These challenges have led to design and development of various robot-assisted rehabilitation devices.

As the number of rehabilitation robots increase, the information about them also increases, but most of the time in unstructured forms (e.g., as text in publications), which make it harder to access the requested knowledge and reason about it. Also, due to interdisciplinary nature of rehabilitation robotics, sometimes requested knowledge requires integration of further knowledge from related disciplines (e.g., physical medicine). Motivated by these challenges, we have designed and developed the first formal rehabilitation robotics ontology, called RehabRobo-Onto, to represent knowledge about rehabilitation robotics in the structured form of OWL.

In this abstract, we continue our studies on RehabRobo-Onto by discussing its interoperability with the available knowledge resources, such as Foundational Model of Anatomy (FMA) and Human Disease Ontology (DO), towards personalized physical rehabilitation therapies.
Weighted growth functions of automatic groups
Authors: Vejdemo-Johansson Mikael
Published: January 2018

The growth function is the generating function for sizes of spheres around the identity in Cayley graphs of groups. We present a novel method to calculate growth functions for automatic groups with normal form recognizing automata that recognize a single normal form for each group element, and are at most context free in complexity: context free grammars can be translated into algebraic systems of equations, whose solutions represent generating functions of their corresponding non-terminal symbols.

This approach allows us to seamlessly introduce weightings on the growth function: assign different or even distinct weights to each of the generators in an underlying presentation, such that this weighting is reflected in the growth function. We recover known growth functions for small braid groups, and calculate growth functions that weight each generator in an automatic presentation of the braid groups according to their lengths in braid generators.