bluuebunny/crossref_metadata_2025_split huggingface dataset:
MOLI: Multi-Omics Late Integration with deep neural networks for drug response prediction
Authors: Sharifi-Noghabi Hossein , Zolotareva Olga , Collins Colin C. , Ester Martin 
Published: January 2019

AbstractMotivationHistorically, gene expression has been shown to be the most informative data for drug response prediction. Recent evidence suggests that integrating additional omics can improve the prediction accuracy which raises the question of how to integrate the additional omics. Regardless of the integration strategy, clinical utility and translatability are crucial. Thus, we reasoned a multi-omics approach combined with clinical datasets would improve drug response prediction and clinical relevance.ResultsWe propose MOLI, a Multi-Omics Late Integration method based on deep neural networks. MOLI takes somatic mutation, copy number aberration, and gene expression data as input, and integrates them for drug response prediction. MOLI uses type-specific encoding subnetworks to learn features for each omics type, concatenates them into one representation and optimizes this representation via a combined cost function consisting of a triplet loss and a binary cross-entropy loss. The former makes the representations of responder samples more similar to each and different from the non-responders, and the latter makes this representation predictive of the response values. We validate MOLI on in vitro and in vivo datasets for five chemotherapy agents and two targeted therapeutics. Compared to state-of-the-art single-omics and early integration multi-omics methods, MOLI achieves higher prediction accuracy in external validations. Moreover, a significant improvement in MOLI’s performance is observed for targeted drugs when training on a pan-drug input, i.e. using all the drugs with the same target compared to training only on drug-specific inputs. MOLI’s high predictive power suggests it may have utility in precision oncology.Availability of the implemented codeshttps://github.com/hosseinshn/MOLIContactccollins@prostatecentre.com and ester@cs.sfu.ca
Comparative Transcriptomic Signature of the Simulated Microgravity Response inCaenorhabditis elegans
Authors: Çelen İrem , Jayasinghe Aroshan , Doh Jung H. , Sabanayagam Chandran R. 
Published: January 2019

AbstractBackgroundGiven the growing interest in human exploration of space, it is crucial to identify the effect of space conditions on biological processes. The International Space Station (ISS) greatly helps researchers determine these effects. However, the impact of the ISS-introduced potential confounders (e.g., the combination of radiation and microgravity exposures) on the biological processes are often neglected, and separate investigations are needed to uncover the impact of individual conditions.ResultsHere, we analyze the transcriptomic response ofCaenorhabditis elegansto simulated microgravity and observe the maintained transcriptomic response after return to ground conditions for four, eight, and twelve days. Through the integration of our data with those in NASA GeneLab, we identify the gravitome, which we define as microgravity-responsive transcriptomic signatures. We show that 75% of the simulated microgravity-induced changes on gene expression persist after return to ground conditions for four days while most of these changes are reverted after twelve days return to ground conditions. Our results from integrative RNA-seq and mass spectrometry analyses suggest that simulated microgravity affects longevity regulating insulin/IGF-1 and sphingolipid signaling pathways.ConclusionsOur results address the sole impact of simulated microgravity on transcriptome by controlling for the other space-introduced conditions and utilizing RNA-seq. Using an integrative approach, we identify a conserved transcriptomic signature to microgravity and its sustained impact after return to the ground. Moreover, we present the effect of simulated microgravity on distinct ceramide profiles. Overall, this work can provide insights into the sole effect of microgravity on biological systems.
Is removal of weak connections necessary for graph-theoretical analysis of dense weighted structural connectomes?
Authors: Civier Oren , Smith Robert Elton , Yeh Chun-Hung , Connelly Alan , Calamante Fernando 
Published: January 2019

ABSTRACTRecent advances in diffusion MRI tractography permit the generation of dense weighted structural connectomes that offer greater insight into brain organization. However, these efforts are hampered by the lack of consensus on how to extract topological measures from the resulting graphs. Here we evaluate the common practice of removing the graphs’ weak connections, which is primarily intended to eliminate spurious connections and emphasize strong connections. Because this processing step requires arbitrary or heuristic-based choices (e.g., setting a threshold level below which connections are removed), and such choices might complicate statistical analysis and inter-study comparisons, in this work we test whether removing weak connections is indeed necessary. To this end, we systematically evaluated the effect of removing weak connections on a range of popular graph-theoretical metrics. Specifically, we investigated if (and at what extent) removal of weak connections introduces a statistically significant difference between two otherwise equal groups of healthy subjects when only applied to one of the groups. Using data from the Human Connectome Project, we found that removal of weak connections had no statistical effect even when removing the weakest~70-90% connections. Removing yet a larger extent of weak connections, thus reducing connectivity density even further, did produce a predictably significant effect. However, metric values became sensitive to the exact connectivity density, which has ramifications regarding the stability of the statistical analysis. This pattern persisted whether connections were removed by connection strength threshold or connectivity density, and for connectomes generated using parcellations at different resolutions. Finally, we showed that the same pattern also applies for data from a clinical-grade MRI scanner. In conclusion, our analysis revealed that removing weak connections is not necessary for graph-theoretical analysis of dense weighted connectomes. Because removal of weak connections provides no practical utility to offset the undesirable requirement for arbitrary or heuristic-based choices, we recommend that this step is avoided in future studies.Declarations of interestnone.
Analysis ofBrevundimonas subvibrioidesdevelopmental signaling systems reveals unexpected differences between phenotypes and c-di-GMP levels
Authors: Sperling Lauryn , Kaever Volkhard , Curtis Patrick D. 
Published: January 2019

AbstractThe DivJ-DivK-PleC signaling system ofCaulobacter crescentusis a signaling network that regulates polar development and the cell cycle. This system is conserved in related bacteria, including the sister genusBrevundimonas. Previous studies had shown unexpected phenotypic differences between theC. crescentus divKmutant and the analogous mutant ofBrevundimonas subvibrioides, but further characterization was not performed. Here, phenotypic assays analyzing motility, adhesion, and pilus production (the latter characterized by a newly discovered bacteriophage) revealed thatdivJandpleCmutants have mostly similar phenotypes as theirC. crescentushomologs, butdivKmutants maintain largely opposite phenotypes than expected. Suppressor mutations of theB. subvibrioides divKmotility defect were involved in cyclic-di-GMP (c-di-GMP) signaling, including the diguanylate cyclasedgcB, andcleDwhich is hypothesized to affect flagellar function in a c-di-GMP dependent fashion. However, the screen did not identify the diguanylate cyclasepleD.Disruption ofpleDinB. subvibrioidescaused hypermotility in wild-type, but not in thedivKbackground. Analysis of c-di-GMP levels in these strains revealed incongruities between c-di-GMP levels and displayed phenotypes with a notable result that suppressor mutations altered phenotypes but had little impact on c-di-GMP levels in thedivKbackground. Conversely, when c-di-GMP levels were artificially manipulated, alterations of c-di-GMP levels in thedivKstrain had minimal impact on phenotypes. These results suggest that DivK performs a critical function in the integration of c-di-GMP signaling into theB. subvibrioidescell cycle.ImportanceCyclic-di-GMP signaling is one of the most broadly conserved signaling systems in bacteria, but there is little understanding of how this system directly affects the physiology of the organism. InC. crescentus, c-di-GMP has been integrated into the developmental cell cycle, but there is increasing evidence that environmental factors can impact this system as well. The research presented here suggests that developmental signaling could impact physiological Processes in c-di-GMP dependent and independent ways. This hints that the integration of these signaling networks could be more complex than previously hypothesized, which could have a bearing on the larger field of c-di-GMP signaling. In addition, this work further examines how much models developed in one organism can be extrapolated to related organisms.
Bacteriophage resistance alters antibiotic mediated intestinal expansion of enterococci
Authors: Chatterjee Anushila , Johnson Cydney N. , Luong Phat , Hullahalli Karthik , McBride Sara W. , Schubert Alyxandria M. , Palmer Kelli L. , Carlson Paul E. , Duerkop Breck A. 
Published: January 2019

AbstractEnterococcus faecalisis a human intestinal pathobiont with intrinsic and acquired resistance to many antibiotics, including vancomycin. Nature provides a diverse and virtually untapped repertoire of bacterial viruses, or bacteriophages (phages), that could be harnessed to combat multi-drug resistant enterococcal infections. Bacterial phage resistance represents a potential barrier to the implementation of phage therapy, emphasizing the importance of investigating the molecular mechanisms underlying the emergence of phage resistance. Using a cohort of 19 environmental lytic phages with tropism againstE. faecalis, we found that these phages require the enterococcal polysaccharide antigen (Epa) for productive infection. Epa is a surface-exposed heteroglycan synthesized by enzymes encoded by both conserved and strain specific genes. We discovered that exposure to phage selective pressure favors mutation in non-conservedepagenes both in culture and in a mouse model of intestinal colonization. Despite gaining phage resistance,epamutant strains exhibited a loss of resistance to the cell wall targeting antibiotics, vancomycin and daptomycin. Finally, we show that anE. faecalis epamutant strain is deficient in intestinal colonization, cannot expand its population upon antibiotic-driven intestinal dysbiosis and fails to be efficiently transmitted to juvenile mice following birth. This study demonstrates that phage therapy could be used in combination with antibiotics to target enterococci within a dysbiotic microbiota. Enterococci that evade phage therapy by developing resistance may be less fit at colonizing the intestine and sensitized to vancomycin preventing their overgrowth during antibiotic treatment.
Diversity matters: Deep-sea mussels harbor multiple symbiont strains
Authors: Ansorge Rebecca , Romano Stefano , Sayavedra Lizbeth , Kupczok Anne , Tegetmeyer Halina E. , Dubilier Nicole , Petersen Jillian 
Published: January 2019

AbstractGenetic diversity of closely-related free-living microbes is widespread and underpins ecosystem functioning, but most evolutionary theories predict that it destabilizes intimate mutualisms. Indeed, symbiont strain diversity has long assumed to be restricted in intracellular bacteria associated with animals. Here, we sequenced the metagenomes and metatranscriptomes of 18Bathymodiolusmussel individuals from four species, covering their known distribution range at deep-sea hydrothermal vents in the Atlantic. We show that as many as 16 strains of intracellular, sulfur-oxidizing symbionts coexist in individualBathymodiolusmussels. Co-occurring symbiont strains differed extensively in key metabolic functions, such as the use of energy and nutrient sources, electron acceptors and viral defense mechanisms. Most strain-specific genes were expressed, highlighting their adaptive potential. We show that fine-scale diversity is pervasive inBathymodiolussymbionts, and hypothesize that it may be widespread in low-cost symbioses where the environment, not the host, feeds the symbionts.
Same-Species Contamination Detection with Variant Calling Information from Next Generation Sequencing
Authors: Jiang Tao , Buchkovich Martin , Motsinger-Reif Alison 
Published: January 2019

AbstractMotivationSame-species contamination detection is an important quality control step in genetic data analysis. Compared with widely discussed cross-species contamination, same-species contamination is more challenging to detect, and there is a scarcity of methods to detect and correct for this quality control issue. Same-species contamination may be due to contamination by lab technicians or samples from other contributors. Here, we introduce a novel machine learning algorithm to detect same species contamination in next generation sequence data using support vector machines. Our approach uniquely detects such contamination using variant calling information stored in the variant call format (VCF) files (either DNA or RNA), and importantly can differentiate between same species contamination and mixtures of tumor and normal cells.MethodsIn the first stage of our approach, a change-point detection method is used to identify copy number variations or copy number aberrations (CNVs or CNAs) for filtering prior to testing for contamination. Next, single nucleotide polymorphism (SNP) data is used to test for same species contamination using a support vector machine model. Based on the assumption that alternative allele frequencies in next generation sequencing follow the beta-binomial distribution, the deviation parameter ρ is estimated by maximum likelihood method. All features of a radial basis function (RBF) kernel support vector machine (SVM) are generated using either publicly available or private training data. Lastly, the generated SVM is applied in the test data to detect contamination. If training data is not available, a default RBF kernel SVM model is used.ResultsWe demonstrate the potential of our approach using simulation experiments, creating datasets with varying levels of contamination. The datasets combine, in silico, exome sequencing data of DNA from two lymphoblastoid cell lines (NA12878 and NA10855). We generated VCF files using variants identified in these data, and then evaluated the power and false positive rate of our approach to detect same species contamination. Our simulation experiments show that our method can detect levels of contamination as low as 5% with reasonable false positive rates. Results in real data have sensitivity above 99.99% and specificity at 90.24%, even in the presence of DNA degradation that has similar features to contaminated samples. Additionally, the approach can identify the difference between mixture of tumor-normal cells and contamination. We provide an R software implementation of our approach using the defcon()function in the vanquish: Variant Quality Investigation Helper R package on CRAN.
DPAC: a tool for Differential Poly(A) Site usage from poly(A)–targeted RNAseq data
Authors: Routh Andrew 
Published: January 2019

AbstractPoly(A)-tail targeted RNAseq approaches, such as 3’READS, PAS-seq and Poly(A)-ClickSeq, are becoming popular alternatives to random-primed RNAseq for simplified gene expression analyses as well as to measure changes in poly(A) site usage. We and others have recently demonstrated that these approaches perform similarly to other RNAseq strategies, while saving on the volume of sequencing data required and providing a simpler library synthesis strategy. Here, we present DPAC; a streamlined pipeline for the preprocessing of poly(A)-tail targeted RNAseq data, mapping of poly(A)-sites and poly(A) clustering, and determination of differential poly(A) site usage using DESeq2. Changes in poly(A) site usage is simultaneously used to report differential gene expression, differential terminal exon usage and alternative polyadenylation (APA).
Phylogenetic systematics and evolution of the spider infraorder Mygalomorphae using genomic scale data
Authors: Opatova Vera , Hamilton Chris A. , Hedin Marshal , de Oca Laura Montes , Král Jiří , Bond Jason E. 
Published: January 2019

AbstractThe Infraorder Mygalomorphae is one of the three main lineages of spiders comprising over 3,000 nominal species. This ancient group has a world-wide distribution that includes among its ranks large and charismatic taxa such as tarantulas, trapdoor spiders, and highly venomous funnel web spiders. Based on past molecular studies using Sanger-sequencing approaches, numerous mygalomorph families (e.g., Hexathelidae, Ctenizidae, Cyrtaucheniidae, Dipluridae and Nemesiidae) have been identified as non-monophyletic. However, these data were unable to sufficiently resolve the higher-level (intra- and interfamilial) relationships such that the necessary changes in classification could be made with confidence. Here we present the most comprehensive phylogenomic treatment of the spider infraorder Mygalomorphae conducted to date. We employ 472 loci obtained through Anchored Hybrid Enrichment to reconstruct relationships among all the mygalomorph spider families and estimate the timeframe of their diversification. We performed an extensive generic sampling of all currently recognized families, which has allowed us to assess their status, and as a result, propose a new classification scheme. Our generic-level sampling has also provided an evolutionary framework for revisiting questions regarding silk use in mygalomorph spiders. The first such analysis for the group within a strict phylogenetic framework shows that a sheet web is likely the plesiomorphic condition for mygalomorphs, as well as providing hints to the ancestral foraging behavior for all spiders. Our divergence time estimates, concomitant with detailed biogeographic analysis, suggest that both ancient continental-level vicariance and more recent dispersal events have played an important role in shaping modern day distributional patterns. Based on our results, we relimit the generic composition of the Ctenizidae, Cyrtaucheniidae, Dipluridae and Nemesiidae. We also elevate five subfamilies to family rank: Anamidae (NEW RANK), Euagridae (NEW RANK), Ischnothelidae (NEW RANK), Pycnothelidae (NEW RANK), and Bemmeridae (NEW RANK). The three families Hermachidae (NEW FAMILY), Microhexuridae (NEW FAMILY), and Stasimopidae (NEW FAMILY) are newly proposed. Such a major rearrangement in classification, recognizing eight newly established family-level rank taxa, is the largest the group has seen in over three decades since Raven’s (1985) taxonomic treatment.
Climate warming and plant biomechanical defences: Silicon addition contributes to herbivore suppression in a pasture grass
Authors: Johnson Scott N. , Ryalls James M. W. , Barton Craig V. M. , Tjoelker Mark G. , Wright Ian J. , Moore Ben D. 
Published: January 2019

Abstract

Plants, notably the Poaceae, often accumulate large amounts of silicon (Si) from the soil. Si has multiple functional roles, particularly for alleviating abiotic and biotic stresses (e.g., defence against herbivores). Recent evidence suggests that environmental change, including temperature changes, can diminish Si accumulation which could affect functions such as herbivore defence.

Using a field warming experiment, we grew a pasture grass (Phalaris aquatica) that was either supplemented or untreated with Si (+Si and −Si, respectively) under ambient and elevated (+2.8°C above ambient) air temperatures. We quantified soil water, plant growth rates, Si accumulation, leaf biomechanical properties and in situ relative growth rates of a herbivorous global insect pest (Helicoverpa armigera).

Si supplementation promoted shoot and root biomass by c. 48% and 61%, respectively under ambient temperatures, but these gains were not apparent under warmed conditions.

Warmer temperatures reduced Si uptake by −Si plants by c. 17%, potentially due to the lower levels of soil water content in warmed plots. Si supplementation, however, increased Si accumulation in leaves by c. 24% in warmed plots restoring Si levels to those seen under ambient temperatures.

Si supplementation enhanced biomechanical properties in the leaves, but this was only statistically significant under ambient temperatures; leaves of +Si plants required 42% more force to fracture and were 30% tougher at the midrib than leaves of −Si plants. The relative growth rates of H. armigera declined by 56% when feeding on +Si plants under ambient temperatures, and while Si supplementation caused a trend towards declining herbivore growth rates under warmer conditions, this was not statistically significant.

We conclude that climate warming may mitigate the beneficial effects of Si on Phalaris aquatica in the short term, potentially by reducing Si uptake. While Si uptake can be restored with Si supplementation, Si‐enhanced biomechanical defences against a global pest may not be fully restored under warmer temperatures.

A plain language summary is available for this article.
Outcomes from cytoreduction and hyperthermic intraperitoneal chemotherapy for appendiceal epithelial neoplasms
Authors: Narasimhan Vignesh , Pham Toan , Warrier Satish , Craig Lynch A. , Michael Michael , Tie Jeanne , Ramsay Robert , Heriot Alexander 
Published: January 2019

BackgroundAppendiceal epithelial neoplasms are rare cancers. Management of peritoneal disease from appendiceal neoplasms has historically been with debulking surgery. In recent decades, the advent of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard of care. Here, we report our single institution 10‐year experience with CRS and HIPEC for appendiceal neoplasms.MethodsThis is a retrospective review from 1 January 2008 to 1 June 2017 of all patients undergoing CRS and HIPEC for appendiceal neoplasms. Institutional ethics approval was granted for this project.ResultsOne hundred and seventy‐two patients underwent 208 CRSs during this time. Overall, 83.72% of patients had one CRS and HIPEC procedure. Pseudomyxoma peritonei from a perforated appendiceal mucinous neoplasm accounted for 67.9% of cases. The median peritoneal carcinomatosis index (PCI) was 14, with complete cytoreduction achieved in 74.2% of patients. Fifty‐four percent of patients had at least one complication, with one (0.5%) peri‐operative mortality in our cohort. For the entire cohort, the median overall survival was 104 months and a 5‐year survival of 75%. In those having a complete cytoreduction, 5‐year survival was 90%, with a median disease free interval of 63 months. PCI and completeness of cytoreduction were independent predictors of overall survival.ConclusionOur results demonstrate that CRS and HIPEC for appendiceal neoplasms are safe and effective. Despite carrying some morbidity, it offers patients an excellent disease free and overall survival.