bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mantis: A Fast, Small, and Exact Large-Scale Sequence-Search Index
Authors: Pandey Prashant , Almodaresi Fatemeh , Bender Michael A. , Ferdman Michael , Johnson Rob , Patro Rob 
Published: November 2017

AbstractMotivationSequence-level searches on large collections of RNA-seq experiments, such as the NIH Sequence Read Archive (SRA), would enable one to ask many questions about the expression or variation of a given transcript in a population. Bloom filter-based indexes and variants, such as the Sequence Bloom Tree, have been proposed in the past to solve this problem. However, these approaches suffer from fundamental limitations of the Bloom filter, resulting in slow build and query times, less-than-optimal space usage, and large numbers of false positives.ResultsThis paper introduces Mantis, a space-efficient data structure that can be used to index thousands of rawread experiments and facilitate large-scale sequence searches on those experiments. Mantis uses counting quotient filters instead of Bloom filters, enabling rapid index builds and queries, small indexes, andexactresults, i.e., no false positives or negatives. Furthermore, Mantis is also a colored de Bruijn graph representation, so it supports fast graph traversal and other topological analyses in addition to large-scale sequence-level searches.In our performance evaluation, index construction with Mantis is 4.4× faster and yields a 20% smaller index than the state-of-the-art split sequence Bloom tree (SSBT). For queries, Mantis is 6× –108× faster than SSBT and has no false positives or false negatives. For example, Mantis was able to search for all 200,400 known human transcripts in an index of 2652 human blood, breast, and brain RNA-seq experiments in one hour and 22 minutes; SBT took close to 4 days and AllSomeSBT took about eight hours.Mantis is written inC++11and is available athttps://github.com/splatlab/mantis.
Overlooked polyploidies in lycophytes generalize their roles during the evolution of vascular plants
Authors: Wang Jinpeng , Yu Jigao , Sun Pengchuan , Li Chao , Song Xiaoming , Lei Tianyu , Li Yuxian , Yuan Jiaqing , Sun Sangrong , Ding Hongling , Duan Xueqian , Shen Shaoqi , Shen Yanshuang , Li Jing , Meng Fanbo , Xie Yangqin , Wang Jianyu , Hou Yue , Zhang Jin , Zhang Xianchun , Wang Xiyin 
Published: November 2017

AbstractSeed plants and lycophytes constitute the extant vascular plants. As a model lycophyte, Selaginalla moellendroffii was deciphered its genome, previously proposed to have avoided polyploidies, as key events contributing to the origination and fast expansion of seed plants. Here, using a gold-standard streamline recently proposed to deconvolute complex genomes, we reanalyzed the S. moellendroffii genome. To our surprise, we found clear evidence of multiple paleo-polyploidies, with one being recent (~ 13-15 millions of years ago or Mya), another one occurring about ~125-142 Mya, during the evolution of lycophytes, and at least 2 or 3 events being more ancient. Besides, comparison of reconstructed ancestral genomes of lycophytes and angiosperms shows that lycophytes were likely much more affected by paleo-polyploidies than seed plants. The present analysis here provides clear and solid evidence that polyploidies have contributed the successful establishment of all vascular plants on earth.
Integrative construction of regulatory region networks in 127 human reference epigenomes by matrix factorization
Authors: Liu Dianbo , Davila-Velderrain Jose , Zhang Zhizhuo , Kellis Manolis 
Published: November 2017

AbstractDespite large experimental and computational efforts aiming to dissect the mechanisms underlying disease risk, mapping cis-regulatory elements to target genes remains a challenge. Here, we introduce a matrix factorization framework to integrate physical and functional interaction data of genomic segments. The framework was used to predict a regulatory network of chromatin interaction edges linking more than 20,000 promoters and 1.8 million enhancers across 127 human reference epigenomes, including edges that are present in any of the input datasets. Our network integrates functional evidence of correlated activity patterns from epigenomic data and physical evidence of chromatin interactions. An important contribution of this work is the representation of heterogeneous data with different qualities as networks. We show that the unbiased integration of independent data sources suggestive of regulatory interactions produces meaningful associations supported by existing functional and physical evidence, correlating with expected independent biological features.
Modified antibiotic adjuvant ratios can slow and steer the evolution of resistance: co-amoxiclav as a case study
Authors: Allen Richard C. , Brown Sam P. 
Published: November 2017

AbstractAs the spread of antibiotic resistance outstrips the introduction of new antibiotics, reusing existing antibiotics is increasingly important. One promising method is to combine antibiotics with synergistically acting adjuvants that inhibit resistance mechanisms, allowing drug killing. Here we use co-amoxiclav (a commonly used and clinically important drug combination of the β-lactam antibiotic amoxicillin and the β-lactamase inhibitor clavulanate) to ask whether treatment efficacy and resistance evolution can be decoupled via component dosing modifications.A simple mathematical model predicts that different ratios of these two drug components can produce distinct evolutionary responses despite similar initial levels of control. We test this hypothesis by selecting Escherichia coli with a plasmid encoded β-lactamase (ESBL CTX-M-14), against different proportions of amoxicillin and clavulanate. Consistent with our theory, we found that while resistance evolved under all conditions, the component ratio influenced both the rate and mechanism of resistance evolution. Specifically, we found that the current clinical practice of high amoxicillin to clavulanate ratios resulted in the most rapid failure due to the evolution of gene dosing responses. Increased plasmid copy number allowed E. coli to increase β-lactamase dosing and effectively titrate out the low quantities of clavulanate, restoring amoxicillin resistance. In contrast, we found high clavulanate ratios were more robust - plasmid copy number did not increase, although porin or efflux resistance mechanisms were found, as in all drug ratios. Our results indicate that by changing the ratio of adjuvant to antibiotic we can slow and steer the path of resistance evolution. We therefore suggest the use of increased clavulanate dosing regimens to slow the rate of resistance evolution.
Microbial community structure and microbial networks correspond to nutrient gradients within coastal wetlands of the Laurentian Great Lakes
Authors: Horton Dean J. , Theis Kevin R. , Uzarski Donald G. , Learman Deric R. 
Published: November 2017

AbstractMicrobial communities within the soil of Laurentian Great Lakes coastal wetlands drive biogeochemical cycles and provide several other ecosystems services. However, there exists a lack of understanding of how microbial communities respond to nutrient gradients and human activity in these systems. This research sought to address the lack of understanding through exploration of relationships between nutrient gradients, microbial community diversity, and microbial networks. Significant differences in microbial community structure were found among coastal wetlands within the western basin of Lake Erie and all other wetlands studied (three regions within Saginaw Bay and one region in the Beaver Archipelago). These diversity differences coincided with higher nutrient levels within the Lake Erie region. Site-to-site variability also existed within the majority of the regions studied, suggesting site-scale heterogeneity may impact microbial community structure. Several subnetworks of microbial communities and individual community members were related to chemical gradients among wetland regions, revealing several candidate indicator communities and taxa which may be useful for Great Lakes coastal wetland management. This research provides an initial characterization of microbial communities among Great Lakes coastal wetlands and demonstrates that microbial communities could be negatively impacted by anthropogenic activities.
Hospitalized premature infants are colonized by related bacterial strains with distinct proteomic profiles
Authors: Brown Christopher. T. , Xiong Weili , Olm Matthew R. , Thomas Brian C. , Baker Robyn , Firek Brian , Morowitz Michael J. , Hettich Robert L. , Banfield Jillian F. 
Published: November 2017

AbstractDuring the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first three months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of which developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrates that the contributions of individual organisms to microbiome development depend on microbial community context.ImportanceHumans are colonized by microbes at birth, a process that is important to health and development. However, much remains to be known about the fine-scale microbial dynamics that occur during the colonization period. We conducted a genome-resolved study of microbial community composition, replication rates, and proteomes during the first three months of life of both healthy and sick premature infants. Infants were found to be colonized by similar microbes, but each underwent a distinct colonization trajectory.Interestingly, related microbes colonizing different infants were found to have distinct proteomes, indicating that microbiome function is not only driven by which organisms are present, but also largely depends on microbial responses to the unique set of physiological conditions in the infant gut.
Circuit models of low dimensional shared variability in cortical networks
Authors: Huang Chengcheng , Ruff Douglas A. , Pyle Ryan , Rosenbaum Robert , Cohen Marlene R. , Doiron Brent 
Published: November 2017

AbstractTrial-to-trial variability is a reflection of the circuitry and cellular physiology that makeup a neuronal network. A pervasive yet puzzling feature of cortical circuits is that despite their complex wiring, population-wide shared spiking variability is low dimensional with all neurons fluctuating en masse. Previous model cortical networks are at loss to explain this global variability, and rather assume it is from external sources. We show that if the spatial and temporal scales of inhibitory coupling match known physiology, model spiking neurons internally generate low dimensional shared variability that captures the properties ofin vivopopulation recordings along the visual pathway. Shifting spatial attention into the receptive field of visual neurons has been shown to reduce low dimensional shared variability within a brain area, yet increase the variability shared between areas. A top-down modulation of inhibitory neurons in our network provides a parsimonious mechanism for this attentional modulation, providing support for our theory of cortical variability. Our work provides a critical and previously missing mechanistic link between observed cortical circuit structure and realistic population-wide shared neuronal variability and its modulation.
Don’t throw out the sympatric species with the crater lake water: fine-scale investigation of introgression provides weak support for functional role of secondary gene flow in one of the clearest examples of sympatric speciation
Authors: Richards Emilie J. , Poelstra Jelmer W. , Martin Christopher H. 
Published: November 2017

AbstractGenomic data has revealed complex histories of colonization and repeated gene flow previously unrecognized in some of the most celebrated examples of sympatric speciation and radiation. However, much of the evidence for secondary gene flow into these radiations comes from genome-wide tests, which tells us little about how gene flow potentially influenced sympatric diversification. Here we investigated whole genomes of Barombi Mbo crater lake cichlids for fine-scale patterns of introgression between species with neighboring riverine cichlid populations. We did find evidence of secondary gene flow into the radiation scattered across < 0.24% of the genome; however, the functional and genetic diversity in these regions paint no clear picture of how that variation could have contributed to the ecological and morphological diversity found in the lake. Our results suggest that either variation in novel genetic pathways introduced during secondary gene flow contributed to the radiation, or that secondary gene flow was predominantly neutral with respect to the diversification processes. We also found evidence for differential assortment of ancestral polymorphism found in riverine populations between sympatric sister species, suggesting the presence of a hybrid swarm in the past. While the history of gene flow and colonization appears to be more complicated than once thought, the lack of compelling evidence for secondary gene flow influencing diversification suggests that we should not yet rule out one of the most celebrated examples of sympatric speciation in nature.
Quadratic Programming Data Descriptors for Abnormal Beat Detection in ECG Recordings
Authors: Minhas Fayyaz ul Amir Afsar 
Published: November 2017

AbstractThis paper analyzes the efficacy of applying one class classifiers (OCCs) to the problem of abnormal beat detection in ECG. It also proposes a novel OCC called Quadratic Programming Dissimilarity representation based Data Descriptor (QPDDD). A comparison of the proposed classification technique with existing classifiers over the MIT-BIH arrhythmia database is presented. Results show that OCCs coupled with wavelet domain features present a practical, robust and scalable solution for handling inter-individual variability in ECG patterns of different types of cardiac beats. An equal error rate of 90-95% was obtained for the MIT-BIH arrhythmia database depending upon the amount of training data used. A major advantage of the proposed scheme is that it requires only normal beats during its training. Another advantage is that it is able to handle inter-individual differences in ECG morphologies as the training takes place separately for each individual.
An agent-based model of cattle grazing toxic Geyer’s larkspur
Authors: Jablonski Kevin E. , Boone Randall B. , Meiman Paul J. 
Published: November 2017

AbstractBy killing cattle and otherwise complicating management, the many species of larkspur (Delphiniumspp.) present a serious, intractable, and complex challenge to livestock grazing management in the western United States. Among the many obstacles to improving our understanding of cattle-larkspur dynamics has been the difficulty of testing different grazing management strategies in the field, as the risk of dead animals is too great. Agent-based models (ABMs) provide an effective method of testing alternate management strategies without risk to livestock. ABMs are especially useful for modeling complex systems such as livestock grazing management, and allow for realistic bottom-up encoding of cattle behavior. Here, we introduce a spatially-explicit, behavior-based ABM of cattle grazing in a pasture with a dangerous amount of Geyer’s larkspur (D. geyeri). This model tests the role of herd cohesion and stocking density in larkspur intake, finds that both are key drivers of larkspur-induced toxicosis, and indicates that alteration of these factors within realistic bounds can mitigate risk. Crucially, the model points to herd cohesion, which has received little attention in the discipline, as playing an important role in lethal acute toxicosis. As the first ABM to model grazing behavior at realistic scales, this study also demonstrates the tremendous potential of ABMs to illuminate grazing management dynamics, including fundamental aspects of livestock behavior amidst ecological heterogeneity.
Electrophysiological signatures of spatial boundaries in the human subiculum
Authors: Lee Sang Ah , Miller Jonathan F. , Watrous Andrew J. , Sperling Michael , Sharan Ashwini , Worrell Gregory A. , Berry Brent M , Jobst Barbara C. , Davis Kathryn A. , Gross Robert E. , Lega Bradley , Sheth Sameer , Das Sandhitsu R. , Stein Joel M. , Gorniak Richard , Rizzuto Daniel S. , Jacobs Joshua 
Published: November 2017

AbstractEnvironmental boundaries play a crucial role in spatial navigation and memory across a wide range of distantly-related species. In rodents, boundary representations have been identified at the single-cell level in the subiculum and entorhinal cortex of the hippocampal formation. While studies of hippocampal function and spatial behavior suggest that similar representations might exist in humans, boundary-related neural activity has not been identified electrophysiologically in humans until now. Here we present direct intracranial recordings from the hippocampal formation of surgical epilepsy patients while they performed a virtual spatial navigation task. Our results suggest that encoding target locations near boundaries elicited stronger theta oscillations than for target locations near the center of the environment and that this difference cannot be explained by variables such as trial length, speed, or movement. These findings provide the first direct evidence of boundary-dependent neural activity localized in humans to the subiculum, the homologue of the hippocampal subregion in which most rodent boundary cells are found.Significance StatementSpatial computations using environmental boundaries are an integral part of the brain’s spatial mapping system. In rodents, border/boundary cells in the subiculum and entorhinal cortex reveal boundary coding at the single-neuron level. Although there is good reason to believe that such representations also exist in humans, the evidence has thus far been limited to fMRI studies that broadly implicate the hippocampus in boundary-based navigation. By combining intracranial recordings with high-resolution imaging of hippocampal subregions we identified, for the first time in humans, a neural marker of boundary representation in the subiculum.
The impact of tumor receptor heterogeneity on the response to anti-angiogenic cancer treatment
Authors: Li Ding , Finley Stacey D. 
Published: November 2017

AbstractMultiple promoters and inhibitors mediate angiogenesis, the formation of new blood vessels, and these factors represent potential targets for impeding vessel growth in tumors. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor targeted in anti-angiogenic cancer therapies. In addition, thrombospondin-1 (TSP1) is a major endogenous inhibitor of angiogenesis, and TSP1 mimetics are being developed as an alternative type of anti-angiogenic agent. The combination of bevacizumab, an anti-VEGF agent, and ABT-510, a TSP1 mimetic, has been tested in clinical trials to treat advanced solid tumors. However, the patients’ responses are highly variable and show disappointing outcomes. To obtain mechanistic insight into the effects of this combination anti-angiogenic therapy, we have constructed a novel whole-body systems biology model including the VEGF and TSP1 reaction networks. Using this molecular-detailed model, we investigated how the combination anti-angiogenic therapy changes the amounts of pro-angiogenic and anti-angiogenic complexes in cancer patients. We particularly focus on answering the question of how the effect of the combination therapy is influenced by tumor receptor expression, one aspect of patient-to-patient variability. Overall, this model complements the clinical administration of combination anti-angiogenic therapy, highlights the role of tumor receptor variability in the heterogeneous responses to anti-angiogenic therapy, and identifies the tumor receptor profiles that correlate with a high likelihood of a positive response to the combination therapy. Our model provides novel understanding of the VEGF-TSP1 balance in cancer patients at the systems-level and could be further used to optimize combination anti-angiogenic therapy.
Transposon insertional mutagenesis in Saccharomyces uvarum reveals trans-acting effects influencing species-dependent essential genes
Authors: Sanchez Monica R. , Payen Celia , Cheong Frances , Hovde Blake T. , Bissonnette Sarah , Arkin Adam P. , Skerker Jeffrey M. , Brem Rachel B. , Caudy Amy A. , Dunham Maitreya J. 
Published: November 2017

AbstractTo understand how complex genetic networks perform and regulate diverse cellular processes, the function of each individual component must be defined. Comprehensive phenotypic studies of mutant alleles have been successful in model organisms in determining what processes depend on the normal function of a gene. These results are often ported to newly sequenced genomes by using sequence homology. However, sequence similarity does not always mean identical function or phenotype, suggesting that new methods are required to functionally annotate newly sequenced species. We have implemented comparative analysis by high-throughput experimental testing of gene dispensability in Saccharomyces uvarum, a sister species of S. cerevisiae. We created haploid and heterozygous diploid Tn7 insertional mutagenesis libraries in S. uvarum to identify species dependent essential genes, with the goal of detecting genes with divergent functions and/or different genetic interactions. Comprehensive gene dispensability comparisons with S. cerevisiae predicted diverged dispensability at 12% of conserved orthologs, and validation experiments confirmed 22 differentially essential genes. Surprisingly, despite their differences in essentiality, these genes were capable of cross-species complementation, demonstrating that trans-acting factors that are background-dependent contribute to differential gene essentiality. This study demonstrates that direct experimental testing of gene disruption phenotypes across species can inform comparative genomic analyses and improve gene annotation. Our method can be widely applied in microorganisms to further our understanding of genome evolution.