bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scalable unified framework of total and allele-specific counts for cis-QTL, fine-mapping, and prediction
Authors: Liang Yanyu , Aguet François , Barbeira Alvaro , Ardlie Kristin , Im Hae Kyung 
Published: April 2020

AbstractGenome-wide association studies (GWAS) have been highly successful in identifying genomic loci associated with complex traits. However, identification of the causal genes that mediate these associations remains challenging, and many approaches integrating transcriptomic data with GWAS have been proposed. However, there currently exist no computationally scalable methods that integrate total and allele-specific gene expression to maximize power to detect genetic effects on gene expression. Here, we describe a unified framework that is scalable to studies with thousands of samples. Using simulations and data from GTEx, we demonstrate an average power gain equivalent to a 29% increase in sample size for genes with sufficient allele-specific read coverage. We provide a suite of freely available tools, mixQTL, mixFine, and mixPred, that apply this framework for mapping of quantitative trait loci, fine-mapping, and prediction.
Ontogeny and function of the circadian clock in intestinal organoids
Authors: Rosselot Andrew E. , Park Miri , Matsu-Ura Toru , Wu Gang , Flores Danilo E. , Subramanian Krithika R. , Lee Suengwon , Sundaram Nambirajan , Broda Taylor R. , McCauley Heather A. , Hawkins Jennifer A. , Chetal Kashish , Salomonis Nathan , Shroyer Noah F. , Helmrath Michael A. , Wells James M. , Hogenesch John B. , Moore Sean R. , Hong Christian I. 
Published: April 2020

AbstractCircadian rhythms regulate diverse aspects of gastrointestinal physiology ranging from the composition of microbiota to motility. However, development of the intestinal circadian clock and detailed molecular mechanisms regulating circadian physiology of the intestine remain largely unknown. The lack of appropriate human model systems that enable organ- and/or diseasespecific interrogation of clock functions is a major obstacle hindering advancements of translational applications using chronotherapy. In this report, we show that both pluripotent stem cell-derived human intestinal organoids engrafted into mice and patient-derived human intestinal enteroids (HIEs) possess robust circadian rhythms, and demonstrate circadian phase-dependent necrotic cell death responses toClostridium difficiletoxin B (TcdB). Intriguingly, mouse and human enteroids demonstrate anti-phasic necrotic cell death responses. RNA-Seq data show ~4% of genes are rhythmically expressed in HIEs. Remarkably, we observe anti-phasic gene expression ofRac1, a small GTPase directly inactivated by TcdB, between mouse and human enteroids. Importantly, the observed circadian time-dependent necrotic cell death response is abolished in both mouse enteroids and human intestinal organoids (HIOs) lacking robust circadian rhythms. Our findings uncover robust functions of circadian rhythms regulating critical clock-controlled genes (CCGs) in human enteroids governing organism-specific, circadian phasedependent necrotic cell death responses. Our data highlight unique differences between mouse and human enteroids, and lay a foundation for human organ- and disease-specific investigation of clock functions using human organoids for translational applications.
DNA micro-disk for the management of DNA-based data storage with index and write-once-read-many (WORM) memory features
Authors: Choi Yeongjae , Bae Hyung Jong , Lee Amos C. , Choi Hansol , Lee Daewon , Ryu Taehoon , Hyun Jinwoo , Kim Seojoo , Kim Hyeli , Song Suk-Heung , Kim Kibeom , Park Wook , Kwon Sunghoon 
Published: April 2020

AbstractDNA-based data storage has attracted attention because of its higher physical density of the data and longer retention time than those of conventional digital data storage1–7. However, previous DNA-based data storage lacked index features and the data quality of storage after a single access is not preserved, obstructing its industrial use. Here, we propose DNA micro-disks, quick response (QR)-coded micro-sized disks that harbour data-encoded DNA molecules for the efficient management of DNA-based data storage. We demonstrate the two major features that previous DNA-based data storage studies could not achieve. One feature is accessing data items efficiently by indexing the data-encoded DNA library. Another is achieving write-once-read-many (WORM) memory through the immobilization of DNA molecules on the disk and their enrichment throughin situDNA production. Through these features, the reliability of DNA-based data storage was increased by allowing multiple accession of data-encoded DNA without data loss.
Rapid computations of spectrotemporal prediction error support perception of degraded speech
Authors: Sohoglu Ediz , Davis Matthew H. 
Published: April 2020

AbstractHuman speech perception can be described as Bayesian perceptual inference but how are these Bayesian computations instantiated neurally? We use magnetoencephalographic recordings of brain responses to degraded spoken words as a function of signal quality and prior knowledge to demonstrate that spectrotemporal modulations in speech are more clearly represented in neural responses than alternative speech representations (e.g. spectrogram or articulatory features). We found an interaction between speech signal quality and expectations from prior written text on the quality of neural representations; increased signal quality enhanced neural representations of speech that mismatched with prior expectations, but led to greater suppression of speech that matched prior expectations. This interaction is a unique neural signature of prediction error computations and already apparent in neural responses within 250 ms of speech input. Our findings contribute towards the detailed specification of a computational model of speech perception based on predictive coding frameworks.
Duplication accelerates the evolution of structural complexity in protein quaternary structure
Authors: Leonard Alexander S. , Ahnert Sebastian E. 
Published: April 2020

AbstractGene duplication, from single genes to whole genomes, has been observed in organisms across all taxa. Despite its prevalence, the evolutionary benefits of this mechanism are the subject of ongoing debate. Gene duplication can significantly alter the self-assembly of protein quaternary structures, impacting the dosage or interaction proclivity. Here we use a lattice model of self-assembly as a coarse-grained representation of protein complex assembly, and show that it can be used to examine potential evolutionary advantages of duplication. Duplication provides a unique mechanism for increasing the evolvability of protein complexes by enabling the transformation of symmetric homomeric interactions into heteromeric ones. This transformation is extensively observed inin silicoevolutionary simulations of the lattice model, with duplication events significantly accelerating the rate at which structural complexity increases. These coarse-grained simulation results are corroborated with a large-scale analysis of complexes from the Protein Data Bank.
Investigating an in-silico approach for prioritizing antidepressant drug prescription based on drug-induced expression profiles and predicted gene expression
Authors: Shoaib Muhammad , Giacopuzzi Edorado , Pain Oliver , Fabbri Chiara , Magri Chiara , Minelli Alessandra , Lewis Cathryn M. , Gennarelli Massimo 
Published: April 2020

AbstractIn clinical practice, antidepressant prescription is a trial and error approach, which is time consuming and discomforting for patients. This study investigated an in-silico approach for ranking antidepressants based on their hypothetical likelihood of efficacy.We determined the transcriptomic profile of citalopram remitters by performing a transcriptomic-wide association study on STAR*D data (N =1163). The transcriptional profile of remitters was compared with 21 antidepressant-induced gene expression profiles in five human cell lines available in the connectivity map database. Spearman correlation, Pearson correlation, and the Kolmogorov Smirnov test were used to determine the similarity between antidepressant-induced profiles and remitter profiles, subsequently calculating the average rank of antidepressants across the three methods and a p-value for each rank by using a permutation procedure. The drugs with the top ranks were those having high positive correlation with the expression profiles of remitters and they may have higher chances of efficacy in the tested patients.In MCF7 (breast cancer cell line), escitalopram had the highest average rank, with an average rank higher than expected by chance (p=0.0014). In A375 (human melanoma) and PC3 (prostate cancer) cell lines, escitalopram and citalopram emerged as the second highest ranked antidepressants, respectively (p=0.0310 and 0.0276, respectively). In HA1E (kidney) and HT29 (colon cancer) cell types, citalopram and escitalopram did not fall among top antidepressants.The correlation between citalopram remitters’ and (es)citalopram-induced expression profiles in three cell lines suggests that our approach may be useful and with future improvements it can be applicable at the individual level to tailor treatment prescription.
Intrinsic, dynamic and effective connectivity among large-scale brain networks modulated by oxytocin
Authors: Jiang Xi , Ma Xiaole , Geng Yayuan , Zhao Zhiying , Zhou Feng , Zhao Weihua , Yao Shuxia , Yang Shimin , Zhao Zhongbo , Becker Benjamin , Kendrick Keith M. 
Published: April 2020

AbstractThe neuropeptide oxytocin is a key modulator of social-emotional behavior and its intranasal administration can influence the functional connectivity of brain networks involved in the control of attention, emotion and reward reported in humans. However, no studies have systematically investigated the effects oxytocin on dynamic or directional aspects of functional connectivity. The present study employed a novel computational framework to investigate these latter aspects in 15 oxytocin-sensitive regions using data from randomized placebo-controlled between-subject resting state functional MRI studies incorporating 200 healthy subjects. Results showed that oxytocin extensively modulated effective connectivity both between and within emotion, reward, salience and social cognition processing networks and their interactions with the default mode network, but had no effect on the frequency of dynamic changes. Top-down control over emotional processing regions such as the amygdala was particularly affected. Oxytocin effects were also sex-dependent, being more extensive in males. Overall, these findings suggest that modulatory effects of oxytocin on both within- and between-network interactions may underlie its functional influence on social-emotional behaviors, although in a sex-dependent manner. Furthermore, they demonstrate a useful approach to determining pharmacological influences on resting state effective connectivity and support oxytocin’s potential therapeutic use in psychiatric disorders.
Sex dependent gene activity in the human body
Authors: Hartman Robin J.G. , Mokry Michal , Pasterkamp Gerard , den Ruijter Hester M. 
Published: April 2020

AbstractMany pathophysiological mechanisms in human health and disease are dependent on sex. Systems biology approaches are successfully used to decipher human disease etiology, yet the effect of sex on gene network biology is mostly unknown. To address this, we used RNA-sequencing data of over 700 individuals spanning 24 tissues from the Genotype-Tissue Expression project to generate a whole-body gene activity map and quantified the sex differences per tissue. We found that of the 13,787 genes analyzed in 24 tissues, 20.1% of the gene activity is influenced by sex. For example, skeletal muscle was predominantly enriched with genes more active in males, whereas thyroid primarily contained genes more active in females. This was accompanied by consistent sex differences in pathway activity, including hypoxia, epithelial-to-mesenchymal transition, and inflammation over the human body. Furthermore, multi-organ analyses revealed consistent sex-dependent gene activity over numerous tissues which was accompanied by enrichment of transcription factor binding motifs in the promoters of these genes. Finally, we show that many sex-biased genes are known druggable targets. This emphasizes sex as a biological variable and the need to incorporate sex in systems biology studies.
Extent of similarity between agricultural and natural land covers shapes how biodiversity responds to agricultural expansion at landscape scales
Authors: Wilson Scott , Alavi-Shoushtari Niloofar , Pouliot Darren , Mitchell Gregory W. 
Published: April 2020

AbstractThe impact of agriculture on biodiversity depends on the extent and types of agriculture and the degree to which agricultural land contrasts with the natural ecosystem. Most research on the latter comes from studies on the influence of different agricultural types within a single ecosystem with far less study on how the natural ecosystem context shapes the response of biodiversity to agricultural production. We used citizen science data from agricultural areas in Canada’s Eastern Hardwood-Boreal (forest ecosystem, n=108 landscapes) and Prairie Pothole (prairie ecosystem, n=99) regions to examine how ecosystem context shapes the response of avian species diversity, functional diversity and abundance to the amount of arable crop and pastoral agriculture at landscape scales. Avian surveys were conducted along 8km transects of Breeding Bird Survey routes with land cover assembled within a 20km2landscape around each transect. The amount of agriculture at which species diversity peaked differed between the forest (15%) and prairie (51%) ecosystems, indicating that fewer species tolerated the expansion of agriculture in the former. In both ecosystems, functional diversity initially increased with agriculture and peaked at higher amounts (forest: 42%, prairie: 77%) than species diversity suggesting that functional redundancy was lost first as agriculture increased. Species turnover with increasing agriculture was primarily among functional groups in forest where a shift from a low to a high agriculture landscape led to a decline in the percent of the community represented by Neotropical migrants, insectivores, upper foliage gleaners and bark foragers, and an increase in the percent of the community represented by short-distance migrants, granivores, omnivores and ground gleaners. There were few distinct shifts in the percent of the community represented by different functional groups in the prairie ecosystem. Total abundance was the least sensitive measure examined in both ecosystems and indicated that species losses with agriculture are likely followed by numerical compensation from agriculture tolerant species. Our results highlight the importance of ecosystem context for understanding how biodiversity is affected by agricultural production with declines in diversity occurring at lower agricultural extents in ecosystems with lower similarity between natural and agricultural land covers. These findings allow for more specific conservation recommendations including managing for species intolerant to agriculture in prairie ecosystems and limiting the expansion of high contrast agriculture and the loss of semi-natural habitat, such as hedge rows, in historically forested ecosystems.
Comparative proteomics analysis identifies L-FABP as a putative biomarker of graft injury during liver transplantation
Authors: Chen Maogen , Lin Xiaohong , Zhang Yixi , Zhao Qiang , Mei Peiming , Chen Yinghua , Guo Zhiyong , Wu Linwei , Ma Yi , Wang Dongping , Ju Weiqiang , He Xiaoshun 
Published: April 2020

AbstractBackgroundTo a large extent the success of liver transplantation depends on quality of allografts. The molecular basis of the susceptibility of different liver allografts to transplant injury remains undefined.MethodsTransplanted liver samples were collected and divided into three groups: the optimal graft (OG) group, early allograft dysfunction (EAD) group, and primary nonfunction (PNF) group. iTRAQ comparative quantitative proteomic analysis and multiple reaction monitoring (MRM) verification was performed.ResultsMore than 160 differentially expressed proteins were detected in the PNF group, compared to 54 and 36 proteins in the EAD and OG groups respectively. Liver-type fatty acid-binding protein (L-FABP) was found as differentially expressed in both cold preserved and reperfused liver. Serum L-FABP level in donors was higher in the PNF and EAD groups than in the OG group. A lower tissue expression of L-FABP was observed in the PNF groups than other groups after reperfusion, indicating incompetent liver donor quality. In mouse ischemia reperfusion injury (IRI) model, the serum levels and tissue expression of L-FABP corresponded to the ALT variation curve.ConclusionsSuboptimal donor livers are more sensitive to ischemia reperfusion injury. L-FABP might be an effective biomarker for evaluating donor quality in liver transplantation.
Cognitive Deficits and Altered Functional Brain Network Organization in Pediatric Brain Tumor Patients
Authors: Anandarajah Hari , Seitzman Benjamin A. , McMichael Alana , Dworetsky Ally , Coalson Rebecca S. , Jiang Catherine , Gu Hongjie , Barbour Dennis L. , Schlaggar Bradley L. , Limbrick David D. , Rubin Joshua B. , Shimony Joshua S. , Perkins Stephanie M. 
Published: April 2020

AbstractPediatric brain tumor survivors experience significant cognitive sequelae from their diagnosis and treatment. The exact mechanisms of cognitive injury are poorly understood, and validated predictors of long-term cognitive outcome are lacking. Large-scale, distributed brain systems provide a window into brain organization and function that may yield insight into these mechanisms and outcomes.Here, we evaluated functional network architecture, cognitive performance, and brain-behavior relationships in pediatric brain tumor patients. Patients ages 4-18 years old with diagnosis of a brain tumor underwent awake resting state fMRI during regularly scheduled clinical visits and were tested with the NIH Toolbox Cognition Battery. We observed that functional network organization was significantly altered in patients compared to age- and sex-matched healthy controls, with the integrity of the dorsal attention network particularly affected. Moreover, patients demonstrated significant impairments in multiple domains of cognitive performance, including attention. Finally, a significant amount of variance of age-adjusted total composite scores from the Toolbox was explained by changes in segregation between the dorsal attention and default mode networks.Our results suggest that changes in functional network organization may provide insight into long-term changes in cognitive function in pediatric brain tumor patients.
Limitation by a shared mutualist promotes coexistence of multiple competing partners
Authors: Hammarlund Sarah P. , Gedeon Tomáš , Carlson Ross P. , Harcombe William 
Published: April 2020

AbstractAlthough mutualisms are often studied as simple pairwise interactions, they typically involve complex networks of interacting species. How multiple mutualistic partners that provide the same service and compete for resources are maintained in mutualistic networks is an open question. We use a model bacterial community in which multiple ‘partner strains’ ofEscherichia colicompete for a carbon source and exchange resources with a ‘shared mutualist’ strain ofSalmonella enterica. In laboratory experiments, competingE. colistrains readily coexist in the presence ofS. enterica, despite differences in their competitive abilities. We use ecological modeling to demonstrate that a shared mutualist can create temporary resource niche differentiation by limiting growth rates, even if yield is set by a resource external to a mutualism. This mechanism can extend to maintain multiple competing partner species. Our results improve our understanding of complex mutualistic communities and aid efforts to design stable microbial communities.
Multi-centre, multi-vendor reproducibility of 7T QSM and R2* in the human brain: results from the UK7T study
Authors: Rua Catarina , Clarke William T , Driver Ian D , Mougin Olivier , Morgan Andrew T. , Clare Stuart , Francis Susan , Muir Keith , Wise Richard , Carpenter Adrian , Williams Guy , Rowe James B , Bowtell Richard , Rodgers Christopher T 
Published: April 2020

AbstractWe present the reliability of ultra-high field T2* MRI at 7T, as part of the UK7T Network’s “Travelling Heads” study. T2*-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R2* maps. These reflect iron and myelin concentrations, which are altered in many pathophysiological processes. The relaxation parameters of human brain tissue are such that R2* mapping and QSM show particularly strong gains in contrast-to-noise ratio at ultra-high field (7T) vs clinical field strengths (1.5 - 3T). We aimed to determine the inter-subject and inter-site reproducibility of QSM and R2* mapping at 7T, in readiness for future multi-site clinical studies.MethodsTen healthy volunteers were scanned with harmonised single- and multi-echo T2*-weighted gradient echo pulse sequences. Participants were scanned five times at each “home” site and once at each of four other sites. The five sites had 1x Philips, 2x Siemens Magnetom, and 2x Siemens Terra scanners. QSM and R2* maps were computed with the Multi-Scale Dipole Inversion (MSDI) algorithm (https://github.com/fil-physics/Publication-Code). Results were assessed in relevant subcortical and cortical regions of interest (ROIs) defined manually or by the MNI152 standard space.Results and DiscussionMean susceptibility (χ) and R2* values agreed broadly with literature values in all ROIs. The inter-site within-subject standard deviation was 0.001 – 0.005 ppm (χ) and 0.0005 – 0.001 ms-1(R2*). For χ this is 2.1-4.8 fold better than 3T reports, and 1.1-3.4 fold better for R2*. The median ICC from within- and cross-site R2* data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B0inhomogeneity such as the inferior frontal cortex. Across sites, R2* values were more consistent than QSM in subcortical structures due to differences in B0-shimming. On a between-subject level, our measured χ and R2* cross-site variance is comparable to within-site variance in the literature, suggesting that it is reasonable to pool data across sites using our harmonised protocol.ConclusionThe harmonized UK7T protocol and pipeline delivers on average a 3-fold improvement in the coefficient of reproducibility for QSM and R2* at 7T compared to previous reports of multi-site reproducibility at 3T. These protocols are ready for use in multi-site clinical studies at 7T.
Rapid, sensitive, full genome sequencing of Severe Acute Respiratory Syndrome Virus Coronavirus 2 (SARS-CoV-2)
Authors: Paden Clinton R , Tao Ying , Queen Krista , Zhang Jing , Li Yan , Uehara Anna , Tong Suxiang 
Published: April 2020

AbstractSARS-CoV-2 recently emerged, resulting a global pandemic. Rapid genomic information is critical to understanding transmission and pathogenesis. Here, we describe validated protocols for generating high-quality full-length genomes from primary samples. The first employs multiplex RT-PCR followed by MinION or MiSeq sequencing. The second uses singleplex, nested RT-PCR and Sanger sequencing.