bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implications of Genetic Distance to Reference andDe NovoGenome Assembly for Clinical Genomics in Africans
Authors: Shriner Daniel , Adeyemo Adebowale , Rotimi Charles N. 
Published: September 2020

AbstractIn clinical genomics, variant calling from short-read sequencing data typically relies on a pan-genomic, universal human reference sequence. A major limitation of this approach is that the number of reads that incorrectly map or fail to map increase as the reads diverge from the reference sequence. In the context of genome sequencing of genetically diverse Africans, we investigate the advantages and disadvantages of using ade novoassembly of the read data as the reference sequence in single sample calling. Conditional on sufficient read depth, the alignment-based and assembly-based approaches yielded comparable sensitivity and false discovery rates for single nucleotide variants when benchmarked against a gold standard call set. The alignment-based approach yielded coverage of an additional 270.8 Mb over which sensitivity was lower and the false discovery rate was higher. Although both approaches detected and missed clinically relevant variants, the assembly-based approach identified more such variants than the alignment-based approach. Of particular relevance to individuals of African descent, the assembly-based approach identified four heterozygous genotypes containing the sickle allele whereas the alignment-based approach identified no occurrences of the sickle allele. Variant annotation using dbSNP and gnomAD identified systematic biases in these databases due to underrepresentation of Africans. Using the counts of homozygous alternate genotypes from the alignment-based approach as a measure of genetic distance to the reference sequence GRCh38.p12, we found that the numbers of misassemblies, total variant sites, potentially novel single nucleotide variants (SNVs), and certain variant classes (e.g., splice acceptor variants, stop loss variants, missense variants, synonymous variants, and variants absent from gnomAD) were significantly correlated with genetic distance. In contrast, genomic coverage and other variant classes (e.g., ClinVar pathogenic or likely pathogenic variants, start loss variants, stop gain variants, splice donor variants, incomplete terminal codons, variants with CADD score ≥20) were not correlated with genetic distance. With improvement in coverage, the assembly-based approach can offer a viable alternative to the alignment-based approach, with the advantage that it can obviate the need to generate diverse human reference sequences or collections of alternate scaffolds.
INFERRED RESOLUTION THROUGH HERD IMMMUNITY OF FIRST COVID-19 WAVE IN MANAUS, BRAZILIAN AMAZON
Authors: Prowse Thomas A. A. , Purcell Tara , Baía-da-Silva Djane Clarys , Sampaio Vanderson , Monteiro Wuelton Marcelo , Wood James , Mueller Ivo , McVernon Jodie , Lacerda Marcus V. G. , Ross Joshua V. 
Published: September 2020

INTRODUCTORY PARAGRAPHAs in many other settings, peak excess mortality preceded the officially reported ‘first wave’ peak of the COVID-19 epidemic in Manaus, Brazil, reflecting delayed case recognition and limited initial access to diagnostic testing. To avoid early information bias, we used detailed age and gender stratified death certificate and hospitalisation data to evaluate the epidemic’s trajectory and infer the cause of its decline using a stochastic model. Our results are consistent with heterogenous transmission reducing over time due to the development of herd immunity. Relative to a baseline model that assumed homogenous mixing across Manaus, a model that permitted a small, self-isolated population fraction raised the estimated herd-immunity threshold from 28% to 30% and reduced the final attack rate from 86% to 65%. In the latter scenario, a substantial proportion of vulnerable, older individuals remained susceptible to infection. Given uncertainties regarding the distancing behaviours of population subgroups with different social and economic characteristics, and the duration of sterilising or transmission-modifying immunity in exposed individuals, we conclude that the potential for epidemic outbreaks remains, but that future waves of infection are likely to be much less pronounced than that already experienced.
Sex-specific lesion topographies explain outcomes after acute ischemic stroke
Authors: Bonkhoff Anna K. , Schirmer Markus D. , Bretzner Martin , Hong Sungmin , Regenhardt Robert W. , Brudfors Mikael , Donahue Kathleen L. , Nardin Marco J. , Dalca Adrian V. , Giese Anne-Katrin , Etherton Mark R. , Hancock Brandon L. , Mocking Steven J. T. , McIntosh Elissa C. , Attia John , Benavente Oscar R. , Bevan Stephen , Cole John W. , Donatti Amanda , Griessenauer Christoph J. , Heitsch Laura , Holmegaard Lukas , Jood Katarina , Jimenez-Conde Jordi , Kittner Steven J. , Lemmens Robin , Levi Christopher R. , McDonough Caitrin W. , Meschia James F. , Phuah Chia-Ling , Rolfs Arndt , Ropele Stefan , Rosand Jonathan , Roquer Jaume , Rundek Tatjana , Sacco Ralph L. , Schmidt Reinhold , Sharma Pankaj , Slowik Agnieszka , Söderholm Martin , Sousa Alessandro , Stanne Tara M. , Strbian Daniel , Tatlisumak Turgut , Thijs Vincent , Vagal Achala , Wasselius Johan , Woo Daniel , Zand Ramin , McArdle Patrick F. , Worrall Bradford B. , Jern Christina , Lindgren Arne , Maguire Jane , Bzdok Danilo , Wu Ona , Rost Natalia S. ,   on behalf of the MRI-GENIE and GISCOME Investigators and the International Stroke Genetics Consortium
Published: September 2020

AbstractAcute ischemic stroke affects men and women differently in many ways. In particular, women are oftentimes reported to experience a higher acute stroke severity than men. Here, we derived a low-dimensional representation of anatomical stroke lesions and designed a sex-aware Bayesian hierarchical modelling framework for a large-scale, well phenotyped stroke cohort. This framework was tailored to carefully estimate possible sex differences in lesion patterns explaining acute stroke severity (NIHSS) in 1,058 patients (39% female). Anatomical regions known to subserve motor and language functions emerged as relevant regions for both men and women. Female patients, however, presented a more widespread pattern of stroke severity-relevant lesions than male patients. Furthermore, particularly lesions in the posterior circulation of thelefthemisphere underlay a higher stroke severity exclusively in women. These sex-sensitive lesion pattern effects could be discovered and subsequently robustly replicated in two large independent, multisite lesion datasets. The constellation of findings has several important conceptual and clinical implications: 1) suggesting sex-specific functional cerebral asymmetries, and 2) motivating a sex-stratified approach to management of acute ischemic stroke. To go beyond sex-averaged stroke research, future studies should explicitly test whether acute therapies administered on the basis of sex-specific cutoff volumes of salvageable tissue will lead to improved outcomes in women after acute ischemic stroke.
Field competitiveness ofAedes albopictus[Diptera: Culicidae] irradiated males in pilot Sterile Insect Technique trials in Northern Italy
Authors: Bellini Romeo , Carrieri Marco , Balestrino Fabrizio , Puggioli Arianna , Malfacini Marco , Bouyer Jeremy 
Published: September 2020

AbstractVector-borne diseases account for 17% of infectious diseases, leading to more than one million deaths each year. Mosquitoes are responsible for 90% of the casualties and alternative control methods to insecticides are urgently needed, especially againstAedesvectors.Aedes albopictusis a particularly important species, causing major public health problems because it is a vector of several arboviruses and has a strong invasive behaviour. Various genetic control methods have been proposed to be integrated into the management strategies ofAedesspecies, among which the sterile insect technique (SIT), which proved efficient against various insect pests and vectors. However, the ability of released irradiated sterile male mosquitoes to compete with their wild counterparts and induce sterility in wild females, which is critical to the success of this strategy, remained poorly defined. Here, we assessed the field competitiveness ofAe. albopictusirradiated male using data from six release trials implemented in Northern Italy for three years. Sterile males were capable of inducing a good level of sterility in the wild female population, however with high variability in time and space. The field competitiveness of the released males was strongly negatively correlated with the ratio of sterile to wild males. This should be taken into consideration when designing future programmes to suppress field populations ofAedesmosquitoes.
Whole genome comparisons reveal panmixia among fall armyworm (Spodoptera frugiperda) from diverse locations
Authors: Schlum Katrina A. , Lamour Kurt , de Bortoli Caroline Placidi , Banerjee Rahul , Emrich Scott J. , Meagher Robert , Pereira Eliseu , Murua Maria Gabriela , Sword Gregory A. , Tessnow Ashley E. , Dillon Diego Viteri , Linares Ramirez Angela M. , Akutse Komivi S. , Schmidt-Jeffris Rebecca , Huang Fangneng , Reisig Dominic , Jurat-Fuentes Juan Luis 
Published: September 2020

AbstractThe fall armyworm (Spodoptera frugiperda(J.E. Smith)) is a highly polyphagous agricultural pest with long-distance migratory behavior threatening food security worldwide. This pest has a host range of >80 plant species, but two host strains are recognized based on their association with corn (C-strain) or rice and smaller grasses (R-strain). In this study, the population structure and genetic diversity in 55S. frugiperdasamples from Argentina, Brazil, Kenya, Puerto Rico and the United States (USA) were surveyed to further our understanding of whole genome nuclear diversity. Comparisons at the genomic level suggest panmixia in this population, other than a minor reduction in gene flow between the two overwintering populations in the continental USA that also corresponded to genetically distinct host strains. Two maternal lines were detected from analysis of mitochondrial genomes. We found members from the Eastern Hemisphere interspersed within both continental USA overwintering subpopulations, suggesting multiple individuals were likely introduced to Africa. Comparisons between laboratory-reared and field collectedS. frugiperdasupport similar genomic diversity, validating the experimental use of laboratory strains. Our research is the largest diverse collection of United StatesS. frugiperdawhole genome sequences characterized to date, covering eight continental states and a USA territory (Puerto Rico). The genomic resources presented provide foundational information to understand gene flow at the whole genome level amongS. frugiperdapopulations.
A versatile toolkit for CRISPR-Cas13-based RNA manipulation inDrosophila
Authors: Huynh Nhan , Depner Noah , Larson Raegan , King-Jones Kirst 
Published: September 2020

SummaryAdvances in CRISPR technology have immensely improved our ability to manipulate nucleic acids, and the recent discovery of the RNA-targeting endonuclease Cas13 adds even further functionality. Here, we show that Cas13 works efficiently inDrosophila, bothex vivoandin vivo. We tested 44 different Cas13 variants to identify enzymes with the best overall performance and showed that Cas13 could target endogenousDrosophilatranscriptsin vivowith high efficiency and specificity. We also developed Cas13 applications to edit mRNAs and target mitochondrial transcripts. Our vector collection represents a versatile tool collection to manipulate gene expression at the post-transcriptional level.
Droplet microfluidic sequencing of HIV genomes and integration sites
Authors: Sun Chen , Liu Leqian , Pérez Liliana , Li Xiangpeng , Liu Yifan , Xu Peng , Boritz Eli A. , Mullins James I. , Abate Adam R. 
Published: September 2020

AbstractSequencing individual HIV-proviruses and their adjacent cellular junctions can elucidate mechanisms of infected cell persistencein vivo. Here, we present a high throughput microfluidic method to sequence entire proviruses in their native integration site context. We used the method to analyze infected cells from people with HIV on suppressive antiretroviral therapy, demonstrating >90% capture and sequencing of paired proviral genomes and integration sites. This method should enable comprehensive genetic analysis of persistent HIV-infected cell reservoirs, providing important insights into the barriers to HIV cure.
Bleaching resistant corals retain heat tolerance following acclimatization to environmentally distinct reefs
Authors: Barott Katie L. , Huffmyer Ariana S. , Davidson Jennifer M. , Lenz Elizabeth A. , Matsuda Shayle B. , Hancock Joshua R. , Innis Teegan , Drury Crawford , Putnam Hollie M. , Gates Ruth D. 
Published: September 2020

AbstractUrgent action is needed to prevent the demise of coral reefs as the climate crisis leads to an increasingly warmer and more acidic ocean. Propagating climate change resistant corals to restore degraded reefs is one promising strategy; however, empirical evidence is needed to determine if resistance is retained following transplantation within or beyond a coral’s natal reef. Here we assessed the performance of bleaching-resistant individuals of two coral species following reciprocal transplantation between environmentally distinct reefs (lowvshigh diel variability) to determine if stress resistance is retained following transplantation. Critically, transplantation to either environment had no influence on coral bleaching resistance, indicating that this trait was relatively fixed and is thus a useful metric for selecting corals for reef restoration within their native range. In contrast, growth was highly plastic, and native performance was not predictive of performance in the novel environment. Coral metabolism was also plastic, with cross transplants of both species matching the performance of native corals at both reefs within three months. Coral physiology (autotrophy, heterotrophy, and metabolism) and overall fitness (survival, growth, and reproduction) were higher at the reef with higher flow and fluctuations in diel pH and dissolved oxygen, and did not differ between native corals and cross-transplants. Conversely, cross-transplants at the low-variability reef had higher fitness than native corals, thus increasing overall fitness of the recipient population. This experiment was conducted during a non-bleaching year, which suggests that introduction of these bleaching-resistant individuals will provide even greater fitness benefits to recipient populations during bleaching years. In summary, this study demonstrates that propagating and transplanting bleaching-resistant corals can elevate the resistance of coral populations to ocean warming while simultaneously maintaining reef function as the climate crisis worsens.
Chromosomal instability accelerates the evolution of resistance to anti-cancer therapies
Authors: Lukow Devon A. , Sausville Erin L. , Suri Pavit , Chunduri Narendra Kumar , Leu Justin , Kendall Jude , Wang Zihua , Storchova Zuzana , Sheltzer Jason M. 
Published: September 2020

AbstractAneuploidy is a ubiquitous feature of human tumors, but the acquisition of aneuploidy is typically detrimental to cellular fitness. To investigate how aneuploidy could contribute to tumor growth, we triggered periods of chromosomal instability (CIN) in human cells and then exposed them to a variety of different culture environments. While chromosomal instability was universally detrimental under normal growth conditions, we discovered that transient CIN reproducibly accelerated the ability of cells to adapt and thrive in the presence of anti-cancer therapeutic agents. Single-cell sequencing revealed that these drug-resistant populations recurrently developed specific whole-chromosome gains and losses. We independently derived one aneuploidy that was frequently recovered in cells exposed to paclitaxel, and we found that this chromosome loss event was sufficient to decrease paclitaxel sensitivity. Finally, we demonstrated that intrinsic levels of CIN correlate with poor responses to a variety of systemic therapies in a collection of patient-derived xenografts. In total, our results show that while chromosomal instability generally antagonizes cell fitness, it also provides phenotypic plasticity to cancer cells that can allow them to adapt to diverse stressful environments. Moreover, our findings suggest that aneuploidy may function as an under-explored cause of therapy failure in human tumors.
Whole Genome Variation of Transposable Element Insertions in a Maize Diversity Panel
Authors: Qiu Yinjie , O’Connor Christine H. , Coletta Rafael Della , Renk Jonathan S. , Monnahan Patrick J. , Noshay Jaclyn M. , Liang Zhikai , Gilbert Amanda , Anderson Sarah N. , McGaugh Suzanne E. , Springer Nathan M. , Hirsch Candice N. 
Published: September 2020

ABSTRACTIntact transposable elements (TEs) account for 65% of the maize genome and can impact gene function and regulation. Although TEs comprise the majority of the maize genome and affect important phenotypes, genome wide patterns of TE polymorphisms in maize have only been studied in a handful of maize genotypes, due to the challenging nature of assessing highly repetitive sequences. We implemented a method to use short read sequencing data from 509 diverse inbred lines to classify the presence/absence of 445,418 non-redundant TEs that were previously annotated in four genome assemblies including B73, Mo17, PH207, and W22. Different orders of TEs (i.e. LTRs, Helitrons, TIRs) had different frequency distributions within the population. LTRs with lower LTR similarity were generally more frequent in the population than LTRs with higher LTR similarity, though high frequency insertions with very high LTR similarity were observed. LTR similarity and frequency estimates of nested elements and the outer elements in which they insert revealed that most nesting events occurred very near the timing of the outer element insertion. TEs within genes were at higher frequency than those that were outside of genes and this is particularly true for those not inserted into introns. Many TE insertional polymorphisms observed in this population were tagged by SNP markers. However, there were also 19.9% of the TE polymorphisms that were not well tagged by SNPs (R2 < 0.5) that potentially represent information that has not been well captured in previous SNP based marker-trait association studies. This study provides a population scale genome-wide assessment of TE variation in maize, and provides valuable insight on variation in TEs in maize and factors that contribute to this variation.
Genetic analyses link the conserved inner membrane protein CvpA to the σEextracytoplasmic stress response
Authors: Warr Alyson R. , Giorgio Rachel T. , Waldor Matthew K. 
Published: September 2020

AbstractThe function ofcvpA, a bacterial gene predicted to encode an inner membrane protein, is largely unknown. Early studies inE. colilinkedcvpAto Colicin V secretion and recent work revealed that it is required for robust intestinal colonization by diverse enteric pathogens. In enterohemorrhagicE. coli(EHEC),cvpAis required for resistance to the bile salt deoxycholate (DOC). Here, we carried out genome-scale transposon-insertion mutagenesis and spontaneous suppressor analysis to uncovercvpA’sgenetic interactions and identify common pathways that rescue the sensitivity of a ΔcvpAEHEC mutant to DOC. Collectively, these screens led to the hypothesis that the ΔcvpAmutant is impaired in its capacity to activate the σE-mediated stress response. This idea was supported by showing that mutations that activate σE, either indirectly or through its direct overexpression, can restore the ΔcvpAmutant’s resistance to DOC. Analysis of the distribution of CvpA homologs revealed that this inner membrane protein is conserved across bacterial phyla, in both enteric and non-enteric bacteria that are not exposed to bile. Together, our findings suggest that CvpA may function in triggering activation of the σEstress response pathway in response to DOC as well as additional stimuli.ImportanceSeveral enteric pathogens, including Enterohemorrhagic E. coli (EHEC), requirecvpAto robustly colonize the intestine. This inner membrane is also important for secretion of a colicin and EHEC resistance to the bile salt deoxycholate, but its function is unknown. Genetic analyses carried out here suggest thatcvpAis required to trigger the σE stress response pathway in response to deoxycholate. Since CvpA is conserved across diverse bacterial phyla, we propose that this inner membrane protein is important for activation of this stress response pathway in response to diverse perturbations of the cell envelope.
Environmental drivers of plankton protist communities along latitudinal and vertical gradients in the oldest and deepest freshwater lake
Authors: David Gwendoline M. , Moreira David , Reboul Guillaume , Annenkova Nataliia V. , Galindo Luis J. , Bertolino Paola , López-Archilla Ana I. , Jardillier Ludwig , López-García Purificación 
Published: September 2020

SummaryIdentifying which abiotic and biotic factors determine microbial community assembly is crucial to understand ecological processes and predict how communities will respond to environmental change. While global surveys aim at addressing this question in the world’s oceans, equivalent studies in large freshwater systems are virtually lacking. Being the oldest, deepest and most voluminous freshwater lake on Earth, Lake Baikal offers a unique opportunity to test the effect of horizontal versus vertical gradients in community structure. Here, we characterized the structure of planktonic microbial eukaryotic communities (0.2-30 µm cell size) along a North-South latitudinal gradient (∼600 km) from samples collected in coastal and pelagic waters and from surface to the deepest zones (5-1400 m) using an 18S rRNA gene metabarcoding approach. Our results show complex and diverse protist communities dominated by alveolates (ciliates and dinoflagellates), ochrophytes and holomycotan lineages, with cryptophytes, haptophytes, katablepharids and telonemids in moderate abundance and many low-frequency lineages, including several typical marine members, such as diplonemids, syndinians and radiolarians. Depth had a strong significant effect on protist community stratification. By contrast, the effect of the latitudinal gradient was marginal and no significant difference was observed between coastal and surface open water communities. Co-occurrence network analyses showed that epipelagic communities are much more interconnected than meso- and bathypelagic communities and suggest specific biotic interactions between autotrophic, heterotrophic and parasitic lineages that influence protist community structure. Since climate change is rapidly affecting Siberia and Lake Baikal, our comprehensive protist survey constitutes a useful reference to monitor ongoing community shifts.Originality and Significance StatementLake Baikal is the oldest, deepest and most voluminous freshwater lake on Earth, offering a unique opportunity to test the effects of horizontal versus vertical gradients on microbial community structure. Using a metabarcoding approach, we studied planktonic microbial eukaryotes from Baikal water columns (5 up to 1,400 m depth) across a North-South latitudinal gradient (∼600 km), including coastal and pelagic areas. Our results show that depth has a strong effect on protist community assemblage, but not latitude (minor effect) or coastal vs. open water sites (no effect). Co-occurrence analyses also point to specific biotic interactions as drivers of community structure. This comprehensive survey constitutes a useful reference for monitoring active climate change effects in this ancient lake.