Most tweeted biology preprints, last 24 hours
*There are gaps in historical Twitter data, most notably in spring 2020. This may result in some preprints appearing with less tweets than they should.
144 results found. For more information, click each entry to expand.
180 tweets bioRxiv bioinformatics
Motivation: A recurring challenge in interpreting single-cell RNA-seq data is the assessment of results in the context of existing genomic databases. Currently, there is no tool implementing automated, easy programmatic access to information stored in a diverse collection of large, public genomic databases. Results: gget is a free and open-source command-line tool and Python package that enables efficient querying of genomic databases. gget consists of a collection of separate but interoperable modules, each designed to facilitate one type of database querying required for single-cell RNA-seq data analysis in a single line of code. Availability: The manual and source code are available at https://github.com/pachterlab/gget.
171 tweets bioRxiv molecular biology
In vitro transcribed synthetic messenger RNAs (mRNAs) represent a novel therapeutic modality and are currently being evaluated for a wide range of clinical indications. To overcome the inherent immunogenicity of the synthetic mRNAs, as well as to increase the therapeutic efficacy of the molecules, RNA sequence optimization is routinely performed and modified uridine analogs - such as pseudouridine and N1-methyl-pseudouridine, are incorporated in the synthetic mRNA. To decipher the fidelity with which these modifications are incorporated during the in vitro transcription (IVT) process, here, we compared, the incorporation fidelity of uridine, pseudouridine, or N1-methyl-pseudouridine in multiple RNA sequences with different single-subunit DNA-dependent RNA polymerases (ssRNAPs). By comparing the incorporation of each modified base to that of the unmodified equivalent, we demonstrate that N1-methyl-pseudouridine is incorporated with higher fidelity than pseudouridine. Furthermore, the various ssRNAPs exhibit different error rates; however, the spectrum of mutations observed between the RNAPs is similar. We also show that the array of nucleotide misincorporation is not dependent on the template DNA sequence context and that the distribution of these misincorporated nucleotides is not localized to any specific region along the length of the RNA. Based on our findings, we introduce a novel protocol to improve uridine analog incorporation - without affecting total RNA yield - during IVT. Our proof-of-concept experiments and protocol for higher-fidelity incorporation of uridine analogs during IVT provide guidelines when choosing ssRNAPs for the generation of modified uridine-containing mRNAs in vitro.
28 tweets medRxiv epidemiology
Karina-Doris Vihta, Koen Pouwels, Tim EA Peto, Emma Pritchard, Thomas House, Ruth Studley, Emma Rourke, Duncan Cook, Ian Diamond, Derrick Crook, Philippa Matthews, Nicole Stoesser, David Eyre, Ann Sarah Walker, COVID-19 Infection Survey team
In a nationally representative UK community study, SARS-CoV-2 Omicron infections were associated with fewer lower, and more upper, respiratory tract symptoms. Increases in sore throat (also common in PCR-negative participants), and a marked reduction in loss of taste/smell (previously highly specific), make Omicron harder to detect with symptom-based testing algorithms.
25 tweets medRxiv epidemiology
Evidence from early observational studies suggested negative vaccine effectiveness for the SARS-CoV-2 Omicron variant. Using transmission modeling, we illustrated how increased contact between vaccinated individuals, vaccinated contact heterogeneity, paired with lower vaccine efficacies could produce negative measurements and how we can identify this mechanism via a key temporal signature.
22 tweets medRxiv epidemiology
Importance: There is limited evidence on the effectiveness of the BNT162b2 vaccine for children, particularly those 5-11 years and after the Omicron variant's emergence. Objective: To estimate BNT162b2 vaccine effectiveness against COVID cases and hospitalizations among children 5-11 years and 12-17 years during December, 2021 and January, 2022. Design: Analyses of cohorts constructed from linked statewide immunization, laboratory testing, and hospitalization databases. Setting/Participants: New York State children 5-17 years. Main outcomes/measures: New laboratory-confirmed COVID-19 cases and hospitalizations. Comparisons were made using the incidence rate ratio (IRR), comparing outcomes by vaccination status, and estimated vaccine effectiveness (VE: 1-[1/IRR]). Results: From December 13, 2021 to January 30, 2022, among 852,384 fully-vaccinated children 12-17 years and 365,502 children 5-11 years, VE against cases declined from 66% (95% CI: 64%, 67%) to 51% (95% CI: 48%, 54%) for those 12-17 years and from 68% (95% CI: 63%, 72%) to 12% (95% CI: 6%, 16%) for those 5-11 years. During the January 24-30 week, VE for children 11 years was 11% (95%CI -3%, 23%) and for those age 12 was 67% (95% CI: 62%, 71%). VE against hospitalization declined changed from 85% (95% CI: 63%, 95%) to 73% (95% CI: 53%, 87%) for children 12-17 years, and from 100% (95% CI: -189%, 100%) to 48% (95% CI: -12%, 75%) for those 5-11 years. Among children newly fully-vaccinated December 13, 2021 to January 2, 2022, VE against cases within two weeks of full vaccination for children 12-17 years was 76% (95% CI: 71%, 81%) and by 28-34 days it was 56% (95% CI: 43%, 63%). For children 5-11, VE against cases declined from 65% (95% CI: 62%, 68%) to 12% (95% CI: 8%, 16%) by 28-34 days. Conclusions and Relevance: In the Omicron era, the effectiveness against cases of BNT162b2 declined rapidly for children, particularly those 5-11 years. However, vaccination of children 5-11 years was protective against severe disease and is recommended. These results highlight the potential need to study alternative vaccine dosing for children and the continued importance layered protections, including mask wearing, to prevent infection and transmission.
19 tweets medRxiv epidemiology
Repeated emergence of SARS-CoV-2 variants with increased transmissibility necessitates rapid detection and characterization of new lineages. To address this need, we developed PyR0, a hierarchical Bayesian multinomial logistic regression model that infers relative transmissibility of all viral lineages across geographic regions, detects lineages increasing in prevalence, and identifies mutations relevant to transmissibility. Applying PyR0 to all publicly available SARS-CoV-2 genomes, we identify numerous substitutions that increase transmissibility, including previously identified spike mutations and many non-spike mutations within the nucleocapsid and nonstructural proteins. PyR0 forecasts growth of new lineages from their mutational profile, identifies viral lineages of concern as they emerge, and prioritizes mutations of biological and public health concern for functional characterization.
16 tweets medRxiv infectious diseases
Dean Follmann, Holly E. Janes, Olive D. Buhule, Honghong Zhou, Bethany Girard, Kristen Marks, Karen Kotloff, Michaël Desjardins, Lawrence Corey, Kathleen M. Neuzil, Jacqueline M Miller, Hana M. El Sahly, Lindsey R. Baden
Importance: The performance of immunoassays for determining past SARS-CoV-2 infection, which were developed in unvaccinated individuals, has not been assessed in vaccinated individuals. Objective: To evaluate anti-nucleocapsid antibody (anti-N Ab) seropositivity in mRNA-1273 vaccine efficacy trial participants after SARS-CoV-2 infection during the trial's blinded phase. Design: Nested analysis in a Phase 3 randomized, placebo-controlled vaccine efficacy trial. Nasopharyngeal swabs for SARS-CoV-2 PCR testing were taken from all participants on Day 1 and Day 29 (vaccination days), and during symptom-prompted illness visits. Serum samples from Days 1, 29, 57, and the Participant Decision Visit (PDV, when participants were informed of treatment assignment, median day 149) were tested for anti-N Abs. Setting: Multicenter, randomized, double-blind, placebo-controlled trial at 99 sites in the US. Participants: Trial participants were [≥] 18 years old with no known history of SARS-CoV-2 infection and at appreciable risk of SARS-CoV-2 infection and/or high risk of severe Covid-19. Nested sub-study consists of participants with SARS-CoV-2 infection during the blinded phase of the trial. Intervention: Two mRNA-1273 (Moderna) or Placebo injections, 28 days apart. Main Outcome and Measure: Detection of serum anti-N Abs by the Elecsys (Roche) immunoassay in samples taken at the PDV from participants with SARS-CoV-2 infection during the blinded phase. The hypothesis tested was that mRNA-1273 recipients have different anti-N Ab seroconversion and/or seroreversion profiles after SARS-CoV-2 infection, compared to placebo recipients. The hypothesis was formed during data collection; all main analyses were pre-specified before being conducted. Results: We analyzed data from 1,789 participants (1,298 placebo recipients and 491 vaccine recipients) with SARS-CoV-2 infection during the blinded phase (through March 2021). Among participants with PCR-confirmed Covid-19 illness, seroconversion to anti-N Abs at a median follow up of 53 days post diagnosis occurred in 21/52 (40%) of the mRNA-1273 vaccine recipients vs. 605/648 (93%) of the placebo recipients (p < 0.001). Higher SARS-CoV-2 viral copies at diagnosis was associated with a higher likelihood of anti-N Ab seropositivity (odds ratio 1.90 per 1-log increase; 95% confidence interval 1.59, 2.28). Conclusions and Relevance: As a marker of recent infection, anti-N Abs may have lower sensitivity in mRNA-1273-vaccinated persons who become infected. Vaccination status should be considered when interpreting seroprevalence and seropositivity data based solely on anti-N Ab testing Trial Registration: ClinicalTrials.gov NCT04470427
11 tweets medRxiv infectious diseases
Krishna Mohan Vadrevu, Siddharth Reddy, Harsh Jogdand, Brunda Ganneru, Nizam Mirza, VN Tripathy, Chandramani Singh, Vasant Khalatkar, Siddaiah Prasanth, Sanjay Rai, Raches Ella, William Blackwelder, Sai Prasad, Krishna Ella
Background: We assessed the safety, reactogenicity, and immunogenicity of BBV152 in an open-label age de-escalation study in three age cohorts of children from 18 years of age down to 2 years of age. Methods: This was a phase 2/3 open-label, multi-centre study done across six hospitals in India. All children received two 0.5mL doses of BBV152 (Covaxin(R), Bharat Biotech International Ltd., Hyderabad, India), which is the same formulation indicated in adults. Participants were monitored for adverse events, and post-vaccination blood draws were collected to assess neutralising antibodies. A total of 526 children were enrolled into Group 1 (ages 12 through 18 years, n=176), Group 2 (ages 6 through 12 years, n=175), Group 3 (ages 2 through 6 years, n=175). Findings: There were no serious adverse events, deaths, or withdrawals due to an adverse event during the study. Vaccination with BBV152 was generally well tolerated, with no substantial difference in reactogenicity profiles between the different age groups. Similar immune responses were measured as microneutralisation (MNT) antibody titers in all three age groups. Vaccine-induced MNT responses in all groups were comparable to BEI reference sera run in the same assay. Seroconversion (measured by Plaque Reduction Neutralization Test (PRNT)) achieved high levels (95-98%) in all three groups four weeks after the second vaccination. The PRNT GMT ratio was 1.76 (95%CI: 1.32-2.33) (GMT all children subgroup / GMT in adults) had a lower limit [≥] 1, indicating superior antibodies in children when compared to adults. Vaccine responses were skewed towards a Th1 response with IgG1/IgG4 ratios above 1. Interpretation: BBV152 is well tolerated and immunogenic in children from 18 years down to 2 years of age. Immunogenicity analysis (by PRNT) shows superior antibody responses were observed in children compared to adults, suggesting that BBV152 will also be efficacious in this age group.
9 tweets medRxiv infectious diseases
Hye Kyung Lee, Ludwig Knabl, Mary Walter, Yuhai Dai, Magdalena Fussl, Yasemin Caf, Claudia Jeller, Philipp Knabl, Martina Obermoser, Christof Baurecht, Norbert Kaiser, August Zabernigg, Gernot M. Wurdinger, Priscilla A. Furth, Lothar Hennighausen
Antibody response following Omicron infection is reported to be less robust than that to other variants. Here we investigated how prior vaccination and/or prior infection modulates that response. Disease severity, antibody responses and immune transcriptomes were characterized in four groups of Omicron-infected outpatients (n=83): unvaccinated/no prior infection, vaccinated/no prior infection, unvaccinated/prior infection and vaccinated/prior infection. The percentage of patients with asymptomatic or mild disease was highest in the vaccinated/no prior infection group (87%) and lowest in the unvaccinated/no prior infection group (47%). Significant anti-Omicron spike antibody levels and neutralizing activity were detected in the vaccinated group immediately after infection but were not present in the unvaccinated/no prior infection group. Within two weeks, antibody levels against Omicron, increased. Omicron neutralizing activity in the vaccinated group exceeded that of the prior infection group. No increase in neutralizing activity in the unvaccinated/no prior infection group was seen. The unvaccinated/prior infection group showed an intermediate response. We then investigated the early transcriptomic response following Omicron infection in these outpatient populations and compared it to that found in unvaccinated hospitalized patients with Alpha infection. Omicron infected patients showed a gradient of transcriptional response dependent upon prior vaccination and infection status that correlated with disease severity. Vaccinated patients showed a significantly blunted interferon response as compared to both unvaccinated Omicron infected outpatients and unvaccinated Alpha infected hospitalized patients typified by the response of specific gene classes such as OAS and IFIT that control anti-viral responses and IFI27, a predictor of disease outcome.
6 tweets bioRxiv microbiology
As of May 2022, Omicron BA.2 variant is the most dominant variant in the world. Thereafter, Omicron subvariants have emerged and some of them began outcompeting BA.2 in multiple countries. For instance, Omicron BA.2.11, BA.2.12.1 and BA.4/5 subvariants are becoming dominant in France, the USA and South Africa, respectively. In this study, we evaluated the sensitivity of these new Omicron subvariants (BA.2.11, BA.2.12.1 and BA.4/5) to eight therapeutic monoclonal antibodies (bamlanivimab, bebtelovimab, casirivimab, cilgavimab, etesevimab, imdevimab, sotrovimab and tixagevimab). Notably, we showed that although cilgavimab is antiviral against BA.2, BA.4/5 exhibits higher resistance to this antibody compared to BA.2. Since mutations are accumulated in the spike proteins of newly emerging SARS-CoV-2 variants, we suggest the importance of rapid evaluation of the efficiency of therapeutic monoclonal antibodies against novel SARS-CoV-2 variants.
6 tweets bioRxiv microbiology
SARS-CoV-2 variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that VOCs retain similar MHC-I downregulation capacity compared to the ancestral virus. However, VOCs exhibit a greater ability to suppress type I IFN than the ancestral virus. Although VOCs possess unique mutations within the ORF8 gene, which suppresses MHC-I expression, none of these mutations enhanced the ability of ORF8 to suppress MHC-I expression. Notably, MHC-I upregulation was strongly inhibited after the ancestral SARS-CoV-2 infection in vivo. Collectively, our data suggest that the ancestral SARS-CoV-2 already possesses an intrinsically potent MHC-I evasion capacity, and that further adaptation by the variants was not observed.
6 tweets bioRxiv immunology
Nathaniel Felbinger, David P. Trudil, Lawrence L. Loomis, Richard Ascione, Gregory R. Siragusa, Seiji Haba, Aidan Mucci, Mark Claycomb, Sebastian Snowberger, Brian Luke, Shirley Tsang, Stephen C. Francesconi
A multitude of studies have attempted to characterize the antibody response of individuals to the SARS-CoV-2 virus on a linear peptide level by utilizing peptide microarrays. These studies have helped to identify epitopes that have potential to be used for diagnostic tests to identify infected individuals, however the immunological responses of individuals who have received the currently available mRNA vaccines have not been characterized. We aimed to identify linear peptides of the SARS-CoV-2 spike protein that elicited high IgA or IgG binding activity and compare the immunoreactivity of infected individuals to those who received recommended doses of either the Moderna mRNA-1273 or Pfizer BNT162b2 vaccines by utilizing peptide microarrays. Our results revealed peptide epitopes of significant IgG binding among recently infected individuals, many of which are located near functional domains implicated in the high infectivity of SARS-CoV-2. Vaccinated individuals were found to have less intense antibody binding activity than those acutely infected, yet novel markers of IgG binding were identified in the vaccinated group.
5 tweets bioRxiv cell biology
Ultraviolet (UV) germicidal tools have recently gained attention as a disinfection strategy against the COVID-19 pandemic but the safety profile arising from their exposure have been controversial and impeded larger scale implementation. We compare the emerging 222-nm far UVC and 277-nm UVC LED disinfection modules with the traditional UVC mercury lamp emitting at 254 nm to understand their effects on human retinal cell line ARPE-19 and HEK-A keratinocytes. Cells illuminated with 222-nm far UVC survived while those treated with 254-nm and 277-nm wavelengths underwent apoptosis via JNK/ATF2 pathway. However, cells exposed to 222-nm far UVC presented the highest degree of DNA damage as evidenced by yH2AX staining. Globally, these cells presented transcriptional changes in cell cycle and senescence pathways. Thus, the introduction of 222-nm far UVC lamps for disinfection purposes should be carefully considered and designed with the inherent dangers involved.
5 tweets bioRxiv cell biology
The human SMC5/6 complex is a conserved guardian of genome stability and an emerging component of antiviral responses. These disparate functions likely require distinct mechanisms of SMC5/6 regulation. In yeast, Smc5/6 is regulated by its Nse5/6 subunits, but such regulatory subunits for human SMC5/6 are poorly defined. Here, we identify a novel SMC5/6 subunit called SIMC1 that contains SUMO interacting motifs (SIMs) and an Nse5-like domain. We isolated SIMC1 from the proteomic environment of SMC5/6 within polyomavirus large T antigen (LT)-induced subnuclear compartments. SIMC1 uses its SIMs and Nse5- like domain to localize SMC5/6 to polyomavirus replication centers (PyVRCs) at SUMO-rich PML nuclear bodies. SIMC1's Nse5-like domain binds to the putative Nse6 orthologue SLF2 to form an anti-parallel helical dimer resembling the yeast Nse5/6 structure. SIMC1-SLF2 structure-based mutagenesis defines a conserved surface region containing the N-terminus of SIMC1's helical domain that regulates SMC5/6 localization to PyVRCs. Furthermore, SLF1, which recruits SMC5/6 to DNA lesions, binds SLF2 analogously to SIMC1 and forms a distinct Nse5/6-like complex. Thus, two Nse5/6-like complexes independently regulate human SMC5/6: SIMC1-SLF2 responding to viral challenge and SLF1/2 recognizing DNA damage.
5 tweets medRxiv epidemiology
Yanshan Zhu, Conor J. Bloxham, Katina D. Hulme, Jane E Sinclair, Zhen Wei Marcus Tong, Lauren E. Steele, Ellesandra C. Noye, Jiahai Lu, Yao Xia, Keng Yih Chew, Janessa Pickering, Charles Gilks, Asha C. Bowen, Kirsty Short
The role of children in the spread of SARS-CoV-2 remains highly controversial. To address this issue, we performed a meta-analysis of the published literature on household SARS-CoV-2 transmission clusters (n=213 from 12 countries). Only 8 (3.8%) transmission clusters were identified as having a paediatric index case. Asymptomatic index cases were associated with a lower secondary attack in contacts than symptomatic index cases (estimate risk ratio [RR], 0.17; 95% confidence interval [CI], 0.09-0.29). To determine the susceptibility of children to household infections the secondary attack rate (SAR) in paediatric household contacts was assessed. The secondary attack rate in paediatric household contacts was lower than in adult household contacts (RR, 0.62; 95% CI, 0.42-0.91). These data have important implications for the ongoing management of the COVID-19 pandemic, including potential vaccine prioritization strategies.
5 tweets medRxiv epidemiology
Background: Long COVID is a post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection syndrome characterised by not recovering for several weeks or months following the acute episode. The effectiveness of COVID-19 vaccines against long-term symptoms of COVID-19 is not well understood. We determined whether vaccination was associated with the incidence of reporting long-term symptoms post-SARS-CoV-2 infection Methods: We invited individuals who were PCR tested for SARS-CoV-2 infection at participating hospitals between March 2020-November 2021 to fill an online questionnaire that included baseline demographics, details of their acute episode and information about symptoms they were currently experiencing. Using binomial regression, we compared vaccinated individuals with those unvaccinated and those uninfected in terms of self-reported symptoms post-acute infection. Results: We included 951 infected and 2437 uninfected individuals. Of the infected, 637(67%) were vaccinated. The most commonly reported symptoms were; fatigue (22%), headache (20%), weakness (13%), and persistent muscle pain (10%). After adjusting for follow-up time and baseline symptoms, those who received two doses less likely than unvaccinated individuals to report any of these symptoms by 64%, 54%, 57%, and 68% respectively, (Risk ratios 0.36, 0.46, 0.43, 0.32, p<0.04 in the listed sequence). Those who received two doses were no more likely to report any of these symptoms than individuals reporting no previous SARS-CoV-2 infection. Conclusions: Vaccination with at least two doses of COVID-19 vaccine was associated with a substantial decrease in reporting the most common post-acute COVID-19 symptoms, bringing it back to baseline. Our results suggest that, in addition to reducing the risk of acute illness, COVID-19 vaccination may have a protective effect against long COVID.
4 tweets bioRxiv scientific communication and education
Jerome Mariette, Odile Blanchard, Olivier Berne, Olivier Aumont, Julian Carrey, Anne-Laure Ligozat, Emmanuel Lellouch, Philippe E Roche, Gaek Guennebaud, Joel Thanwerdas, Philippe Bardou, Gerald Salin, Elise Maigne, Sophie Servan, Tamara Ben Ari
The scrutiny over the carbon footprint of academics has increased rapidly in the last few years. This has resulted in a series of publications providing various estimates of the carbon footprint of one or several research activities, principally at the scale of a university or a research center or, more recently, a field of research. The variety of tools or methodologies - on which these estimates rely - unfortunately prevents from any direct comparison because of the sensitivity of carbon footprint assessments to variations in the scope and to key parameters such as emission factors. In an effort to enabling a robust comparison of research carbon footprints across institutions, contexts or disciplines, we present an open-source web application, GES 1point5 designed to estimate the carbon footprint of a department, research lab or team in any country of the world with a transparent and common methodology. The current version of GES 1point5, open-source and freely available, takes into account the most common and often predominant emission sources in research labs: buildings, digital devices, commuting, and professional travel. GES 1point5 is developed by an interdisciplinary team of scientists from several public research institutions in France as part of the Labos 1point5 project. GES 1point5 is therefore presently tailored for the French context but can be adjusted to any national contexts by adjusting the values of emission factors. The versatility and usability of the software have been empirically validated by its adoption by several hundred research labs in France over the last 18 months. In addition to enabling the estimation and monitoring of greenhouse gas (GHG) emissions at the scale of a research lab, GES 1point5 is designed to aggregate the data entered by the labs and the corresponding GHG emissions estimates into a comprehensive database. GES 1point5 can therefore allow to (i) identify robust determinants of the carbon footprint of research activities across a network of research labs (ii) estimate the carbon footprint of research at the national scale. A preliminary analysis of the carbon footprint of more than one hundred laboratories is presented to illustrate the potential of the approach. While assessments of carbon footprints are often externalized onto extension services and proprietary softwares, GES 1point5 is designed as a hands-on, pedagogic and transparent tool for research labs to monitor and reduce their own carbon footprint. This internalization has strong positive co-benefits for academics in terms of awareness and empowerment. We further expect that international dissemination of GES 1point5 will contribute to establishing a global understanding of the drivers of the research carbon footprint worldwide and an identification of the levers to decrease it.
4 tweets bioRxiv bioinformatics
Long-read shotgun metagenomic sequencing is gaining in popularity and offers many advantages over short-read sequencing. The higher information content in long reads is useful for a variety of metagenomics analyses, including taxonomic profiling. The development of long-read specific tools for taxonomic profiling is accelerating, yet there is a lack of consensus regarding their relative performance. Here, we perform a critical benchmarking study using five long-read methods and four popular short-read methods. We applied these tools to several mock community datasets generated using Pacific Biosciences (PacBio) HiFi or Oxford Nanopore Technology (ONT) sequencing, and evaluated their performance based on read utilization, detection metrics, and relative abundance estimates. Our results show that long-read methods generally outperformed short-read methods. Short-read methods (including Kraken2, Bracken, Centrifuge, and MetaPhlAn3) produced many false positives (particularly at lower abundances), required heavy filtering to achieve acceptable precision (at the cost of reduced recall), and produced inaccurate abundance estimates. By contrast, several long-read methods displayed very high precision and acceptable recall without any filtering required, including BugSeq, MEGAN-LR using translation alignments (DIAMOND to NCBI nr) or nucleotide alignments (minimap2 to NCBI nt). Furthermore, in the PacBio HiFi datasets these long-read methods detected all species down to the 0.1% abundance level with high precision. Other long-read methods, such as MetaMaps and MMseqs2, required moderate filtering to reduce false positives to achieve a suitable balance between precision and recall. We found read quality affected performance for methods relying on protein prediction or exact kmer matching, and these methods performed better with PacBio HiFi datasets. We also found that long-read datasets with a large proportion of shorter reads (<2kb length) resulted in lower precision and worse abundance estimates, relative to length-filtered datasets. Finally, for a given mock community we found that the long-read datasets produced significantly better results than short-read datasets, demonstrating clear advantages for long-read metagenomic sequencing. Our critical assessment of available methods provides recommendations for current research using long reads and establishes a baseline for future benchmarking studies.
4 tweets medRxiv infectious diseases
Background: Reports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear. Methods: We conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naive individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel. Results: SARS-CoV-2-naive vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naive vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naive vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected. Conclusions: This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.
4 tweets bioRxiv bioinformatics
Spatial transcriptomics (ST) is a new technology that measures mRNA expression across thousands of spots on a tissue slice, while preserving information about the spatial location of spots. ST is typically applied to several replicates from adjacent slices of a tissue. However, existing methods to analyze ST data do not take full advantage of the similarity in both gene expression and spatial organization across these replicates. We introduce a new method PASTE (Probabilistic Alignment of ST Experiments) to align and integrate ST data across adjacent tissue slices leveraging both transcriptional similarity and spatial distances between spots. First, we formalize and solve the problem of pairwise alignment of ST data from adjacent tissue slices, or layers, using Fused Gromov-Wasserstein Optimal Transport (FGW-OT), which accounts for variability in the composition and spatial location of the spots on each layer. From these pairwise alignments, we construct a 3D representation of the tissue. Next, we introduce the problem of simultaneous alignment and integration of multiple ST layers into a single layer with a low rank gene expression matrix. We derive an algorithm to solve the problem by alternating between solving FGW-OT instances and solving a Non-negative Matrix Factorization (NMF) of a weighted expression matrix. We show on both simulated and real ST datasets that PASTE accurately aligns spots across adjacent layers and accurately estimates a consensus expression matrix from multiple ST layers. PASTE outperforms integration methods that rely solely on either transcriptional similarity or spatial similarity, demonstrating the advantages of combining both types of information.
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- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
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