Featured
-
-
Article
| Open AccessMechanical forces drive a reorientation cascade leading to biofilm self-patterning
Bacterial biofilms exhibit complex spatiotemporal pattern formation. Here the authors report a collective cell reorientation cascade in growing Vibrio cholerae biofilms that leads to a differentially ordered, spatiotemporally coupled core-rim structure.
- Japinder Nijjer
- , Changhao Li
- & Jing Yan
-
Article
| Open AccessTowards inferring nanopore sequencing ionic currents from nucleotide chemical structures
Nanopore sequencing allows users to identify nucleotide sequence from ionic currents. Here, the authors use deep learning to facilitate the de novo identification of modified nucleotides, particularly methylated cytosine and guanine, from the measured ionic currents without the need for controls.
- Hongxu Ding
- , Ioannis Anastopoulos
- & Benedict Paten
-
Article
| Open AccessNetwork analysis reveals rare disease signatures across multiple levels of biological organization
Despite the clear causal relationship between genotype and phenotype in rare diseases, identifying the pathobiological mechanisms at various levels of biological organization remains a practical and conceptual challenge. Here, the authors introduce a network approach for evaluating the impact of rare gene defects across biological scales.
- Pisanu Buphamalai
- , Tomislav Kokotovic
- & Jörg Menche
-
Article
| Open AccessPotential global impacts of alternative dosing regimen and rollout options for the ChAdOx1 nCoV-19 vaccine
The ChAdOx1 nCoV-19 vaccine requires two doses, but under limited supply single dose regimens have also been considered. Here, the authors show using static transmission modelling that under certain conditions it is optimal to more expediently administer a single dose to a larger proportion of the population.
- Ricardo Aguas
- , Anouska Bharath
- & Rima Shretta
-
Article
| Open AccessThe generative capacity of probabilistic protein sequence models
Generative models have become increasingly popular in protein design, yet rigorous metrics that allow the comparison of these models are lacking. Here, the authors propose a set of such metrics and use them to compare three popular models.
- Francisco McGee
- , Sandro Hauri
- & Allan Haldane
-
Article
| Open AccessThe impact of the timely birth dose vaccine on the global elimination of hepatitis B
The timely hepatitis B birth dose vaccination is recommended for all new-borns by the WHO, but coverage is inconsistent. Here, the authors model the impact of scaling-up coverage in 110 low and middle income countries and assess how it may be affected by delays for example caused by the COVID-19 pandemic.
- Margaret J. de Villiers
- , Shevanthi Nayagam
- & Timothy B. Hallett
-
Article
| Open AccessDesigning the bioproduction of Martian rocket propellant via a biotechnology-enabled in situ resource utilization strategy
Returning from Mars to Earth requires propellant. The authors propose a biotechnology-enabled in situ resource utilization (bioISRU) process to produce a Mars specific rocket propellant, 2,3-butanediol, using cyanobacteria and engineered E. coli, with lower payload mass and energy usage compared to chemical ISRU strategies.
- Nicholas S. Kruyer
- , Matthew J. Realff
- & Pamela Peralta-Yahya
-
Article
| Open AccessBayesian log-normal deconvolution for enhanced in silico microdissection of bulk gene expression data
Deconvolution methods reveal individual cell types in complex tissues profiled by bulk methods. Here the authors present a Bayesian deconvolution method that outperforms existing methods when benchmarked on >700 datasets, especially in estimating cell-type-specific gene expression profiles.
- Bárbara Andrade Barbosa
- , Saskia D. van Asten
- & Yongsoo Kim
-
Article
| Open AccessGenome-wide detection of cytosine methylations in plant from Nanopore data using deep learning
Existing methods cannot profile genome-wide cytosine DNA methylations (5mCs) in all three contexts with acceptable accuracy. Here, the authors develop a deep learning tool to detect genome-wide 5mCs of all three contexts in plants with high accuracy from Nanopore reads.
- Peng Ni
- , Neng Huang
- & Jianxin Wang
-
Article
| Open AccessNationwide rollout reveals efficacy of epidemic control through digital contact tracing
The effectiveness of digital contact tracing for COVID-19 control remains uncertain. Here, the authors use data from the Smittestopp app, used in Norway in spring 2020, and estimate that 80% of nearby devices were detected by the app, and at least 11% of close contacts were not visible to manual contact tracing.
- Ahmed Elmokashfi
- , Joakim Sundnes
- & Olav Lysne
-
Article
| Open AccessEfficient and precise single-cell reference atlas mapping with Symphony
The number of single-cell RNA-seq datasets generated is increasing rapidly, making methods that map cell types to well-curated references increasingly important. Here, the authors propose an accurate method for mapping single cells onto a reference atlas in seconds.
- Joyce B. Kang
- , Aparna Nathan
- & Soumya Raychaudhuri
-
Article
| Open AccessGeographical drivers and climate-linked dynamics of Lassa fever in Nigeria
Lassa Fever is a rodent-borne viral haemorrhagic fever that is a public health problem in West Africa. Here, the authors develop a spatiotemporal model of the socioecological drivers of disease using surveillance data from Nigeria, and find evidence of climate sensitivity.
- David W. Redding
- , Rory Gibb
- & Chikwe Ihekweazu
-
Article
| Open AccessPossible future waves of SARS-CoV-2 infection generated by variants of concern with a range of characteristics
Understanding the potential impacts of new variants of SARS-CoV-2 is important for pandemic planning. Here, the authors develop a model incorporating hypothetical new variants with varying transmissibility and immune evasion properties, and use it to project possible future epidemic waves in the UK.
- Louise Dyson
- , Edward M. Hill
- & Matt J. Keeling
-
Article
| Open AccessDynamic memory to alleviate catastrophic forgetting in continual learning with medical imaging
In clinical practice, the continuous progress of image acquisition technology or diagnostic procedures and evolving imaging protocols hamper the utility of machine learning, as prediction accuracy on new data deteriorates. Here, the authors propose a continual learning approach to deal with such domain shifts occurring at unknown time points.
- Matthias Perkonigg
- , Johannes Hofmanninger
- & Georg Langs
-
Article
| Open AccessVEGA is an interpretable generative model for inferring biological network activity in single-cell transcriptomics
Developing interpretable models is a major challenge in single cell deep learning. Here we show that the VEGA variational autoencoder model, whose decoder wiring mirrors gene modules, can provide direct interpretability to the latent space further enabling the inference of biological module activity.
- Lucas Seninge
- , Ioannis Anastopoulos
- & Joshua Stuart
-
Article
| Open AccessMapping the glycosyltransferase fold landscape using interpretable deep learning
Glycosyltransferases (GT) are proteins that display extensive sequence and functional variation on a subset of 3D folds. Here, the authors use interpretable deep learning to predict 3D folds from sequence without the need for sequence alignment, which also enables the prediction of GTs with new folds.
- Rahil Taujale
- , Zhongliang Zhou
- & Natarajan Kannan
-
Article
| Open AccessModelling the persistence and control of Rift Valley fever virus in a spatially heterogeneous landscape
Rift Valley fever is a zoonotic haemorrhagic fever with complex transmission dynamics influenced by environmental variables and animal movements. Here, the authors develop a metapopulation model incorporating these factors and use it to identify the main drivers of transmission in the Comoros archipelago.
- Warren S. D. Tennant
- , Eric Cardinale
- & Raphaëlle Métras
-
Article
| Open AccessGeneralized and scalable trajectory inference in single-cell omics data with VIA
Scalable trajectory inference for multi-omic single cell datasets is challenging in terms of capturing non-tree complex topologies. Here the authors present a method, VIA, that scales to millions of cells across multiple omic modalities using lazy-teleporting random walks.
- Shobana V. Stassen
- , Gwinky G. K. Yip
- & Kevin K. Tsia
-
Article
| Open AccessQuantifying the unknown impact of segmentation uncertainty on image-based simulations
Image-based simulation for obtaining physical quantities is limited by the uncertainty in the underlying image segmentation. Here, the authors introduce a workflow for efficiently quantifying segmentation uncertainty and creating uncertainty distributions of the resulting physics quantities.
- Michael C. Krygier
- , Tyler LaBonte
- & Scott A. Roberts
-
Article
| Open AccessParental relatedness through time revealed by runs of homozygosity in ancient DNA
Little is known about how human parental relatedness varied across ancient populations. Runs of homozygosity (ROH) in the offspring’s genome can give clues. Here, the authors present a method to identify ROH in ancient genomes and infer low rates of close kin unions across most ancient populations.
- Harald Ringbauer
- , John Novembre
- & Matthias Steinrücken
-
Article
| Open AccessContact tracing is an imperfect tool for controlling COVID-19 transmission and relies on population adherence
Evaluations of the UK’s contact tracing programme have shown that it has had limited impact on COVID-19 control. Here, the authors show that with high levels of reporting and adherence, contact tracing could reduce transmission, but it should not be used as the sole control measure.
- Emma L. Davis
- , Tim C. D. Lucas
- & Petra Klepac
-
Article
| Open AccessTrade-offs between individual and ensemble forecasts of an emerging infectious disease
Newly emerged pathogens are inherently difficult to forecast, due to many unknowns about their biology early in an epidemic. Here, the authors assess forecasts of a suite of models during the Zika epidemic in Colombia, finding that the models that performed best changed over the course of the epidemic.
- Rachel J. Oidtman
- , Elisa Omodei
- & T. Alex Perkins
-
Article
| Open AccessBinding of regulatory proteins to nucleosomes is modulated by dynamic histone tails
The intrinsic disorder of histone tails poses challenges in their characterization. Here the authors apply extensive molecular dynamics simulations of the full nucleosome to show reversible binding to DNA with specific binding modes of different types of histone tails, where charge-altering modifications suppress tail-DNA interactions and may boost interactions between nucleosomes and nucleosome-binding proteins.
- Yunhui Peng
- , Shuxiang Li
- & Anna R. Panchenko
-
Article
| Open AccessA pre-registered short-term forecasting study of COVID-19 in Germany and Poland during the second wave
Forecasting models have been used extensively to inform decision making during the COVID-19 pandemic. In this preregistered and prospective study, the authors evaluated 14 short-term models for Germany and Poland, finding considerable heterogeneity in predictions and highlighting the benefits of combined forecasts.
- J. Bracher
- , D. Wolffram
- & Frost Tianjian Xu
-
Article
| Open AccessThe risk of indoor sports and culture events for the transmission of COVID-19
Mass gathering events represent a risk for transmission of SARS-CoV-2. Here, the authors describe an experimental indoor test event in which individual contacts were measured and use aerosol and epidemiological modelling to evaluate transmission risks of different types of restrictions in the arena.
- Stefan Moritz
- , Cornelia Gottschick
- & Rafael Mikolajczyk
-
Article
| Open AccessHigh COVID-19 transmission potential associated with re-opening universities can be mitigated with layered interventions
Reopening of universities to students following COVID-19 restrictions risks increased transmission due to high numbers of social contacts and the potential for asymptomatic transmission. Here, the authors use a mathematical model with social contact data to estimate the impacts of reopening a typical non-campus based university in the UK.
- Ellen Brooks-Pollock
- , Hannah Christensen
- & Leon Danon
-
Article
| Open AccessLineageOT is a unified framework for lineage tracing and trajectory inference
Lineage tracing and snapshots of transcriptional state at the single-cell level are powerful, complementary tools for studying development. Here, the authors propose a mathematical method combining lineage tracing with trajectory inference to improve our understanding of development.
- Aden Forrow
- & Geoffrey Schiebinger
-
Article
| Open AccessA genome-scale metabolic model of Saccharomyces cerevisiae that integrates expression constraints and reaction thermodynamics
Formulating metabolic networks mathematically can help researchers study metabolic diseases and optimize the production of industrially important molecules. Here, the authors propose a framework that allows to model eukaryotic metabolism considering gene expression and thermodynamic constraints.
- Omid Oftadeh
- , Pierre Salvy
- & Vassily Hatzimanikatis
-
Article
| Open AccessAn extended reconstruction of human gut microbiota metabolism of dietary compounds
The interplay between human diet and the gut microbiome is complex. Here, the authors present a model of human-microbiome interaction that can predict how phenolic compounds are metabolized by the human gut microbiome, identifying diet-specific metabolites in children of varied clinical conditions.
- Telmo Blasco
- , Sergio Pérez-Burillo
- & Francisco J. Planes
-
Article
| Open AccessNon-invasive hydrodynamic imaging in plant roots at cellular resolution
Existing methods for non-invasively monitoring water flow in plants have limited spatial/temporal resolution. Here, the authors report that Raman microspectroscopy, complemented by hydrodynamic modelling, can monitor hydrodynamics within living root tissues at cell- and sub-second-scale resolutions.
- Flavius C. Pascut
- , Valentin Couvreur
- & Kevin F. Webb
-
Article
| Open AccessDiffusion-mediated HEI10 coarsening can explain meiotic crossover positioning in Arabidopsis
Crossover numbers and positions are tightly controlled but the mechanism involved is still obscure. Here, the authors, using quantitative super-resolution cytogenetics and mathematical modelling, show that diffusion mediated coarsening of HEI10, an E3-ligase domain containing protein, may explain meiotic crossover positioning in Arabidopsis.
- Chris Morgan
- , John A. Fozard
- & Martin Howard
-
Article
| Open AccessImpact of tiered restrictions on human activities and the epidemiology of the second wave of COVID-19 in Italy
Italy introduced a system of tiered SARS-CoV-2 control measures in November 2020. Here, the authors quantify the effect of these measures on SARS-CoV-2 transmissibility and hospitalisation, and find reductions across all tiers with the greatest impacts associated with the most restrictive level.
- Mattia Manica
- , Giorgio Guzzetta
- & Stefano Merler
-
Article
| Open AccessDevelopment of a quantitative prediction algorithm for target organ-specific similarity of human pluripotent stem cell-derived organoids and cells
Quantitative methods to assess the quality of hPSC-derived organoids have not been developed. Here they present a prediction algorithm to assess the transcriptomic similarity between hPSC-derived organoids and the corresponding human target organs and perform validation on lung bud organoids, antral gastric organoids, and cardiomyocytes.
- Mi-Ok Lee
- , Su-gi Lee
- & Hyun-Soo Cho
-
Article
| Open AccessQuantitative imaging of transcription in living Drosophila embryos reveals the impact of core promoter motifs on promoter state dynamics
Here the authors decode how core promoter elements regulate rate limiting steps of transcription using quantitative live imaging, genetics and modeling in early Drosophila embryos. TATA-driven promoters require one rate-limiting step while INR promoters need an extra step associated with Pol II pausing.
- Virginia L. Pimmett
- , Matthieu Dejean
- & Mounia Lagha
-
Article
| Open AccessA machine learning approach to brain epigenetic analysis reveals kinases associated with Alzheimer’s disease
Array-based epigenome-wide association studies only test about 2% of the CpG sites in the genome. Here, the authors describe EWASplus, a supervised machine learning strategy that extends EWAS coverage to the entire genome, and use it to identify novel brain CpGs associated with Alzheimer’s disease.
- Yanting Huang
- , Xiaobo Sun
- & Zhaohui S. Qin
-
Article
| Open AccessAn on-demand, drop-on-drop method for studying enzyme catalysis by serial crystallography
Currently many of the time resolved serial femtosecond (SFX) crystallography experiments are done with light driven protein systems, whereas the reaction initiation for non-light triggered enzymes remains a major bottle neck. Here, the authors present an expanded Drop-on-Tape system, where picoliter-sized droplets of a substrate or inhibitor are turbulently mixed with nanoliter sized droplets of microcrystal slurries, and they use it for time-resolved SFX measurements of inhibitor binding to lysozyme and secondly, binding of a β-lactam antibiotic to a bacterial serine β-lactamase.
- Agata Butryn
- , Philipp S. Simon
- & Allen M. Orville
-
Article
| Open AccessContextualizing genetic risk score for disease screening and rare variant discovery
Genetic studies on complex traits have revealed a substantial role for common, small-effect polygenic burden and large-effect variants. Here, the authors investigate how these types of variation can inform disease risk stratification and prediction.
- Dan Zhou
- , Dongmei Yu
- & Eric R. Gamazon
-
Article
| Open AccessSARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’
Vo’, Italy, is a unique setting for studying SARS-CoV-2 antibody dynamics because mass testing was conducted there early in the pandemic. Here, the authors perform two follow-up serological surveys and estimate seroprevalence, the extent of within-household transmission, and the impact of contact tracing.
- Ilaria Dorigatti
- , Enrico Lavezzo
- & Andrea Crisanti
-
Article
| Open AccessSi-C is a method for inferring super-resolution intact genome structure from single-cell Hi-C data
Constructing valid super-resolution intact genome 3D structures from single-cell Hi-C data is essential in investigating chromosome folding. Here the authors develop a method that makes it possible to visualize and investigate chromosome folding in individual cells at the genome scale
- Luming Meng
- , Chenxi Wang
- & Qiong Luo
-
Article
| Open AccessLineage-specific protection and immune imprinting shape the age distributions of influenza B cases
The earliest infections with influenza A shape the immune responses to future infections, but it is not known if this phenomenon applies to influenza B. Here, the authors use influenza B case data from New Zealand and find evidence for both lineage-specific and imprinting protection.
- Marcos C. Vieira
- , Celeste M. Donato
- & Sarah Cobey
-
Article
| Open AccessAttention-based multi-label neural networks for integrated prediction and interpretation of twelve widely occurring RNA modifications
RNA modifications appear to play a role in determining RNA structure and function. Here, the authors develop a deep learning model that predicts the location of 12 RNA modifications using primary sequence, and show that several modifications are associated, which suggests dependencies between them.
- Zitao Song
- , Daiyun Huang
- & Jia Meng
-
Article
| Open AccessA genetically encoded anti-CRISPR protein constrains gene drive spread and prevents population suppression
Technologies that can halt the spread of gene drives would be highly useful in controlling or reverting their effect. Here the authors use the anti-CRISPR protein AcrIIA4 to inactivate drives in A. gambiae.
- Chrysanthi Taxiarchi
- , Andrea Beaghton
- & Andrea Crisanti
-
Article
| Open AccessSpearheading future omics analyses using dyngen, a multi-modal simulator of single cells
To benchmark single cell bioinformatics tools, data simulators can provide a robust ground truth. Here the authors present dyngen, a multi-modal simulator, and apply it to aligning cell developmental trajectories, cell-specific regulatory network inference and estimation of RNA velocity.
- Robrecht Cannoodt
- , Wouter Saelens
- & Yvan Saeys
-
Article
| Open AccessscGCN is a graph convolutional networks algorithm for knowledge transfer in single cell omics
Making sense of the rapidly growing single-cell omics datasets available is limited by difficulties in leveraging disparate datasets in analyses. Here, the authors present scGCN, a graph based convolutional network to allow effective knowledge transfer across omics datasets.
- Qianqian Song
- , Jing Su
- & Wei Zhang
-
Article
| Open AccessControlling the pandemic during the SARS-CoV-2 vaccination rollout
Despite the consensus that mass vaccination against SARS-CoV-2 will ultimately end the pandemic, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. Here, the authors investigate relaxation scenarios using an age-structured transmission model that has been fitted to data for Portugal.
- João Viana
- , Christiaan H. van Dorp
- & Ganna Rozhnova
-
Article
| Open AccessChildren’s exploratory play tracks the discriminability of hypotheses
People can infer unobserved causes of perceptual data (e.g. the contents of a box from the sound made by shaking it). Here the authors show that children compare what they hear with what they would have heard given other causes, and explore longer when the heard and imagined sounds are hard to discriminate.
- Max H. Siegel
- , Rachel W. Magid
- & Laura E. Schulz
-
Article
| Open AccessMaps and metrics of insecticide-treated net access, use, and nets-per-capita in Africa from 2000-2020
Insecticide treated nets (ITNs) are an important part of malaria control in Africa and WHO targets aim for 80% coverage. This study estimates the spatio-temporal access and use of ITNs in Africa from 2000-2020, and shows that both metrics have improved over time but access remains below WHO targets.
- Amelia Bertozzi-Villa
- , Caitlin A. Bever
- & Samir Bhatt
-
Article
| Open AccessEffect of specific non-pharmaceutical intervention policies on SARS-CoV-2 transmission in the counties of the United States
Disentangling the impacts of non-pharmaceutical interventions on COVID-19 transmission is challenging as they have been used in different combinations across time and space. This study shows that, early in the epidemic, school/daycare closures and stopping nursing home visits were associated with the biggest reduction in transmission in the United States.
- Bingyi Yang
- , Angkana T. Huang
- & Derek A. T. Cummings
-
Article
| Open AccessCitywide serosurveillance of the initial SARS-CoV-2 outbreak in San Francisco using electronic health records
Population-based surveys are the gold standard for estimating seroprevalence but are expensive and often only capture a small geographic area or window of time. This study describes a new platform, SCALE-IT, for serosurveillance based on algorithmic sampling of electronic health records, and uses it to estimate the seroprevalence of SARS-CoV-2 in San Francisco.
- Isobel Routledge
- , Adrienne Epstein
- & Isabel Rodriguez-Barraquer