Abstract:
:Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence-only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth. :Vaccination is the best protection against seasonal flu. It teaches the immune system what the flu virus looks like, preparing it to fight off an infection. But the flu virus changes its molecular appearance every year, escaping the immune defences learnt the year before. So, every year, the vaccine needs updating. Since it takes almost a year to design and make a new flu vaccine, researchers need to be able to predict what flu viruses will look like in the future. Currently, this prediction relies on experiments that assess the molecular appearance of flu viruses, a complex and slow approach. One alternative is to examine the virus's genetic code. Mathematical models try to predict which genetic changes might alter the appearance of a flu virus, saving the cost of performing specialised experiments. Recent research has shown that these models can make good predictions, but including experimental measures of the virus’ appearance could improve them even further. This could help the model to work out which genetic changes are likely to be beneficial to the virus, and which are not. To find out whether experimental data improves model predictions, Huddleston et al. designed a new forecasting tool which used 25 years of historical data from past flu seasons. Each forecast predicted what the virus population might look like the next year using the previous year's genetic code, experimental data, or both. Huddleston et al. then compared the predictions with the historical data to find the most useful data types. This showed that the best predictions combined changes from the virus's genetic code with experimental measures of its appearance. This new forecasting tool is open source, allowing teams across the world to start using it to improve their predictions straight away. Seasonal flu infects between 5 and 15% of the world's population every year, causing between quarter of a million and half a million deaths. Better predictions could lead to better flu vaccines and fewer illnesses and deaths.
journal_name
Elifejournal_title
eLifeauthors
Huddleston J,Barnes JR,Rowe T,Xu X,Kondor R,Wentworth DE,Whittaker L,Ermetal B,Daniels RS,McCauley JW,Fujisaki S,Nakamura K,Kishida N,Watanabe S,Hasegawa H,Barr I,Subbarao K,Barrat-Charlaix P,Neher RA,Bedford Tdoi
10.7554/eLife.60067subject
Has Abstractpub_date
2020-09-02 00:00:00issn
2050-084Xpii
60067journal_volume
9pub_type
杂志文章相关文献
eLife文献大全abstract::Mitochondrial dysfunction is associated with activation of the integrated stress response (ISR) but the underlying triggers remain unclear. We systematically combined acute mitochondrial inhibitors with genetic tools for compartment-specific NADH oxidation to trace mechanisms linking different forms of mitochondrial d...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.49178
更新日期:2020-05-28 00:00:00
abstract::Recent epidemiological and laboratory-based studies suggest that the anti-diabetic drug metformin prevents cancer progression. How metformin diminishes tumor growth is not fully understood. In this study, we report that in human cancer cells, metformin inhibits mitochondrial complex I (NADH dehydrogenase) activity and...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02242
更新日期:2014-05-13 00:00:00
abstract::Temporal patterning of neural progenitors leads to the sequential production of diverse neurons. To understand how extrinsic cues influence intrinsic temporal programs, we studied Drosophila mushroom body progenitors (neuroblasts) that sequentially produce only three neuronal types: γ, then α'β', followed by αβ. Oppos...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.58880
更新日期:2020-07-06 00:00:00
abstract::Understanding the molecular mechanism of glaucoma and development of neuroprotectants is significantly hindered by the lack of a reliable animal model that accurately recapitulates human glaucoma. Here, we sought to develop a mouse model for the secondary glaucoma that is often observed in humans after silicone oil (S...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45881
更新日期:2019-05-15 00:00:00
abstract::Neoangiogenesis is a pivotal therapeutic target in glioblastoma. Tumor monitoring requires imaging methods to assess treatment effects and disease progression. Until now mapping of the tumor vasculature has been difficult. We have developed a combined magnetic resonance and optical toolkit to study neoangiogenesis in ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.11712
更新日期:2016-02-02 00:00:00
abstract::Plasmodium falciparum causes malaria in humans with over 450,000 deaths annually. The asexual blood stage involves invasion of erythrocytes by merozoites, in which they grow and divide to release daughter merozoites, which in turn invade new erythrocytes perpetuating the cycle responsible for malaria. A key step in me...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.21347
更新日期:2017-02-14 00:00:00
abstract::The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.07420
更新日期:2015-07-31 00:00:00
abstract::Meibum lipids form a lipid layer on the outermost side of the tear film and function to prevent water evaporation and reduce surface tension. (O-Acyl)-ω-hydroxy fatty acids (OAHFAs), a subclass of these lipids, are thought to be involved in connecting the lipid and aqueous layers in tears, although their actual functi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.53582
更新日期:2020-04-07 00:00:00
abstract::Vitamin B12 (cobalamin) is the most complex B-type vitamin and is synthetized exclusively in a limited number of prokaryotes. Its biologically active variants contain rare organometallic bonds, which are used by enzymes in a variety of central metabolic pathways such as L-methionine synthesis and ribonucleotide reduct...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.35828
更新日期:2018-05-29 00:00:00
abstract::Toothed whales use sonar to detect, locate, and track prey. They adjust emitted sound intensity, auditory sensitivity and click rate to target range, and terminate prey pursuits with high-repetition-rate, low-intensity buzzes. However, their narrow acoustic field of view (FOV) is considered stable throughout target ap...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05651
更新日期:2015-03-20 00:00:00
abstract::Dedifferentiation of acini to duct-like cells occurs during the physiologic damage response in the pancreas, but this process can be co-opted by oncogenic Kras to drive carcinogenesis. Myeloid cells infiltrate the pancreas during the onset of pancreatic cancer, and promote carcinogenesis. Here, we show that the functi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.27388
更新日期:2017-10-05 00:00:00
abstract::Cell growth and/or proliferation may require the reprogramming of metabolic pathways, whereby a switch from oxidative to glycolytic metabolism diverts glycolytic intermediates towards anabolic pathways. Herein, we identify a novel role for TRIM32 in the maintenance of glycolytic flux mediated by biochemical interactio...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.52358
更新日期:2020-03-30 00:00:00
abstract::Genetic techniques have shed new light on the organization of the neurons in the ventral nervous system of the fruit fly. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.10317
更新日期:2015-08-28 00:00:00
abstract::During outbreaks of high-consequence pathogens, airport screening programs have been deployed to curtail geographic spread of infection. The effectiveness of screening depends on several factors, including pathogen natural history and epidemiology, human behavior, and characteristics of the source epidemic. We develop...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.05564
更新日期:2015-02-19 00:00:00
abstract::Macrophage-mediated phagocytosis and cytokine production represent the front lines of resistance to bacterial invaders. A key feature of this pro-inflammatory response in mammals is the complex remodeling of cellular metabolism towards aerobic glycolysis. Although the function of bactericidal macrophages is highly con...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.50414
更新日期:2019-10-14 00:00:00
abstract::Burkholderia thailandensis uses acyl-homoserine lactone-mediated quorum sensing systems to regulate hundreds of genes. Here we show that cell-cell contact-dependent type VI secretion (T6S) toxin-immunity systems are among those activated by quorum sensing in B. thailandensis. We also demonstrate that T6S is required t...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.14712
更新日期:2016-05-16 00:00:00
abstract::As the staff of the MRC Laboratory of Molecular Biology settle into their new building in Cambridge, its director Hugh Pelham explains the challenges of living up to its prestigious past. ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.00856
更新日期:2013-05-28 00:00:00
abstract::Aedes aegypti transmit pathogenic arboviruses while the mosquito itself tolerates the infection. We examine a piRNA-based immunity that relies on the acquisition of viral derived cDNA (vDNA) and how this pathway discriminates between self and non-self. The piRNAs derived from these vDNAs are essential for virus contro...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.41244
更新日期:2019-10-17 00:00:00
abstract::Early mouse development is accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2), which is essential for embryonic development. Here we show that genome-wide accumulation of H3K9me2 is crucial for postimplantation development, and coincides with r...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.09571
更新日期:2015-11-09 00:00:00
abstract::Current models successfully describe the auditory cortical response to natural sounds with a set of spectro-temporal features. However, these models have hardly been linked to the ill-understood neurobiological changes that occur in the aging auditory cortex. Modelling the hemodynamic response to a rich natural sound ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.55300
更新日期:2020-07-03 00:00:00
abstract::Whether somatic mutations contribute functional diversity to brain cells is a long-standing question. Single-neuron genomics enables direct measurement of somatic mutation rates in human brain and promises to answer this question. A recent study (Upton et al., 2015) reported high rates of somatic LINE-1 element (L1) r...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.12966
更新日期:2016-02-22 00:00:00
abstract::The restoration of homeostasis after tissue damage relies on proper spatial-temporal control of damage-induced apoptosis and compensatory proliferation. In Drosophila imaginal discs these processes are coordinated by the stress response pathway JNK. We demonstrate that JNK signaling induces a dose-dependent extension ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.41036
更新日期:2019-02-08 00:00:00
abstract::Ten countries have reported pfhrp2/pfhrp3 gene deletions since the first observation of pfhrp2-deleted parasites in 2012. In a previous study (Watson et al., 2017), we characterised the drivers selecting for pfhrp2/3 deletions and mapped the regions in Africa with the greatest selection pressure. In February 2018, the...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.40339
更新日期:2019-05-02 00:00:00
abstract::Feedback inhibitory motifs are thought to be important for pattern separation across species. How feedback circuits may implement pattern separation of biologically plausible, temporally structured input in mammals is, however, poorly understood. We have quantitatively determined key properties of netfeedback inhibiti...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.53148
更新日期:2020-02-20 00:00:00
abstract::When a plant cell divides, four related proteins control the trafficking of vesicles and ensure that cargo that is normally recycled to the plasma membrane is instead re-routed to the plane of cell division. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.02747
更新日期:2014-04-08 00:00:00
abstract::White adipose tissue (WAT) inflammation contributes to the development of insulin resistance in obesity. While the role of adipose tissue macrophage (ATM) pro-inflammatory signalling in the development of insulin resistance has been established, it is less clear how WAT inflammation is initiated. Here, we show that AT...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47990
更新日期:2019-08-16 00:00:00
abstract::Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. Perfori...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.06508
更新日期:2015-09-24 00:00:00
abstract::To effectively interact with their environment, humans must often select actions from multiple incompatible options. Existing theories propose that during motoric response-conflict, inappropriate motor activity is actively (and perhaps non-selectively) suppressed by an inhibitory fronto-basal ganglia mechanism. We her...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.42959
更新日期:2019-05-07 00:00:00
abstract::We previously showed in Drosophila melanogaster embryos that low-affinity Ultrabithorax (Ubx)-responsive shavenbaby (svb) enhancers drive expression using localized transcriptional environments and that active svb enhancers on different chromosomes tended to colocalize (Tsai et al., 2017). Here, we test the hypothesis...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45325
更新日期:2019-07-11 00:00:00
abstract::Hair follicle (HF) development is orchestrated by coordinated signals from adjacent epithelial and mesenchymal cells. In humans this process only occurs during embryogenesis and viable strategies to induce new HFs in adult skin are lacking. Here, we reveal that activation of Hedgehog (Hh) signaling in adjacent epithel...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.46756
更新日期:2020-03-17 00:00:00