传染病建模(英文)最新文献

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Understanding the transmission pathways of Lassa fever: A mathematical modeling approach 了解拉沙热的传播途径:数学建模方法
传染病建模(英文) Pub Date : 2022-09-23 DOI: 10.1101/2022.09.19.22280113
P. Madueme, F. Chirove
{"title":"Understanding the transmission pathways of Lassa fever: A mathematical modeling approach","authors":"P. Madueme, F. Chirove","doi":"10.1101/2022.09.19.22280113","DOIUrl":"https://doi.org/10.1101/2022.09.19.22280113","url":null,"abstract":"The spread of Lassa fever infection is increasing in West Africa over the last decade. The impact of this can better be understood when considering the various possible transmission routes. We designed a mathematical model for the epidemiology of Lassa Fever using a system of nonlinear ordinary differential equations to determine the effect of transmission pathways toward the infection progression in humans and rodents including those usually neglected. We analyzed the model and carried out numerical simulations to determine the impact of each of the transmission routes. Our results showed that the burden of Lassa fever infection is increased when all the transmission routes are incorporated and most single transmission routes are less harmful, but when in combination with other transmission routes, they increase the Lassa fever burden. It is therefore important to consider multiple transmission routes to better estimate the Lassa fever burden optimally and in turn determine control strategies targeted at the transmission pathways.","PeriodicalId":64814,"journal":{"name":"传染病建模(英文)","volume":"8 1","pages":"27 - 57"},"PeriodicalIF":0.0,"publicationDate":"2022-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49100073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Improving estimates of waning immunity rates in stochastic SIRS models with a hierarchical framework 用分层框架改进随机SIRS模型中免疫下降率的估计
传染病建模(英文) Pub Date : 2022-09-17 DOI: 10.1101/2022.09.14.22279950
P. Alahakoon, J. McCaw, P. Taylor
{"title":"Improving estimates of waning immunity rates in stochastic SIRS models with a hierarchical framework","authors":"P. Alahakoon, J. McCaw, P. Taylor","doi":"10.1101/2022.09.14.22279950","DOIUrl":"https://doi.org/10.1101/2022.09.14.22279950","url":null,"abstract":"Most disease pathogens require onward transmission for their continued persistence. It is necessary to have continuous replenishment of the population of susceptibles, either through births, immigration, or waning immunity in recovered individuals. Consider the introduction of an unknown infectious disease into a fully susceptible population where it is not known how long immunity is conferred once an individual recovers. If the disease takes off, the number of infectives will typically decrease to a low level after the first major outbreak. During this period, the disease dynamics will be highly influenced by stochastic effects and there is a non-zero probability that the epidemic will die out. This is known as an epidemic fade-out. If the disease does not die out, the susceptible population may be replenished by the waning of immunity, and a second wave may start. In this study, we describe an experiment where we generated synthetic outbreak data from independent stochastic SIRS models in multiple communities. Some of the outbreaks faded-out and some did not. By conducting Bayesian parameter estimation independently on each outbreak, as well as under a hierarchical framework, we investigated if the waning immunity rate could be correctly identified. When the outbreaks were considered independently, the waning immunity rate was incorrectly estimated when an epidemic fade-out was observed. However, the hierarchical approach improved the parameter estimates. This was particularly the case for those communities where the epidemic faded out.","PeriodicalId":64814,"journal":{"name":"传染病建模(英文)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49107111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
The impact of age structure and vaccine prioritization on COVID-19 in West Africa 西非年龄结构和疫苗重点对COVID-19的影响
传染病建模(英文) Pub Date : 2022-07-05 DOI: 10.1101/2022.07.03.22277195
H. B. Taboe, M. Asare-Baah, Afsana Yesmin, C. Ngonghala
{"title":"The impact of age structure and vaccine prioritization on COVID-19 in West Africa","authors":"H. B. Taboe, M. Asare-Baah, Afsana Yesmin, C. Ngonghala","doi":"10.1101/2022.07.03.22277195","DOIUrl":"https://doi.org/10.1101/2022.07.03.22277195","url":null,"abstract":"\u0000 The ongoing COVID-19 pandemic has been a major global health challenge since its emergence in 2019. Contrary to early predictions that sub-Saharan Africa (SSA) would bear a disproportionate share of the burden of COVID-19 due to the region's vulnerability to other infectious diseases, weak healthcare systems, and socioeconomic conditions, the pandemic's effects in SSA have been very mild in comparison to other regions. Interestingly, the number of cases, hospitalizations, and disease-induced deaths in SSA remain low, despite the loose implementation of non-pharmaceutical interventions (NPIs) and the low availability and administration of vaccines. Possible explanations for this low burden include epidemiological disparities, under-reporting (due to limited testing), climatic factors, population structure, and government policy initiatives. In this study, we formulate a model framework consisting of a basic model (in which only susceptible individuals are vaccinated), a vaccine-structured model, and a hybrid vaccine-age-structured model to assess the dynamics of COVID-19 in West Africa (WA). The framework is trained with a portion of the confirmed daily COVID-19 case data for 16 West African countries, validated with the remaining portion of the data, and used to (i) assess the effect of age structure on the incidence of COVID-19 in WA, (ii) evaluate the impact of vaccination and vaccine prioritization based on age brackets on the burden of COVID-19 in the sub-region, and (iii) explore plausible reasons for the low burden of COVID-19 in WA compared to other parts of the world. Calibration of the model parameters and global sensitivity analysis show that asymptomatic youths are the primary drivers of the pandemic in WA. Also, the basic and control reproduction numbers of the hybrid vaccine-age-structured model are smaller than those of the other two models indicating that the disease burden is overestimated in the models which do not account for age-structure. This result is also confirmed through the vaccine-derived herd immunity thresholds. In particular, a comprehensive analysis of the basic (vaccine-structured) model reveals that if 84%(73%) of the West African populace is fully immunized with the vaccines authorized for use in WA, vaccine-derived herd immunity can be achieved. This herd immunity threshold is lower (68%) for the hybrid model. Also, all three thresholds are lower (60% for the basic model, 51% for the vaccine-structured model, and 48% for the hybrid model) if vaccines of higher efficacies (e.g., the Pfizer or Moderna vaccine) are prioritized, and higher if vaccines of lower efficacy are prioritized. Simulations of the models show that controlling the COVID-19 pandemic in WA (by reducing transmission) requires a proactive approach, including prioritizing vaccination of more youths or vaccination of more youths and elderly simultaneously. Moreover, complementing vaccination with a higher level of mask compliance will improve the ","PeriodicalId":64814,"journal":{"name":"传染病建模(英文)","volume":"7 1","pages":"709 - 727"},"PeriodicalIF":0.0,"publicationDate":"2022-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44583310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Clarifying predictions for COVID-19 from testing data: The example of New York State 从检测数据中阐明对COVID-19的预测:以纽约州为例
传染病建模(英文) Pub Date : 2020-10-12 DOI: 10.1101/2020.10.10.20203034
Q. Griette, Pierre Magal
{"title":"Clarifying predictions for COVID-19 from testing data: The example of New York State","authors":"Q. Griette, Pierre Magal","doi":"10.1101/2020.10.10.20203034","DOIUrl":"https://doi.org/10.1101/2020.10.10.20203034","url":null,"abstract":"\u0000 With the spread of COVID-19 across the world, a large amount of data on reported cases has become available. We are studying here a potential bias induced by the daily number of tests which may be insufficient or vary over time. Indeed, tests are hard to produce at the early stage of the epidemic and can therefore be a limiting factor in the detection of cases. Such a limitation may have a strong impact on the reported cases data. Indeed, some cases may be missing from the official count because the number of tests was not sufficient on a given day. In this work, we propose a new differential equation epidemic model which uses the daily number of tests as an input. We obtain a good agreement between the model simulations and the reported cases data coming from the state of New York. We also explore the relationship between the dynamic of the number of tests and the dynamics of the cases. We obtain a good match between the data and the outcome of the model. Finally, by multiplying the number of tests by 2, 5, 10, and 100 we explore the consequences for the number of reported cases.\u0000","PeriodicalId":64814,"journal":{"name":"传染病建模(英文)","volume":"6 1","pages":"273 - 283"},"PeriodicalIF":0.0,"publicationDate":"2020-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48468622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
On the reliability of predictions on Covid-19 dynamics: A systematic and critical review of modelling techniques 关于新冠肺炎动态预测的可靠性:对建模技术的系统和批判性回顾
传染病建模(英文) Pub Date : 2020-09-11 DOI: 10.1101/2020.09.10.20192328
J. Gnanvi, K. V. Salako, Gaëtan Brezesky Kotanmi, R. G. Glèlè Kakaï
{"title":"On the reliability of predictions on Covid-19 dynamics: A systematic and critical review of modelling techniques","authors":"J. Gnanvi, K. V. Salako, Gaëtan Brezesky Kotanmi, R. G. Glèlè Kakaï","doi":"10.1101/2020.09.10.20192328","DOIUrl":"https://doi.org/10.1101/2020.09.10.20192328","url":null,"abstract":"\u0000 Since the emergence of the novel 2019 coronavirus pandemic in December 2019 (COVID-19), numerous modellers have used diverse techniques to assess the dynamics of transmission of the disease, predict its future course and determine the impact of different control measures. In this study, we conducted a global systematic literature review to summarize trends in the modelling techniques used for Covid-19 from January 1st, 2020 to October 30th, 2020. We further examined the reliability and correctness of predictions by comparing predicted and observed values for cumulative cases and deaths. From an initial 4311 peer-reviewed articles and preprints found with our defined keywords, 242 were fully analysed. Most studies were done on Asian (46.52%) and European (27.39%) countries. Most of them used compartmental models (namely SIR and SEIR) (46.1%) and statistical models (growth models and time series) (31.8%) while few used artificial intelligence (6.7%), Bayesian approach (4.7%), Network models (2.3%) and Agent-based models (1.3%). For the number of cumulative cases, the ratio of the predicted over the observed values and the ratio of the amplitude of confidence interval (CI) or credibility interval (CrI) of predictions and the central value were on average larger than 1 indicating cases of inaccurate and imprecise predictions, and large variation across predictions. There was no clear difference among models used for these two ratios. In 75% of predictions that provided CI or CrI, observed values fall within the 95% CI or CrI of the cumulative cases predicted. Only 3.7% of the studies predicted the cumulative number of deaths. For 70% of the predictions, the ratio of predicted over observed cumulative deaths was less or close to 1. Also, the Bayesian model made predictions closer to reality than classical statistical models, although these differences are only suggestive due to the small number of predictions within our dataset (9 in total). In addition, we found a significant negative correlation (rho = - 0.56, p = 0.021) between this ratio and the length (in days) of the period covered by the modelling, suggesting that the longer the period covered by the model the likely more accurate the estimates tend to be. Our findings suggest that while predictions made by the different models are useful to understand the pandemic course and guide policy-making, some were relatively accurate and precise while other not.\u0000","PeriodicalId":64814,"journal":{"name":"传染病建模(英文)","volume":"6 1","pages":"258 - 272"},"PeriodicalIF":0.0,"publicationDate":"2020-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41508496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 69
Identifying the measurements required to estimate rates of COVID-19 transmission, infection, and detection, using variational data assimilation 使用变分数据同化,确定估计新冠肺炎传播、感染和检测率所需的测量
传染病建模(英文) Pub Date : 2020-05-25 DOI: 10.1101/2020.05.27.20112987
Eve Armstrong, Manuela Runge, J. Gerardin
{"title":"Identifying the measurements required to estimate rates of COVID-19 transmission, infection, and detection, using variational data assimilation","authors":"Eve Armstrong, Manuela Runge, J. Gerardin","doi":"10.1101/2020.05.27.20112987","DOIUrl":"https://doi.org/10.1101/2020.05.27.20112987","url":null,"abstract":"\u0000 We demonstrate the ability of statistical data assimilation (SDA) to identify the measurements required for accurate state and parameter estimation in an epidemiological model for the novel coronavirus disease COVID-19. Our context is an effort to inform policy regarding social behavior, to mitigate strain on hospital capacity. The model unknowns are taken to be: the time-varying transmission rate, the fraction of exposed cases that require hospitalization, and the time-varying detection probabilities of new asymptomatic and symptomatic cases. In simulations, we obtain estimates of undetected (that is, unmeasured) infectious populations, by measuring the detected cases together with the recovered and dead - and without assumed knowledge of the detection rates. Given a noiseless measurement of the recovered population, excellent estimates of all quantities are obtained using a temporal baseline of 101 days, with the exception of the time-varying transmission rate at times prior to the implementation of social distancing. With low noise added to the recovered population, accurate state estimates require a lengthening of the temporal baseline of measurements. Estimates of all parameters are sensitive to the contamination, highlighting the need for accurate and uniform methods of reporting. The aim of this paper is to exemplify the power of SDA to determine what properties of measurements will yield estimates of unknown parameters to a desired precision, in a model with the complexity required to capture important features of the COVID-19 pandemic.\u0000","PeriodicalId":64814,"journal":{"name":"传染病建模(英文)","volume":"6 1","pages":"133 - 147"},"PeriodicalIF":0.0,"publicationDate":"2020-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45990187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Will an imperfect vaccine curtail the COVID-19 pandemic in the U.S.? 不完善的疫苗能否遏制美国的COVID-19大流行?
传染病建模(英文) Pub Date : 2020-05-14 DOI: 10.1101/2020.05.10.20097428
E. Iboi, C. Ngonghala, A. Gumel
{"title":"Will an imperfect vaccine curtail the COVID-19 pandemic in the U.S.?","authors":"E. Iboi, C. Ngonghala, A. Gumel","doi":"10.1101/2020.05.10.20097428","DOIUrl":"https://doi.org/10.1101/2020.05.10.20097428","url":null,"abstract":"\u0000 Abstract\u0000 \u0000 The novel coronavirus (COVID-19) that emerged from Wuhan city of China in late December 2019 continue to pose devastating public health and economic challenges across the world. Although the community-wide implementation of basic non-pharmaceutical intervention measures, such as social distancing, quarantine of suspected COVID-19 cases, isolation of confirmed cases, use of face masks in public, contact tracing and testing, have been quite effective in curtailing and mitigating the burden of the pandemic, it is universally believed that the use of a vaccine may be necessary to effectively curtail and eliminating COVID-19 in human populations. This study is based on the use of a mathematical model for assessing the impact of a hypothetical imperfect anti-COVID-19 vaccine on the control of COVID-19 in the United States. An analytical expression for the minimum percentage of unvaccinated susceptible individuals needed to be vaccinated in order to achieve vaccine-induced community herd immunity is derived. The epidemiological consequence of the herd immunity threshold is that the disease can be effectively controlled or eliminated if the minimum herd immunity threshold is achieved in the community. Simulations of the model, using baseline parameter values obtained from fitting the model with COVID-19 mortality data for the U.S., show that, for an anti-COVID-19 vaccine with an assumed protective efficacy of 80%, at least 82% of the susceptible US population need to be vaccinated to achieve the herd immunity threshold. The prospect of COVID-19 elimination in the US, using the hypothetical vaccine, is greatly enhanced if the vaccination program is combined with other interventions, such as face mask usage and/or social distancing. Such combination of strategies significantly reduces the level of the vaccine-induced herd immunity threshold needed to eliminate the pandemic in the US. For instance, the herd immunity threshold decreases to 72% if half of the US population regularly wears face masks in public (the threshold decreases to 46% if everyone wears a face mask).\u0000 \u0000","PeriodicalId":64814,"journal":{"name":"传染病建模(英文)","volume":"5 1","pages":"510 - 524"},"PeriodicalIF":0.0,"publicationDate":"2020-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46797079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 160
Estimative of real number of infections by COVID-19 in Brazil and possible scenarios 巴西COVID-19实际感染人数的估计和可能的情况
传染病建模(英文) Pub Date : 2020-05-08 DOI: 10.1101/2020.05.03.20052779
P. H. Cintra, Felipe Fontinele Nunes
{"title":"Estimative of real number of infections by COVID-19 in Brazil and possible scenarios","authors":"P. H. Cintra, Felipe Fontinele Nunes","doi":"10.1101/2020.05.03.20052779","DOIUrl":"https://doi.org/10.1101/2020.05.03.20052779","url":null,"abstract":"\u0000 This paper attempts to provide methods to estimate the real scenario of the novel coronavirus pandemic in Brazil, specifically in the states of Sao Paulo, Pernambuco, Espirito Santo, Amazonas and the Federal District. By the use of a SEIRD mathematical model with age division, we predict the infection and death curves, stating the peak date for Brazil and above states. We also carry out a prediction for the ICU demand in these states and for how severe possible collapse in the local health system would be. Finally, we establish some future scenarios including the relaxation on social isolation and the introduction of vaccines and other efficient therapeutic treatments against the virus.\u0000","PeriodicalId":64814,"journal":{"name":"传染病建模(英文)","volume":"5 1","pages":"720 - 736"},"PeriodicalIF":0.0,"publicationDate":"2020-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41391395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
Targeted adaptive isolation strategy for COVID-19 pandemic 针对COVID-19大流行的定向适应性隔离策略
传染病建模(英文) Pub Date : 2020-03-31 DOI: 10.1101/2020.03.23.20041897
Z. Neufeld, H. Khataee, A. Czirók
{"title":"Targeted adaptive isolation strategy for COVID-19 pandemic","authors":"Z. Neufeld, H. Khataee, A. Czirók","doi":"10.1101/2020.03.23.20041897","DOIUrl":"https://doi.org/10.1101/2020.03.23.20041897","url":null,"abstract":"\u0000 Abstract\u0000 \u0000 We investigate the effects of social distancing in controlling the impact of the COVID-19 epidemic using a simple susceptible-infected-removed epidemic model. We show that an alternative or complementary approach based on targeted isolation of the vulnerable sub-population may provide a more efficient and robust strategy at a lower economic and social cost within a shorter timeframe resulting in a collectively immune population.\u0000 \u0000 ","PeriodicalId":64814,"journal":{"name":"传染病建模(英文)","volume":"5 1","pages":"357 - 361"},"PeriodicalIF":0.0,"publicationDate":"2020-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47788188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 34
BCL-2 system analysis identifies high-risk colorectal cancer patients. BCL-2系统分析可识别高风险结直肠癌患者。
IF 24.5
传染病建模(英文) Pub Date : 2017-12-01 Epub Date: 2016-09-23 DOI: 10.1136/gutjnl-2016-312287
Andreas U Lindner, Manuela Salvucci, Clare Morgan, Naser Monsefi, Alexa J Resler, Mattia Cremona, Sarah Curry, Sinead Toomey, Robert O'Byrne, Orna Bacon, Michael Stühler, Lorna Flanagan, Richard Wilson, Patrick G Johnston, Manuel Salto-Tellez, Sophie Camilleri-Broët, Deborah A McNamara, Elaine W Kay, Bryan T Hennessy, Pierre Laurent-Puig, Sandra Van Schaeybroeck, Jochen H M Prehn
{"title":"BCL-2 system analysis identifies high-risk colorectal cancer patients.","authors":"Andreas U Lindner, Manuela Salvucci, Clare Morgan, Naser Monsefi, Alexa J Resler, Mattia Cremona, Sarah Curry, Sinead Toomey, Robert O'Byrne, Orna Bacon, Michael Stühler, Lorna Flanagan, Richard Wilson, Patrick G Johnston, Manuel Salto-Tellez, Sophie Camilleri-Broët, Deborah A McNamara, Elaine W Kay, Bryan T Hennessy, Pierre Laurent-Puig, Sandra Van Schaeybroeck, Jochen H M Prehn","doi":"10.1136/gutjnl-2016-312287","DOIUrl":"10.1136/gutjnl-2016-312287","url":null,"abstract":"<p><strong>Objective: </strong>The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC).</p><p><strong>Design: </strong>Absolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC. We applied DR_MOMP to categorise patients as high or low risk based on model outputs, and compared model outputs with known prognostic factors (T-stage, N-stage, lymphovascular invasion). DR_MOMP signatures were validated on protein of n=156 patients with CRC from the Cancer Genome Atlas (TCGA) project.</p><p><strong>Results: </strong>High-risk stage III patients identified by DR_MOMP had an approximately fivefold increased risk of death compared with patients identified as low risk (HR 5.2, 95% CI 1.4 to 17.9, p=0.02). The DR_MOMP signature ranked highest among all molecular and pathological features analysed. The prognostic signature was validated in the TCGA colon adenocarcinoma (COAD) cohort (HR 4.2, 95% CI 1.1 to 15.6, p=0.04). DR_MOMP also further stratified patients identified by supervised gene expression risk scores into low-risk and high-risk categories. BCL-2-dependent signalling critically contributed to treatment responses in consensus molecular subtypes 1 and 3, linking for the first time specific molecular subtypes to apoptosis signalling.</p><p><strong>Conclusions: </strong>DR_MOMP delivers a system-based biomarker with significant potential as a prognostic tool for stage III CRC that significantly improves established histopathological risk factors.</p>","PeriodicalId":64814,"journal":{"name":"传染病建模(英文)","volume":"7 1","pages":"2141-2148"},"PeriodicalIF":24.5,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64170904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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