scholarly journals Metaviromic identification of genetic hotspots of coronavirus pathogenicity using machine learning

2020 ◽  
Author(s):  
Jonathan J. Park ◽  
Sidi Chen

AbstractThe COVID-19 pandemic caused by SARS-CoV-2 has become a major threat across the globe. Here, we developed machine learning approaches to identify key pathogenic regions in coronavirus genomes. We trained and evaluated 7,562,625 models on 3,665 genomes including SARS-CoV-2, MERS-CoV, SARS-CoV and other coronaviruses of human and animal origins to return quantitative and biologically interpretable signatures at nucleotide and amino acid resolutions. We identified hotspots across the SARS-CoV-2 genome including previously unappreciated features in spike, RdRp and other proteins. Finally, we integrated pathogenicity genomic profiles with B cell and T cell epitope predictions for enrichment of sequence targets to help guide vaccine development. These results provide a systematic map of predicted pathogenicity in SARS-CoV-2 that incorporates sequence, structural and immunological features, providing an unbiased collection of genetic elements for functional studies. This metavirome-based framework can also be applied for rapid characterization of new coronavirus strains or emerging pathogenic viruses.

Author(s):  
Jeffrey G Klann ◽  
Griffin M Weber ◽  
Hossein Estiri ◽  
Bertrand Moal ◽  
Paul Avillach ◽  
...  

AbstractIntroductionThe Consortium for Clinical Characterization of COVID-19 by EHR (4CE) includes hundreds of hospitals internationally using a federated computational approach to COVID-19 research using the EHR.ObjectiveWe sought to develop and validate a standard definition of COVID-19 severity from readily accessible EHR data across the Consortium.MethodsWe developed an EHR-based severity algorithm and validated it on patient hospitalization data from 12 4CE clinical sites against the outcomes of ICU admission and/or death. We also used a machine learning approach to compare selected predictors of severity to the 4CE algorithm at one site.ResultsThe 4CE severity algorithm performed with pooled sensitivity of 0.73 and specificity 0.83 for the combined outcome of ICU admission and/or death. The sensitivity of single code categories for acuity were unacceptably inaccurate - varying by up to 0.65 across sites. A multivariate machine learning approach identified codes resulting in mean AUC 0.956 (95% CI: 0.952, 0.959) compared to 0.903 (95% CI: 0.886, 0.921) using expert-derived codes. Billing codes were poor proxies of ICU admission, with 49% precision and recall compared against chart review at one partner institution.DiscussionWe developed a proxy measure of severity that proved resilient to coding variability internationally by using a set of 6 code classes. In contrast, machine-learning approaches may tend to overfit hospital-specific orders. Manual chart review revealed discrepancies even in the gold standard outcomes, possibly due to pandemic conditions.ConclusionWe developed an EHR-based algorithm for COVID-19 severity and validated it at 12 international sites.


2017 ◽  
Vol 106 (11) ◽  
pp. 3270-3279 ◽  
Author(s):  
Maulik K. Nariya ◽  
Jae Hyun Kim ◽  
Jian Xiong ◽  
Peter A. Kleindl ◽  
Asha Hewarathna ◽  
...  

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
John P. Haran ◽  
Shakti K. Bhattarai ◽  
Sage E. Foley ◽  
Protiva Dutta ◽  
Doyle V. Ward ◽  
...  

ABSTRACT The microbiota-gut-brain axis is a bidirectional communication system that is poorly understood. Alzheimer’s disease (AD), the most common cause of dementia, has long been associated with bacterial infections and inflammation-causing immunosenescence. Recent studies examining the intestinal microbiota of AD patients revealed that their microbiome differs from that of subjects without dementia. In this work, we prospectively enrolled 108 nursing home elders and followed each for up to 5 months, collecting longitudinal stool samples from which we performed metagenomic sequencing and in vitro T84 intestinal epithelial cell functional assays for P-glycoprotein (P-gp) expression, a critical mediator of intestinal homeostasis. Our analysis identified clinical parameters as well as numerous microbial taxa and functional genes that act as predictors of AD dementia in comparison to elders without dementia or with other dementia types. We further demonstrate that stool samples from elders with AD can induce lower P-gp expression levels in vitro those samples from elders without dementia or with other dementia types. We also paired functional studies with machine learning approaches to identify bacterial species differentiating the microbiome of AD elders from that of elders without dementia, which in turn are accurate predictors of the loss of dysregulation of the P-gp pathway. We observed that the microbiome of AD elders shows a lower proportion and prevalence of bacteria with the potential to synthesize butyrate, as well as higher abundances of taxa that are known to cause proinflammatory states. Therefore, a potential nexus between the intestinal microbiome and AD is the modulation of intestinal homeostasis by increases in inflammatory, and decreases in anti-inflammatory, microbial metabolism. IMPORTANCE Studies of the intestinal microbiome and AD have demonstrated associations with microbiome composition at the genus level among matched cohorts. We move this body of literature forward by more deeply investigating microbiome composition via metagenomics and by comparing AD patients against those without dementia and with other dementia types. We also exploit machine learning approaches that combine both metagenomic and clinical data. Finally, our functional studies using stool samples from elders demonstrate how the c microbiome of AD elders can affect intestinal health via dysregulation of the P-glycoprotein pathway. P-glycoprotein dysregulation contributes directly to inflammatory disorders of the intestine. Since AD has been long thought to be linked to chronic bacterial infections as a possible etiology, our findings therefore fill a gap in knowledge in the field of AD research by identifying a nexus between the microbiome, loss of intestinal homeostasis, and inflammation that may underlie this neurodegenerative disorder.


2020 ◽  
Vol 6 ◽  
pp. e313
Author(s):  
Haruna Chiroma ◽  
Absalom E. Ezugwu ◽  
Fatsuma Jauro ◽  
Mohammed A. Al-Garadi ◽  
Idris N. Abdullahi ◽  
...  

Background and Objective The COVID-19 pandemic has caused severe mortality across the globe, with the USA as the current epicenter of the COVID-19 epidemic even though the initial outbreak was in Wuhan, China. Many studies successfully applied machine learning to fight COVID-19 pandemic from a different perspective. To the best of the authors’ knowledge, no comprehensive survey with bibliometric analysis has been conducted yet on the adoption of machine learning to fight COVID-19. Therefore, the main goal of this study is to bridge this gap by carrying out an in-depth survey with bibliometric analysis on the adoption of machine learning-based technologies to fight COVID-19 pandemic from a different perspective, including an extensive systematic literature review and bibliometric analysis. Methods We applied a literature survey methodology to retrieved data from academic databases and subsequently employed a bibliometric technique to analyze the accessed records. Besides, the concise summary, sources of COVID-19 datasets, taxonomy, synthesis and analysis are presented in this study. It was found that the Convolutional Neural Network (CNN) is mainly utilized in developing COVID-19 diagnosis and prognosis tools, mostly from chest X-ray and chest CT scan images. Similarly, in this study, we performed a bibliometric analysis of machine learning-based COVID-19 related publications in the Scopus and Web of Science citation indexes. Finally, we propose a new perspective for solving the challenges identified as direction for future research. We believe the survey with bibliometric analysis can help researchers easily detect areas that require further development and identify potential collaborators. Results The findings of the analysis presented in this article reveal that machine learning-based COVID-19 diagnose tools received the most considerable attention from researchers. Specifically, the analyses of results show that energy and resources are more dispenses towards COVID-19 automated diagnose tools while COVID-19 drugs and vaccine development remains grossly underexploited. Besides, the machine learning-based algorithm that is predominantly utilized by researchers in developing the diagnostic tool is CNN mainly from X-rays and CT scan images. Conclusions The challenges hindering practical work on the application of machine learning-based technologies to fight COVID-19 and new perspective to solve the identified problems are presented in this article. Furthermore, we believed that the presented survey with bibliometric analysis could make it easier for researchers to identify areas that need further development and possibly identify potential collaborators at author, country and institutional level, with the overall aim of furthering research in the focused area of machine learning application to disease control.


Author(s):  
Chen Wei ◽  
Mingkai Chen ◽  
Wenying Deng ◽  
Liangyu Bie ◽  
Yijie Ma ◽  
...  

Abstract Cancer stem cells (CSCs) actively reprogram their tumor microenvironment (TME) to sustain a supportive niche, which may have a dramatic impact on prognosis and immunotherapy. However, our knowledge of the landscape of the gastric cancer stem-like cell (GCSC) microenvironment needs to be further improved. A multi-step process of machine learning approaches was performed to develop and validate the prognostic and predictive potential of the GCSC-related score (GCScore). The high GCScore subgroup was not only associated with stem cell characteristics, but also with a potential immune escape mechanism. Furthermore, we experimentally demonstrated the upregulated infiltration of CD206+ tumor-associated macrophages (TAMs) in the invasive margin region, which in turn maintained the stem cell properties of tumor cells. Finally, we proposed that the GCScore showed a robust capacity for prediction for immunotherapy, and investigated potential therapeutic targets and compounds for patients with a high GCScore. The results indicate that the proposed GCScore can be a promising predictor of prognosis and responses to immunotherapy, which provides new strategies for the precision treatment of GCSCs.


2019 ◽  
Vol 4 (1) ◽  
pp. 1-7
Author(s):  
Gerardo M. Casañola-Martin ◽  
Hai Pham-The

The development of machine learning algorithms together with the availability of computational tools nowadays have given an increase in the application of artificial intelligence methodologies in different fields. However, the use of these machine learning approaches in nanomedicine remains still underexplored in certain areas, despite the development in hardware and software tools. In this review, the recent advances in the conjunction of machine learning with nanomedicine are shown. Examples dealing with biomedical properties of nanoparticles, characterization of nanomaterials, text mining, and image analysis are also presented. Finally, some future perspectives in the integration of nanomedicine with cloud computing, deep learning and other techniques are discussed.


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