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1.
Front Microbiol ; 13: 842976, 2022.
Article in English | MEDLINE | ID: covidwho-1825493

ABSTRACT

Identifying human-virus protein-protein interactions (PPIs) is an essential step for understanding viral infection mechanisms and antiviral response of the human host. Recent advances in high-throughput experimental techniques enable the significant accumulation of human-virus PPI data, which have further fueled the development of machine learning-based human-virus PPI prediction methods. Emerging as a very promising method to predict human-virus PPIs, deep learning shows the powerful ability to integrate large-scale datasets, learn complex sequence-structure relationships of proteins and convert the learned patterns into final prediction models with high accuracy. Focusing on the recent progresses of deep learning-powered human-virus PPI predictions, we review technical details of these newly developed methods, including dataset preparation, deep learning architectures, feature engineering, and performance assessment. Moreover, we discuss the current challenges and potential solutions and provide future perspectives of human-virus PPI prediction in the coming post-AlphaFold2 era.

3.
Brief Bioinform ; 22(2): 832-844, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343659

ABSTRACT

While leading to millions of people's deaths every year the treatment of viral infectious diseases remains a huge public health challenge.Therefore, an in-depth understanding of human-virus protein-protein interactions (PPIs) as the molecular interface between a virus and its host cell is of paramount importance to obtain new insights into the pathogenesis of viral infections and development of antiviral therapeutic treatments. However, current human-virus PPI database resources are incomplete, lack annotation and usually do not provide the opportunity to computationally predict human-virus PPIs. Here, we present the Human-Virus Interaction DataBase (HVIDB, http://zzdlab.com/hvidb/) that provides comprehensively annotated human-virus PPI data as well as seamlessly integrates online PPI prediction tools. Currently, HVIDB highlights 48 643 experimentally verified human-virus PPIs covering 35 virus families, 6633 virally targeted host complexes, 3572 host dependency/restriction factors as well as 911 experimentally verified/predicted 3D complex structures of human-virus PPIs. Furthermore, our database resource provides tissue-specific expression profiles of 6790 human genes that are targeted by viruses and 129 Gene Expression Omnibus series of differentially expressed genes post-viral infections. Based on these multifaceted and annotated data, our database allows the users to easily obtain reliable information about PPIs of various human viruses and conduct an in-depth analysis of their inherent biological significance. In particular, HVIDB also integrates well-performing machine learning models to predict interactions between the human host and viral proteins that are based on (i) sequence embedding techniques, (ii) interolog mapping and (iii) domain-domain interaction inference. We anticipate that HVIDB will serve as a one-stop knowledge base to further guide hypothesis-driven experimental efforts to investigate human-virus relationships.


Subject(s)
Databases, Protein , Protein Interaction Mapping/methods , Proteins/metabolism , Viral Proteins/metabolism , Gene Expression Profiling , Humans , Machine Learning , Protein Array Analysis , Protein Conformation , Proteins/chemistry , Proteins/genetics , Viral Proteins/chemistry , Viral Proteins/genetics
4.
Bioinformatics ; 2021 Jul 17.
Article in English | MEDLINE | ID: covidwho-1316806

ABSTRACT

MOTIVATION: To complement experimental efforts, machine learning-based computational methods are playing an increasingly important role to predict human-virus protein-protein interactions (PPIs). Furthermore, transfer learning can effectively apply prior knowledge obtained from a large source dataset/task to a small target dataset/task, improving prediction performance. RESULTS: To predict interactions between human and viral proteins, we combine evolutionary sequence profile features with a Siamese convolutional neural network (CNN) architecture and a multi-layer perceptron. Our architecture outperforms various feature encodings-based machine learning and state-of-the-art prediction methods. As our main contribution, we introduce two transfer learning methods (i.e., 'frozen' type and 'fine-tuning' type) that reliably predict interactions in a target human-virus domain based on training in a source human-virus domain, by retraining CNN layers. Finally, we utilize the 'frozen' type transfer learning approach to predict human-SARS-CoV-2 PPIs, indicating that our predictions are topologically and functionally similar to experimentally known interactions. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

5.
Mol Cell ; 80(6): 1104-1122.e9, 2020 12 17.
Article in English | MEDLINE | ID: covidwho-933377

ABSTRACT

Human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative pathogen of the COVID-19 pandemic, exerts a massive health and socioeconomic crisis. The virus infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange, but the mechanisms driving infection and pathology are unclear. We performed a quantitative phosphoproteomic survey of induced pluripotent stem cell-derived AT2s (iAT2s) infected with SARS-CoV-2 at air-liquid interface (ALI). Time course analysis revealed rapid remodeling of diverse host systems, including signaling, RNA processing, translation, metabolism, nuclear integrity, protein trafficking, and cytoskeletal-microtubule organization, leading to cell cycle arrest, genotoxic stress, and innate immunity. Comparison to analogous data from transformed cell lines revealed respiratory-specific processes hijacked by SARS-CoV-2, highlighting potential novel therapeutic avenues that were validated by a high hit rate in a targeted small molecule screen in our iAT2 ALI system.


Subject(s)
Alveolar Epithelial Cells/metabolism , COVID-19/metabolism , Phosphoproteins/metabolism , Proteome/metabolism , SARS-CoV-2/metabolism , Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/virology , Animals , Antiviral Agents , COVID-19/drug therapy , COVID-19/genetics , COVID-19/pathology , Chlorocebus aethiops , Cytopathogenic Effect, Viral , Cytoskeleton , Drug Evaluation, Preclinical , Humans , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/pathology , Induced Pluripotent Stem Cells/virology , Phosphoproteins/genetics , Protein Transport , Proteome/genetics , SARS-CoV-2/genetics , Signal Transduction , Vero Cells
6.
Nature ; 582(7811): 230-233, 2020 06.
Article in English | MEDLINE | ID: covidwho-307789

ABSTRACT

Distrust in scientific expertise1-14 is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks2-4, as happened for measles in 20195,6. Homemade remedies7,8 and falsehoods are being shared widely on the Internet, as well as dismissals of expert advice9-11. There is a lack of understanding about how this distrust evolves at the system level13,14. Here we provide a map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users. Its core reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages. Although smaller in overall size, anti-vaccination clusters manage to become highly entangled with undecided clusters in the main online network, whereas pro-vaccination clusters are more peripheral. Our theoretical framework reproduces the recent explosive growth in anti-vaccination views, and predicts that these views will dominate in a decade. Insights provided by this framework can inform new policies and approaches to interrupt this shift to negative views. Our results challenge the conventional thinking about undecided individuals in issues of contention surrounding health, shed light on other issues of contention such as climate change11, and highlight the key role of network cluster dynamics in multi-species ecologies15.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Internationality , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Public Opinion , Social Media/statistics & numerical data , Vaccination/psychology , Algorithms , COVID-19 , COVID-19 Vaccines , Cluster Analysis , Coronavirus Infections/psychology , Humans , Time Factors , Viral Vaccines
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