Global Collaboration Research Strategies for Sustainability in the Post COVID-19 Era: Analyzing Virology-Related National-Funded Projects

: In the post-COVID-19 era, virology-related research, which not only depends on the governments as its main source of funding but also requires international and interdisciplinary collaborations, is recognized as an essential defense for sustainability. Few published studies have examined the trend, but only for certain viruses before the mid-2010s. Moreover, it is challenging to deﬁne generally accepted virology-related research ﬁelds due to its broad spectrum. Thus, it is time that we confront the unprecedented pandemic to understand the status of nationally supported projects in developed nations to establish international collaborative research strategies from an interdisciplinary perspective. In this study, 32,365 national-funded projects were collected from the US, EU, and Japan and assigned to ﬁve scientiﬁc ﬁelds to conduct a cluster analysis. Then, an expert-based approach was utilized to deﬁne an individual cluster. Moreover, a comparative analysis between nations was carried out to determine if there was a competitive edge for collaboration. As a result, a framework for virology-related research areas was constructed to provide the status quo and di ﬀ erences between nations’ research capabilities, thereby eliciting practical global research and development (R&D) cooperation to achieve a common agenda and a direction for goals in the post-COVID-19 era. These ﬁndings have implications for viral response R&D, policy, and practice for future pandemics. A systematic approach based on scientiﬁc evidence and an R&D collaboration strategy between industry and academia is essential to resolve the interdisciplinary barriers between countries and promote sustainable virus R&D collaboration.


Introduction
The world is confronting a significant pandemic caused by SARS-CoV-2, the coronavirus causing COVID-19. Although historically, humans have survived various pandemics stemming from infectious diseases, the current pandemic's rapid global transmission rate is unprecedented due to modern globalization. According to Johns Hopkins University [1], the pandemic has affected 188 countries and territories, with around 11,449,707 global cases of infections and more than 534,267 deaths. Many nations have started to avoid the threat of a second wave of infections by requiring or advising the use of facial masks and by practicing social distancing. The global economy could be impacted by a devastating $82.4 trillion (16.3 percent) economic loss related to the COVID-19 pandemic over the next five years in the event of an economic depression [2]. Namely, the global health crisis caused by the pandemic significantly slows the progress of sustainability.
Many nations have dramatically increased their government investments in science in the hope of taming the crisis. The United States has played a critical role in advancing science and has severely 1.
What virus-related interdisciplinary research has been conducted amongst developed countries since 2015?

2.
What is the nationality of the organizations as partners for global collaboration in virus-related R&D fields? 3.
What differences exist amongst viruses-related R&D fields?
This paper consists of four sections. Following this general introduction, the "materials and methods" section describes the framework and methodology. The "results" section presents comparative results of the research profiling and machine learning analyses. The "conclusion and discussion" section reviews our research, identifies research limitations, and indicates promising research opportunities to pursue in the future.

Data Collection and Preprocessing
Many studies have indicated that the US, EU, and Japan have critical roles in the scientific and technological advancements in terms of R&D spending [25]. The data used in this study was collected from the global R&D database and was established on the basis of national research funding data stemmed from STAR METRICS of the US, CORDIS (Community Research and Development Information Service) of the EU, and KAKEN (Database of Grants-in-Aid for Scientific Research) of Japan. The global R&D database has been built and operated by the Korea Institute of Science and Technology Information (KISTI), funded internally by the Ministry of Science and ICT of Korea. It has data from approximately 1 million nationally funded projects between 2012-2018. The detailed process of database establishment was described by Heo et al. [24].
To collect virology-related research funding data that started between 2014 and 2018, a machine learning process, called the ASJC code (All Science Journal Classification Codes), was conducted to assign individual funding data into five scientific fields out of 344 scientific fields that were classified by Scopus [24] based on the similarity between their title and abstract and their funding data. In this study we used the funding data that were located in Virology (2406), Microbiology (2404), Immunology (2403), Applied Microbiology and Biotechnology (2402), Immunology and Microbiology (all) (2400), Immunology and Microbiology (miscellaneous) (2401), Epidemiology (2713), Infectious diseases (2725), and Microbiology (medical) (2726) fields. After removing duplicated data, organization, and funding of missing data, workshop/conference/seminar/symposium/congress-related data, etc., the final set of data used is displayed in Table 1.

Co-Occurrence Matrix
As a way to identify virology-related R&D areas from an interdisciplinary perspective, a co-occurrence technique was used in terms of disciplines represented by the 344 ASJC codes by using the Vantage Point ® system (Search Tech, Inc., Herndon, VA, USA, Version 12) as previously demonstrated [24]. The tool has been widely used to map the scientific landscape of medical research [26][27][28] and allows the co-occurrence matrix to be built showing the records in the dataset contained in two given lists as follows: • The co-occurrence matrix: it shows the number of records in which the element i (from the first list) and the element j (from the second list) appear together where i,j = All Science Journal Classification Codes Namely, the more often a group of ASJC codes appears, the higher the relevance of the projects that have these ASJC codes. For example, a group of projects that contain disciplines such as Virology (2406), Microbiology (2404), Immunology (2403) is more relevant than that of projects that have those such as Epidemiology (2713), Infectious diseases (2725), and Microbiology (medical) (2726).

Clustering, Network Visualization, Defining Virology-Related R&D Areas
The network was built based on placing the degree of ASJC codes of projects into the co-occurrence matrix of projects. All nodes in the network were displayed under the field titles of ASJC codes, and the font size is related to the frequency of co-occurrence of each ASJC code. By visualizing this network structure, we can figure out the relationship between ASJC codes. The VOSViewer (Version 1.6.15, Leiden University, Leiden, The Netherlands) software was used as a network structure visualization tool and is widely used in bibliometric analyses, especially in cluster analyses [29]. The first step for constructing a map is to calculate the similarity matrix as input. The similarity matrix can be obtained from a co-occurrence matrix. The second step is to layout ASJC codes on the map based on the similarity matrix. ASJC codes that have a high similarity should be located close to each other, while ASJC codes that have a low similarity should be located far from each other. The VOS mapping technique is to minimize a weighted sum of the squared Euclidean distance between all pairs of ASJC codes. The higher the similarity between the two ASJC codes, the higher the weight of their squared distance in the summation. The constraint is imposed that the average distance between two ASJC codes must be equal to one in order to avoid trivial maps in which all ASJC codes have the same location. To solve the problem, VOSviewer employed that minimization of the objective functions is performed subject to the constraint. The constrained optimization problem is first converted into an unconstrained optimization problem. The latter problem is then solved using a majorization algorithm [30]. The resulting visualizations show the clustering of relevant multiple disciplines representing major research areas. The constructed clusters were initially conducted, and then more sub-clusters were derived from larger clusters through using the two types of software, as mentioned above. The definition of virology-related R&D areas can only be seen by looking directly at the R&D projects that were composed of actual clusters or sub-clusters through virology-related experts who can provide relevant knowledge and expertise for investigating particular research fields. Therefore, we first ascertained the approximate R&D area by grasping the component ASJC codes constituting each sub-cluster. After that, the contents of the titles and abstracts of the projects in the sub-clusters were checked, and the research fields of each sub-cluster were defined. In order to compare countries, the estimated total amount of funding for the US, EU and Japan's projects in each (sub-) cluster were calculated individually, and a comparative ratio analysis was conducted to derive implications of the commonalities and differences between the US, EU, and Japan in virology-related research areas from an interdisciplinary perspective. The entire process is depicted in Figure 1.

Results
The network visualization of virology-related research fields is shown in Figure 2. In this study, an item (sometimes called a node) that is treated as the object of interest, is a discipline that is measured by an ASJC code. A link (sometimes called an edge), which implies a relationship between two items, is a co-occurrence link between disciplines (ASJC codes). The strength (sometimes called weight) of a link may, in this study, indicate the number of projects in which two disciplines (ASJC codes) occur together. The size of the label and the circles of a discipline (an ASJC code) is determined by the weight of the discipline. The higher the weight of a discipline (an ASJC code), the larger the label and the circles of a discipline (an ASJC code). The color of a discipline (an ASJC code) is determined by the cluster to which the discipline (the ASJC code) belongs. The broad spectrum of virology-related projects in cluster 1 can be considered part of the "One Health" perspective, which recognizes the interconnection/interactions between people, animals, plants, and their shared environment [31], and are conducted chiefly based on Infectious Diseases (2725), Virology (2406), and Clinical Biochemistry (1308). Research based on the viruses that exist on the Earth from a global ecosystem's viewpoint is grouped under the sub-cluster 1-1. Research on vaccines for livestock, plant, and humans is grouped in the sub-cluster 1-2. There are two topics in the sub-cluster 1-3. One is associated with the efficient production of agriculture, fishery, and livestock under climate change and global warming. The other is related to research on viral infections that caused harmful productions. Thus, we labeled cluster 1-1, cluster 1-2, and cluster 1-3 as, "The research on identification, separation, and characterization of pathogens in the global ecosystem (sub-cluster 1-1)", "The discovery of biomarkers for detection and diagnosis of viruses, target molecules and treatment targets, development of vaccines, and anti-viral agents (sub-cluster 1-2)", and "Research on detection and diagnosis technology for virus infections of agricultural and horticultural products triggered by climate change, virus control technology, and virus infection path and interaction mechanism (sub-cluster 1-3)", respectively. Two topics in the sub-cluster 1-3 were named, "The research on improving the production efficiency and profitability of agriculture, fishery, and livestock industries due to climate change and global warming (sub-cluster 1-3-1)" and "The research

Results
The network visualization of virology-related research fields is shown in Figure 2. In this study, an item (sometimes called a node) that is treated as the object of interest, is a discipline that is measured by an ASJC code. A link (sometimes called an edge), which implies a relationship between two items, is a co-occurrence link between disciplines (ASJC codes). The strength (sometimes called weight) of a link may, in this study, indicate the number of projects in which two disciplines (ASJC codes) occur together. The size of the label and the circles of a discipline (an ASJC code) is determined by the weight of the discipline. The higher the weight of a discipline (an ASJC code), the larger the label and the circles of a discipline (an ASJC code). The color of a discipline (an ASJC code) is determined by the cluster to which the discipline (the ASJC code) belongs. The broad spectrum of virology-related projects in cluster 1 can be considered part of the "One Health" perspective, which recognizes the interconnection/interactions between people, animals, plants, and their shared environment [31], and are conducted chiefly based on Infectious Diseases (2725), Virology (2406), and Clinical Biochemistry (1308). Research based on the viruses that exist on the Earth from a global ecosystem's viewpoint is grouped under the sub-cluster 1-1. Research on vaccines for livestock, plant, and humans is grouped in the sub-cluster 1-2. There are two topics in the sub-cluster 1-3. One is associated with the efficient production of agriculture, fishery, and livestock under climate change and global warming. The other is related to research on viral infections that caused harmful productions. Thus, we labeled cluster 1-1, cluster 1-2, and cluster 1-3 as, "The research on identification, separation, and characterization of pathogens in the global ecosystem (sub-cluster 1-1)", "The discovery of biomarkers for detection and diagnosis of viruses, target molecules and treatment targets, development of vaccines, and anti-viral agents (sub-cluster 1-2)", and "Research on detection and diagnosis technology for virus infections of agricultural and horticultural products triggered by climate change, virus control technology, and virus infection path and interaction mechanism (sub-cluster 1-3)", respectively. Two topics in the sub-cluster 1-3 were named, "The research on improving the production efficiency and profitability of agriculture, fishery, and livestock industries due to climate change and global warming (sub-cluster 1-3-1)" and "The research on the identification of the interaction between host and pathogen in disease caused by viral infections and the route of infection (sub-cluster 1-3-2)", respectively.  The research on identification, separation, and characterization of pathogens in the global ecosystem (sub-cluster 1-1) is composed of 91 projects worth a total of $73,783,379.

Research Areas on Virology-Related National-Funded Projects of the US, EU, and Japan
The nationally represented funded projects are shown in Table 2  The research on the immunosuppression for viral infected patients and that on traditional virology such as HIV, HSV, and HPV was linked to the cluster 2-1 and 2-1, respectively. Moreover, nationally funded projects in cluster 2 were generally carried out in terms of Molecular Medicine (1313), Immunology (2403), Biochemistry, Genetics and Molecular biology (1301). Thus, sub-cluster 2-1 was named, "The research on mechanisms of immune response by viral infection, complications by viral infection during immunotherapy in acute or chronic immune disease, and modulation of immune response mechanism." Sub-cluster 2-2 was titled "Antiviral agent design, treatment, and immune-enhancing molecular mechanisms in chronic viral infections." In the cluster 3, there were some research topics that were related to the prevention of infectious diseases in the home care and management of patients, and patient care environment, hygiene, public health policy, management, and education and that was closely associated with Epidemiology (2713), Health Policy (2719), Public Health, Environmental and Occupational Health (2739), thereby incurring the name, "Social studies on the prevention of infectious diseases in healthcare system." In the next subsection, detailed investigations for each cluster will be described. The research on identification, separation, and characterization of pathogens in the global ecosystem (sub-cluster 1-1) is composed of 91 projects worth a total of $73,783,379.
The nationally represented funded projects are shown in Table 2.  The discovering biomarkers for detection and diagnosis of viruses, target molecules and treatment targets, development of vaccines, anti-viral agents (sub-cluster 1-2) comprised of 67 projects worth $35,596,415. The representative nationally funded projects are indicated in Table 3. In the US, the CrossLife Technologies Inc. and Instadiagnostics Inc. committed to spending $224,929 yearly on their study of SBIR Phase I Rapid instrument free Nucleic Acid Test for Pathogens and Biothreats  Research on detection and diagnosis technology for virus infections of agricultural and horticultural products triggered by climate change, virus control technology, and virus infection path and interaction mechanism (sub-cluster 1-3) is composed of 107 projects worth $306,727,248 and may be divided into two topics: (1) research on improving the production efficiency and profitability of agriculture, fishery, and livestock industries due to climate change and global warming (sub-cluster 1-3-1); and (2) the research on the identification of interaction between host and pathogen in diseases caused by viral infections and the route of infection (sub-cluster 1-3-2).
The nationally represented funded projects of sub-cluster 1-3-1 are indicated in Table 4  The nationally funded projects represented in sub-cluster 1-3-2 are shown in Table 5

Social Studies for the Prevention of Infectious Diseases in Healthcare Systems (cluster 3).
The social studies for the prevention of infectious diseases in healthcare systems (cluster 3) had 134 projects totaling $210,907,552. The nationally represented funded projects are indicated in Table 8.

Comparison Among the US, EU, and Japan
The estimated total R&D project funding of virology-related research fields and the frequency of disciplines (ASJC codes) of (sub-) clusters of virology-related research areas among the US, EU, and Japan are shown in Figures 3 and 4, respectively.
The US and EU share the same interest in cluster 2. However, the US has heavily invested in research in cluster 2-2 (35.5%), which is specifically related to cancers and chronic viral diseases such as (HIV, HSV, HPV, HBV, HCV, etc.). When taking a closer look at the characteristics of disciplines (see Figure 4), the major disciplines of cluster 2-1 and cluster 2-2 are Immunology (2403), Cell Biology (1307), Immunology and Allergy (2723) and Cancer Research (1306), Biochemistry, Genetics and Molecular Biology (1301), and Molecular Medicine (1313), respectively. The EU has also shown a concentrated investment pattern in cluster 2, but unlike the United States, it invested mostly in cluster 2-1 (29.8%), or research areas for immune response regulations and control mechanisms as a policy for investment in research and development in response to viruses. In addition, the EU's ratio of research areas for (sub-) cluster 1 and cluster 3 are evenly distributed compared to that of the US, which reflects the characteristics of balanced R&D funding. After taking these results into consideration, it is obvious that the US is unrivaled in the research area of immune responses to viral infections, control of immune responses and complications stemming from infections during immunologic inhibition therapy for chronic virus diseases; and antiviral preparation design, treatment, and immune-enhancing molecular mechanisms in chronic viral infections.
Meanwhile, the ratio of research areas of (sub-) cluster 1 and cluster 3 of the EU are evenly distributed compared to that of the US, which reflects the characteristics of balanced R&D funding that oriented on a common agenda as a nation. Although the funding patterns of research areas of Japan are likely to follow those of the US, there are two main differences compared to the US. The first one is that various projects in the cluster 1-3 of the US and EU were carried out on the basis of Agronomy and Crop Science (1102) and Agricultural and Biological Sciences (1101). Japan primarily investigated different disciplines such as Animal Science and Zoology (ASJC: 1103), Horticulture (ASJC: 1108), Food Science (ASJC: 1106). The other main difference is that many Japanese government-supported projects in cluster 1-2 were mostly fulfilled in terms of Bioengineering (1502), Biotechnology (1305), Applied Microbiology and Biotechnology (2402), Biophysics (1304) rather than focusing on Clinical Biochemistry (1308) and Biomedical Engineering (2204) like those of the US.

Discussions and Conclusions
It cannot be emphasized enough, that a better understanding of virology-related research is the fundamental weapon that protects us from future pandemics. From the viewpoint of virology-related experts who decide what to investigate, definitions of virology-related research areas may be varied, which may cause a disagreement as to what is the consensus on generally accepted R&D investment fields. Thus, the purpose of this study was to clarify virology-related research areas by analyzing nationally funded projects in leading nations since 2012, thereby providing evidence-based information to guide strategic global collaboration in time for the next pandemic.
The present study presents two important outcomes. The first one is that we demonstrated how to operationalize the procedure for identifying research areas where nations may be invested based on virology-related national funding data. Virology-related research is acknowledged as playing a fundamental role in protecting humanity from many critical infectious diseases. However, there is no consensus on generally accepted virology-related research fields, so researchers and decisionmakers are confused when trying to establish strategies and policies. The result of the analysis explicitly verifies seven government-funded key research topics in the virology-related domains, indicates the core organizations in the main research areas for each nation, and induces the necessity for global collaboration based on the comparative analysis of nations. The procedure has the potential to be applied to any national science policies that are based on nationally funded projects. It is in line with the current trend of funding data-based research policies emphasized by prestigious scholars in

Discussions and Conclusions
It cannot be emphasized enough, that a better understanding of virology-related research is the fundamental weapon that protects us from future pandemics. From the viewpoint of virology-related experts who decide what to investigate, definitions of virology-related research areas may be varied, which may cause a disagreement as to what is the consensus on generally accepted R&D investment fields. Thus, the purpose of this study was to clarify virology-related research areas by analyzing nationally funded projects in leading nations since 2012, thereby providing evidence-based information to guide strategic global collaboration in time for the next pandemic.
The present study presents two important outcomes. The first one is that we demonstrated how to operationalize the procedure for identifying research areas where nations may be invested based on virology-related national funding data. Virology-related research is acknowledged as playing a fundamental role in protecting humanity from many critical infectious diseases. However, there is no consensus on generally accepted virology-related research fields, so researchers and decision-makers are confused when trying to establish strategies and policies. The result of the analysis explicitly verifies seven government-funded key research topics in the virology-related domains, indicates the core organizations in the main research areas for each nation, and induces the necessity for global collaboration based on the comparative analysis of nations. The procedure has the potential to be applied to any national science policies that are based on nationally funded projects. It is in line with the current trend of funding data-based research policies emphasized by prestigious scholars in science policy [19] and lays the groundwork for national science policies toward the global collaboration project. It can eventually improve the authority and legitimacy between stakeholders, including research experts, scientific advisors, and policymakers, who particularly work on controversial topics such as climate change, pandemics, and cyber-security, during the policy establishment process, thereby increasing their commitment to the policy implementation [22].
The other important outcome from this study is that this research enables research directors and/or policy decision-makers to debate the status quo of virology-related research areas at various levels. Thus, the results allow them to consider the framework for examining particular R&D issues on a micro level. For instance, an organization and/or a nation that is interested in vaccines for viral diseases may deliberate an R&D strategy using the information clusters. Moreover, they provide useful information in order to discuss the overarching goals of achieving a global defense strategy for the next pandemic on the basis of the comparative analysis. Our results indicate that the US has built national competitiveness in cluster 2. In contrast, the EU and Japan have relatively competitive edges in the social studies domains for the prevention of infectious diseases in healthcare systems (cluster 3) and discovering biomarkers for the detection and diagnosis of viruses, targeting molecules and treatment targets, the development of vaccines and anti-viral agents (sub-cluster 1-2), respectively. In a situation requiring exorbitant amounts of funding for taming the current coronavirus crisis and defending (re-) emerging potential lethal viruses, there is a need to establish a collaborative research policy that may accomplish the desired purpose of securing global human health and well-being; this may be accelerated by this study. As a consequence, this study may not only harmonize the operational and financial strategies in support of leading countries, increasing their efficiency and reducing the burden on countries, but it may also strengthen the collaboration among nations for better health to promote sustainability.
The limitations of this study present some challenging questions for future research. One inherent limitation concerns the US dataset that ranked the top shares of worldwide R&D expenditures rather than by country. Therefore, it causes a "home advantage" effect that underestimates the R&D activities of organizations operating outside of the home country due to the massive-scale funding data of the US, as Criscuolo [32] pointed out. It is desirable to collect more funding data from individual members of the EU, China, and South Korea in order to conduct a better comparative analysis among nations. The other limitation is that various cluster tools such as NetMiner, CiteSpace, and HistCite exist in the bibliometric research field. Each tool was developed by different, but similar algorithms so that it provides different clusters of closely associated items. Thus, it would be useful to examine a comparative study of the aforementioned tools.

Conflicts of Interest:
The authors declare no conflict of interest.