Review

.2020 Jun;21(6):339-354.

doi: 10.1038/s41576-020-0212-5. Epub 2020 Feb 14.

A systems approach to infectious disease

Manon Eckhardt^#^{1 2 3}, Judd F Hultquist^#^{4 5 6 7}, Robyn M Kaake^{1 2 3}, Ruth Hüttenhain^{1 2 3}, Nevan J Krogan^{8 9 10}

Affiliations

¹ Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA.
² Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA, USA.
³ J. David Gladstone Institutes, San Francisco, CA, USA.
⁴ Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA. judd.hultquist@northwestern.edu.
⁵ Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA, USA. judd.hultquist@northwestern.edu.
⁶ J. David Gladstone Institutes, San Francisco, CA, USA. judd.hultquist@northwestern.edu.
⁷ Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. judd.hultquist@northwestern.edu.
⁸ Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA. nevan.krogan@ucsf.edu.
⁹ Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA, USA. nevan.krogan@ucsf.edu.
¹⁰ J. David Gladstone Institutes, San Francisco, CA, USA. nevan.krogan@ucsf.edu.

^# Contributed equally.

PMID:32060427
PMCID: PMC7839161
DOI: 10.1038/s41576-020-0212-5

Review

A systems approach to infectious disease

Manon Eckhardt et al. Nat Rev Genet.2020 Jun.

.2020 Jun;21(6):339-354.

doi: 10.1038/s41576-020-0212-5. Epub 2020 Feb 14.

Authors

Manon Eckhardt^#^{1 2 3}, Judd F Hultquist^#^{4 5 6 7}, Robyn M Kaake^{1 2 3}, Ruth Hüttenhain^{1 2 3}, Nevan J Krogan^{8 9 10}

Affiliations

¹ Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA.
² Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA, USA.
³ J. David Gladstone Institutes, San Francisco, CA, USA.
⁴ Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA. judd.hultquist@northwestern.edu.
⁵ Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA, USA. judd.hultquist@northwestern.edu.
⁶ J. David Gladstone Institutes, San Francisco, CA, USA. judd.hultquist@northwestern.edu.
⁷ Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. judd.hultquist@northwestern.edu.
⁸ Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA. nevan.krogan@ucsf.edu.
⁹ Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA, USA. nevan.krogan@ucsf.edu.
¹⁰ J. David Gladstone Institutes, San Francisco, CA, USA. nevan.krogan@ucsf.edu.

^# Contributed equally.

PMID:32060427
PMCID: PMC7839161
DOI: 10.1038/s41576-020-0212-5

Abstract

Ongoing social, political and ecological changes in the 21st century have placed more people at risk of life-threatening acute and chronic infections than ever before. The development of new diagnostic, prophylactic, therapeutic and curative strategies is critical to address this burden but is predicated on a detailed understanding of the immensely complex relationship between pathogens and their hosts. Traditional, reductionist approaches to investigate this dynamic often lack the scale and/or scope to faithfully model the dual and co-dependent nature of this relationship, limiting the success of translational efforts. With recent advances in large-scale, quantitative omics methods as well as in integrative analytical strategies, systems biology approaches for the study of infectious disease are quickly forming a new paradigm for how we understand and model host-pathogen relationships for translational applications. Here, we delineate a framework for a systems biology approach to infectious disease in three parts: discovery - the design, collection and analysis of omics data; representation - the iterative modelling, integration and visualization of complex data sets; and application - the interpretation and hypothesis-based inquiry towards translational outcomes.

PubMed Disclaimer

Conflict of interest statement

Competing interests

The authors declare no competing interests.

Figures

**Figure 1 |. Interdependence of host and pathogen.**
A representation of the intricate relationship between host and pathogen that ultimately dictates the outcome of infection on the spectrum between health and disease. Pathogens effect direct changes on the host, which in turn elicits a response to infection, both of which are influenced by the underlying environment. These influences dictate susceptibility versus resistance, tolerance versus pathogenicity, immune response versus immunodeficiency, virulence versus nonvirulence, and ultimately health versus disease. Systems biology approaches are especially valuable in infectious disease research as a way to capture a comprehensive picture of this intricate relationship.

**Figure 2 |. A systems biology framework.**
A visual representation of the steps we outline in this review as part of a systems biology approach to infectious disease from discovery to representation to application. Arrows highlight the iterative and interconnected nature of systems biology as a process. CRISPRa, CRISPR activation; CRISPRi, CRISPR inhibition; E-MAP; epistatic mini-array profile; GWAS, genome-wide association studies; RNAi, RNA interference; seq, sequencing.

**Figure 3 |. Systems biology technologies for infectious disease research.**
A summary of relevant omics technologies used in infectious disease research alongside the molecular signatures they are designed to capture.

**Figure 4 |. Assembly and representation of a network model.**
After the organization of the collected data into a tidy format (a), a simple network of nodes and edges can be assembled (b) with each node representing a component of the system and each edge representing their relationships. Varying the size, color, and organization of the nodes can be used to add dimension to the dataset by visualizing magnitude, p-value, or a common descriptor (c). Additional information can be depicted by varying edge characters such as width to indicate associative strength, gaps to indicate transience, or arrows to indicate directionality (d). Different types of data may benefit from different methods of depiction to complement the base network, including heatmaps to illustrate timecourse data or shading to illustrate pathway or complex membership (E).

See this image and copyright information in PMC

Cited by

Structure-function analysis of enterovirus protease 2A in complex with its essential host factor SETD3.
Peters CE, Schulze-Gahmen U, Eckhardt M, Jang GM, Xu J, Pulido EH, Bardine C, Craik CS, Ott M, Gozani O, Verba KA, Hüttenhain R, Carette JE, Krogan NJ.Peters CE, et al.Nat Commun. 2022 Sep 8;13(1):5282. doi: 10.1038/s41467-022-32758-3.Nat Commun. 2022.PMID:36075902Free PMC article.
Rationale and Criteria for a COVID-19 Model Framework.
Messina F, Montaldo C, Abbate I, Antonioli M, Bordoni V, Matusali G, Sacchi A, Giombini E, Fimia GM, Piacentini M, Capobianchi MR, Lauria FN, Ippolito G, On Behalf Of Covid-Scoping Review Working Group.Messina F, et al.Viruses. 2021 Jul 6;13(7):1309. doi: 10.3390/v13071309.Viruses. 2021.Retraction in:Viruses. 2021 Jul 29;13(8):1485. doi: 10.3390/v13081485.PMID:34372515Free PMC article.Retracted.
Respiratory Syncytial Virus Vaccine Design Using Structure-Based Machine-Learning Models.
McCarty TC, Vaisman II.McCarty TC, et al.Viruses. 2024 May 22;16(6):821. doi: 10.3390/v16060821.Viruses. 2024.PMID:38932114Free PMC article.
The microbiota as a modulator of mucosal inflammation and HIV/HPV pathogenesis: From association to causation.
Moreno E, Ron R, Serrano-Villar S.Moreno E, et al.Front Immunol. 2023 Jan 23;14:1072655. doi: 10.3389/fimmu.2023.1072655. eCollection 2023.Front Immunol. 2023.PMID:36756132Free PMC article.Review.
Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure.
Rando HM, MacLean AL, Lee AJ, Lordan R, Ray S, Bansal V, Skelly AN, Sell E, Dziak JJ, Shinholster L, D'Agostino McGowan L, Ben Guebila M, Wellhausen N, Knyazev S, Boca SM, Capone S, Qi Y, Park Y, Mai D, Sun Y, Boerckel JD, Brueffer C, Byrd JB, Kamil JP, Wang J, Velazquez R, Szeto GL, Barton JP, Goel RR, Mangul S, Lubiana T; COVID-19 Review Consortium Vikas Bansal, John P. Barton, Simina M. Boca, Joel D. Boerckel, Christian Brueffer, James Brian Byrd, Stephen Capone, Shikta Das, Anna Ada Dattoli, John J. Dziak, Jeffrey M. Field, Soumita Ghosh, Anthony Gitter, Rishi Raj Goel, Casey S. Greene, Marouen Ben Guebila, Daniel S. Himmelstein, Fengling Hu, Nafisa M. Jadavji, Jeremy P. Kamil, Sergey Knyazev, Likhitha Kolla, Alexandra J. Lee, Ronan Lordan, Tiago Lubiana, Temitayo Lukan, Adam L. MacLean, David Mai, Serghei Mangul, David Manheim, Lucy D’Agostino McGowan, Amruta Naik, YoSon Park, Dimitri Perrin, Yanjun Qi, Diane N. Rafizadeh, Bharath Ramsundar, Halie M. Rando, Sandipan Ray, Michael P. Robson, Vincent Rubinetti, Elizabeth Sell, Lamonica Shinholster, Ashwin N. Skelly, Yuchen Sun, Yusha Sun, Gregory L. Szeto, Ryan Velazquez, Jinhui Wang, Nils Wellhausen,; Gitter A, Greene CS.Rando HM, et al.mSystems. 2021 Oct 26;6(5):e0009521. doi: 10.1128/mSystems.00095-21. Epub 2021 Oct 26.mSystems. 2021.PMID:34698547Free PMC article.

See all "Cited by" articles

References

1. (WHO, W. H. O.) Global Health Estimates 2016: Disease burden by Cause, Age, Sex, by Country and by Region, 2000–2016. (2018).
1. Aderem A et al. A systems biology approach to infectious disease research: innovating the pathogen-host research paradigm. MBio 2, e00325–00310, doi:10.1128/mBio.00325-10 (2011). - DOI - PMC - PubMed
1. Hillmer RA Systems biology for biologists. PLoS Pathog 11, e1004786, doi:10.1371/journal.ppat.1004786 (2015). - DOI - PMC - PubMed
2. An approachable introduction to systems biology for experimentalists.
1. Kitano H Systems biology: a brief overview. Science 295, 1662–1664, doi:10.1126/science.1069492 (2002). - DOI - PubMed
2. A foundational introduction to the principles of systems biology.
1. Ideker T, Galitski T & Hood L A new approach to decoding life: systems biology. Annu Rev Genomics Hum Genet 2, 343–372, doi:10.1146/annurev.genom.2.1.343 (2001). - DOI - PubMed

Publication types

Actions
Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information

Movatterモバイル変換

Account

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Full text links

Actions

Share

A systems approach to infectious disease

Affiliations

A systems approach to infectious disease

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical