et al. A systems biology approach to infectious disease research: innovating the pathogen-host research paradigm. mBio
2, e00325-10 (2011). A perspective by leaders in the field of systems biology of infectious disease research.
Tisoncik, J. R. & Katze, M. G.
What is systems biology?
5, 139–141 (2010).
Katze, M. G. (ed.) Systems Biology (Springer, 2013).
Systems biology: evolving into the mainstream. Cell
144, 839–841 (2011).
Diercks, A. & Aderem, A.
Systems approaches to dissecting immunity. Curr. Top. Microbiol. Immunol.
363, 1–19 (2013).
Lauffenburger, D. A.
The multiple dimensions of integrative biology. Integr. Biol. (Camb.)
4, 9 (2012).
Multiscale analysis of biological systems. Acta Biotheor.
61, 3–19 (2013).
Geiss, G. K.
et al. Large-scale monitoring of host cell gene expression during HIV-1 infection using cDNA microarrays. Virology
266, 8–16 (2000).
Fukuyama, S. & Kawaoka, Y.
The pathogenesis of influenza virus infections: the contributions of virus and host factors. Curr. Opin. Immunol.
23, 481–486 (2011).
Korth, M. J., Tchitchek, N., Benecke, A. G. & Katze, M. G.
Systems approaches to influenza-virus host interactions and the pathogenesis of highly virulent and pandemic viruses. Semin. Immunol.
4 Dec 2012 (doi:10.1016/j.smim.2012.11.001).
Kash, J. C.
et al. Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus. Nature
443, 578–581 (2006).
et al. Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature
445, 319–323 (2007). The first study in which non-human primates are infected with the 1918 pandemic influenza virus. This study highlights the importance of the ability of the virus to modulate the host response.
Tisoncik, J. R.
et al. Into the eye of the cytokine storm. Microbiol. Molec Biol. Rev.
76, 16–32 (2012). A review discussing the cytokine storm in the context of viral infections, and how systems virology approaches have provided significant insights into the kinetics of cytokine gene expression.
Baskin, C. R.
et al. Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus. Proc. Natl Acad. Sci. USA
106, 3455–3460 (2009).
et al. Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes. PLoS Pathog.
5, e1000604 (2009).
et al. Lethal dissemination of H5N1 influenza virus is associated with dysregulation of inflammation and lipoxin signaling in a mouse model of infection. J. Virol.
84, 7613–7624 (2010).
Thomas, P. G.
et al. The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1. Immunity
30, 566–575 (2009).
Ichinohe, T., Lee, H. K., Ogura, Y., Flavell, R. & Iwasaki, A.
Inflammasome recognition of influenza virus is essential for adaptive immune responses. J. Exp. Med.
206, 79–87 (2009).
Allen, I. C.
et al. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity
30, 556–565 (2009).
Chang, S. T., Tchitchek, N., Ghosh, D., Benecke, A. & Katze, M. G.
A chemokine gene expression signature derived from meta-analysis predicts the pathogenicity of viral respiratory infections. BMC Syst. Biol.
5, 202 (2011).
Khondoker, M. R.
et al. Multi-factorial analysis of class predication error: estimating optimal number of biomarkers for various classification rules. J. Bioinform. Comput. Biol.
08, 945–965 (2010).
Pulendran, B., Li, S. & Nakaya, H. I.
Systems vaccinology. Immunity
33, 516–529 (2010).
Poland, G. A., Ovsyannikova, I. G., Kennedy, R. B., Haralambieva, I. H. & Jacobson, R. M.
Vaccinomics and a new paradigm for the development of preventive vaccines against viral infections. OMICS
15, 625–636 (2011). A review about a new paradigm for vaccine development. This is one of several reviews in a special issue of OMICS entitled Vaccines of the 21st Century: Vaccinomics for the Global Public Health.
Querec, T. D.
et al. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nature Immunol.
10, 116–125 (2009).
Nakaya, H. I.
et al. Systems biology of vaccination for seasonal influenza in humans. Nature Immunol.
12, 786–795 (2011).
et al. An integrated encyclopedia of DNA elements in the human genome. Nature
489, 57–74 (2012).
et al. Landscape of transcription in human cells. Nature
489, 101–108 (2012).
Skalsky, R. L.
et al. The viral and cellular microRNA targetome in lymphoblastoid cell lines. PLoS Pathog.
8, e1002484 (2012).
Mercer, T. R., Dinger, M. E. & Mattick, J. S.
Long non-coding RNAs: insights into functions. Nature Rev. Genet.
10, 155–159 (2009).
et al. Unique signatures of long noncoding RNA expression in response to virus infection and altered innate immune signaling. mBio
1, e00206-10 (2010). The first paper to report the discovery of differential expression of several long non-coding RNAs in response to SARS-CoV infection in four founder strains of the Collaborative Cross mouse model.
et al. Integrative deep sequencing of the mouse lung transcriptome reveals differential expression of diverse classes of small RNAs in response to respiratory virus infection. mBio
2, 00198-11 (2011).
Chang, S. T.
et al. Next-generation sequencing reveals HIV-1-mediated suppression of T cell activation and RNA processing and regulation of noncoding RNA expression in a CD4+ T cell line. mBio
2, e00134-11 (2011).
Chang, S. T.
et al. Next-generation sequencing of small RNAs from HIV-infected cells identifies phased microRNA expression patterns and candidate novel microRNAs differentially expressed upon infection. mBio
4, e00549-12 (2013).
et al. Decoding human cytomegalovirus. Science
338, 1088–1093 (2012).
Munger, J., Bajad, S. U., Coller, H. A., Shenk, T. & Rabinowitz, J. D.
Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS Pathog.
2, e132 (2006).
et al. Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy. Nature Biotech.
26, 1179–1186 (2008).
Vastag, L., Koyuncu, E., Grady, S. L., Shenk, T. E. & Rabinowitz, J. D.
Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism. PLoS Pathog.
7, e1002124 (2011).
McArdle, J., Schafer, X. L. & Munger, J.
Inhibition of calmodulin-dependent kinase kinase blocks human cytomegalovirus-induced glycolytic activation and severely attenuates production of viral progeny. J. Virol.
85, 705–714 (2011).
Spencer, C. M., Schafer, X. L., Moorman, N. J. & Munger, J.
Human cytomegalovirus induces the activity and expression of acetyl-coenzyme A carboxylase, a fatty acid biosynthetic enzyme whose inhibition attenuates viral replication. J. Virol.
85, 5814–5824 (2011).
Liu, S. T.
et al. Synaptic vesicle-like lipidome of human cytomegalovirus virions reveals a role for SNARE machinery in virion egress. Proc. Natl Acad. Sci. USA
108, 12869–12874 (2011).
McArdle, J., Moorman, N. J. & Munger, J.
HCMV targets the metabolic stress response through activation of AMPK whose activity is important for viral replication. PLoS Pathog.
8, e1002502 (2012).
Grady, S. L., Hwang, J., Vastag, L., Rabinowitz, J. D. & Shenk, T.
Herpes simplex virus 1 infection activates poly(ADP-ribose) polymerase and triggers the degradation of poly(ADP-ribose) glycohydrolase. J. Virol.
86, 8259–8268 (2012).
et al. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. PLoS Biol.
9, e1000598 (2011).
et al. The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors. PLoS Pathog.
7, e1002331 (2011).
Brass, A. L.
et al. Identification of host proteins required for HIV infection through a functional genomic screen. Science
319, 921–926 (2008).
Krishnan, M. N.
et al. RNA interference screen for human genes associated with West Nile virus infection. Nature
455, 242–245 (2008).
Sessions, O. M.
et al. Discovery of insect and human dengue virus host factors. Nature
458, 1047–1050 (2009).
Brass, A. L.
et al. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell
139, 1243–1254 (2009).
et al. A genome-wide genetic screen for host factors required for hepatitis C virus propagation. Proc. Natl Acad. Sci. USA
106, 16410–16415 (2009).
The Complex Trait Consortium. The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nature Genet.
36, 1133–1137 (2004).
et al. Herpesviral protein networks and their interaction with the human proteome. Science
311, 239–242 (2006).
Friedel, C. C. & Haas, J.
Virus–host interactomes and global models of virus-infected cells. Trends Microbiol.
19, 501–508 (2011).
Ma-Lauer, Y., Lei, J., Hilgenfeld, R. & von Brunn, A.
Virus–host interactomes — antiviral drug discovery. Curr. Opin. Virol.
2, 614–621 (2012).
Panda, D. & Cherry, S.
Cell-based genomic screening: elucidating virus–host interactions. Curr. Opin. Virol.
2, 778–786 (2012).
Stertz, S. & Shaw, M. L.
Uncovering the global host cell requirements for influenza virus replication via RNAi screening. Microbes Infect.
13, 516–525 (2011).
Meyniel-Schicklin, L., de Chassey, B., Andre, P. & Lotteau, V.
Viruses and interactomes in translation. Mol. Cell. Proteomics
11, M111.014738 (2012).
et al. Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature
487, 491–495 (2012). A study that identifies potential cancer-causing driver genes by combining data from tumour virus–host interactomes with data about changes in the host transcriptome on expression of tumour virus ORFs.
et al. Expression quantitative trait loci for extreme host response to influenza A in pre-collaborative cross mice. G3 (Bethesda)
2, 213–221 (2012).
Laird, P. W.
Principles and challenges of genomewide DNA methylation analysis. Nature Rev. Genet.
11, 191–203 (2010).
Garcia, B. A.
Mass spectrometric analysis of histone variants and post-translational modifications. Front. Biosci. (Schol. Ed.)
1, 142–153 (2009).
Knight, J. C.
Genomic modulators of the immune response. Trends Genet.
29, 74–83 (2012).
Ernberg, I., Karimi, M. & Ekstrom, T. J.
Epigenetic mechanisms as targets and companions of viral assaults. Ann. NY Acad. Sci.
1230, E29–E36 (2011).
et al. Suppression of the antiviral response by an influenza histone mimic. Nature
483, 428–433 (2012).
Gene regulatory network inference using out of equilibrium statistical mechanics. HFSP J.
2, 183–188 (2008).
Out-of-equilibrium dynamics of gene expression and the Jarzynski equality. Phys. Rev. Lett.
100, 188101 (2008).
McDermott, J. E., Taylor, R. C., Yoon, H. & Heffron, F.
Bottlenecks and hubs in inferred networks are important for virulence in Salmonella typhimurium. J. Comput. Biol.
16, 169–180 (2009).
Girvan, M. & Newman, M. E. J.
Community structure in social and biological networks. Proc. Natl Acad. Sci. USA
99, 7821–7826 (2002).
et al. Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data. Nature Genet.
34, 166–176 (2003).
Shapira, S. D.
et al. A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection. Cell
139, 1255–1267 (2009).
Diamond, D. L.
et al. Temporal proteome and lipidome profiles reveal hepatitis C virus-associated reprogramming of hepatocellular metabolism and bioenergetics. PLoS Pathog.
6, e1000719 (2010).
McDermott, J. E.
et al. Topological analysis of protein co-abundance networks identifies novel host targets important for HCV infection and pathogenesis. BMC Syst. Biol.
6, 28 (2012).
Rasmussen, A. L.
et al. Systems virology identifies a mitochondrial fatty acid oxidation enzyme, dodecenoyl coenzyme A delta isomerase, required for hepatitis C virus replication and likely pathogenesis. J. Virol.
85, 11646–11654 (2011).
Tripathi, L. P.
et al. Network based analysis of hepatitis C virus core and NS4B protein interactions. Mol. Biosyst.
6, 2539–2553 (2010).
et al. Increased viral loads and exacerbated innate host response in aged macaques infected with 2009 pandemic H1N1 influenza A virus. J. Virol.
86, 11115–11127 (2012).
Lau, K. S.
et al. In vivo systems analysis identifies spatial and temporal aspects of the modulation of TNF-α-induced apoptosis and proliferation by MAPKs. Sci. Signal.
4, ra16 (2011).
Lau, K. S.
et al. Multi-scale in vivo systems analysis reveals the influence of immune cells on TNF-α-induced apoptosis in the intestinal epithelium. PLoS Biol.
10, e1001393 (2012).
Benecke, A., Gale, M. Jr & Katze, M. G.
Dynamics of innate immunity are key to chronic immune activation in AIDS. Curr. Opin. HIV AIDS
7, 79–85 (2012).
Benecke, A. G.
Critical dynamics in host–pathogen systems. Curr. Top. Microbiol. Immunol.
363, 235–259 (2013).
Graphic requirements for multistationarity. ComPlexUs
1, 123–133 (2003).
Cinquin, O. & Demongeot, J.
High-dimensional switches and the modelling of cellular differentiation. J. Theor. Biol.
233, 391–411 (2005).
Becavin, C., Tchitchek, N., Mintsa-Eya, C., Lesne, A. & Benecke, A.
Improving the efficiency of multidimensional scaling in the analysis of high-dimensional data using singular value decomposition. Bioinformatics
27, 1413–1421 (2011).
Becavin, C. & Benecke, A.
New dimensionality reduction methods for the representation of high dimensional 'omics' data. Expert Rev. Mol. Diagnost.
11, 27–34 (2011). A review that discusses the need for the development of dimensionality reduction and visualization methods, and presents an example of how existing techniques can be combined to overcome the current limitations. This review also discusses future directions in the field.
Rasmussen, A. L.
et al. Early transcriptional programming links progression to hepatitis C virus-induced severe liver disease in transplant patients. Hepatology
56, 17–27 (2012).
Diamond, D. L.
et al. Proteome and computational analyses reveal new insights into the mechanisms of hepatitis C virus-mediated liver disease posttransplantation. Hepatology
56, 28–38 (2012).
et al. A network perspective on metabolic inconsistency. BMC Syst. Biol.
6, 41 (2012).
Ponnapalli, S. P., Saunders, M. A., Van Loan, C. F. & Alter, O.
A higher-order generalized singular value decomposition for comparison of global mRNA expression from multiple organisms. PLoS ONE
6, e28072 (2011).
Huang, S. S. & Fraenkel, E.
Integrating proteomic, transcriptional, and interactome data reveals hidden components of signaling and regulatory networks. Sci. Signal.
2, ra40 (2009). The description of a computational method (based on the Steiner tree problem) that provides a general framework for building models of regulatory networks from high-throughput data sets.
Luksza, M., Lassig, M. & Berg, J.
Significance analysis and statistical mechanics: an application to clustering. Phys. Rev. Lett.
105, 220601 (2010).
et al. Gene expression signature-based screening identifies new broadly effective influenza A antivirals. PLoS ONE
5, e13169 (2010).
Yang, W.-L. R., Lee, Y.-E., Chen, M.-H., Chao, K.-M. & Huang, C.-Y. F.
In-silico drug screening and potential target identification for hepatocellular carcinoma using Support Vector Machines based on drug screening result. Gene
518, 201–208 (2013).
Hood, L. & Friend, S. H.
Predictive, personalized, preventive, participatory (P4) cancer medicine. Nature Rev. Clin. Oncol.
8, 184–187 (2011).
Bengoechea, J. A.
Infection systems biology: from reactive to proactive (P4) medicine. Int. Microbiol.
15, 55–60 (2012).
Southern, E. M.
DNA microarrays. History and overview. Methods Mol. Biol.
170, 1–15 (2001).
Gorreta, F., Carbone, W. & Barzaghi, D. in Molecular Profiling (eds Espina, V. & Liotta, L. A.) 89–105 (Humana, 2012).
Li, W. & Ruan, K.
MicroRNA detection by microarray. Anal. Bioanal. Chem.
394, 1117–1124 (2009).
Fouse, S. D., Nagarajan, R. P. & Costello, J. F.
Genome-scale DNA methylation analysis. Epigenomics
2, 105–117 (2010).
Lam, C.-W., Lau, K.-C. & Tong, S.-F.
Microarrays for personalized genomic medicine. Adv. Clin. Chem.
52, 1–18 (2010).
Metzker, M. L.
Sequencing technologies — the next generation. Nature Rev. Genet.
11, 31–46 (2010).
Wang, Z., Gerstein, M. & Snyder, M.
RNA-Seq: a revolutionary tool for transcriptomics. Nature Rev. Genet.
10, 57–63 (2009).
Martin, J. A. & Wang, Z.
Next-generation transcriptome assembly. Nature Rev. Genet.
12, 671–682 (2011).
Park, P. J.
ChIP-seq: advantages and challenges of a maturing technology. Nature Rev. Genet.
10, 669–680 (2009).
König, J., Zarnack, K., Luscombe, N. M. & Ule, J.
Protein–RNA interactions: new genomic technologies and perspectives. Nature Rev. Genet.
13, 77–83 (2012).
Collaborative-Cross-Consortium. The genome architecture of the Collaborative Cross mouse genetic reference population. Genetics
190, 389–401 (2012).
et al. Quantitative trait locus analysis using recombinant inbred intercrosses: theoretical and empirical considerations. Genetics
170, 1299–1311 (2005).