An Integrated, High-Throughput Strategy for Multiomic Systems Level Analysis.

Proteomics, metabolomics, and transcriptomics generate comprehensive data sets, and current biocomputational capabilities allow their efficient integration for systems biology analysis. Published multiomics studies cover methodological advances as well as applications to biological questions. However, few studies have focused on the development of a high-throughput, unified sample preparation approach to complement high-throughput omic analytics. This report details the automation, benchmarking, and application of a strategy for transcriptomic, proteomic, and metabolomic analyses from a common sample. The approach, sample preparation for multi-omics technologies (SPOT), provides equivalent performance to typical individual omic preparation methods but greatly enhances throughput and minimizes the resources required for multiomic experiments. SPOT was applied to a multiomics time course experiment for zinc-treated HL-60 cells. The data reveal Zn effects on NRF2 antioxidant and NFkappaB signaling. High-throughput approaches such as these are critical for the acquisition of temporally resolved, multicondition, large multiomic data sets such as those necessary to assess complex clinical and biological concerns. Ultimately, this type of approach will provide an expanded understanding of challenging scientific questions across many fields.

[1]  A. Butte,et al.  The Integrative Human Microbiome Project: Dynamic Analysis of Microbiome-Host Omics Profiles during Periods of Human Health and Disease , 2014, Cell host & microbe.

[2]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[3]  Joshua S Yuan,et al.  Plant systems biology comes of age. , 2008, Trends in plant science.

[4]  W. Wahli,et al.  PPARs at the crossroads of lipid signaling and inflammation , 2012, Trends in Endocrinology & Metabolism.

[5]  O. Elroy-Stein,et al.  Uncovering Hidden Layers of Cell Cycle Regulation through Integrative Multi-omic Analysis , 2015, PLoS genetics.

[6]  J. Asara,et al.  Triomics Analysis of Imatinib-Treated Myeloma Cells Connects Kinase Inhibition to RNA Processing and Decreased Lipid Biosynthesis. , 2015, Analytical chemistry.

[7]  A. Caudy,et al.  Targeted metabolomics in cultured cells and tissues by mass spectrometry: method development and validation. , 2014, Analytica chimica acta.

[8]  R. Goodacre,et al.  Metabolite extraction from suspension-cultured mammalian cells for global metabolite profiling , 2011, Nature Protocols.

[9]  M. Karin,et al.  p62/SQSTM1—Dr. Jekyll and Mr. Hyde that prevents oxidative stress but promotes liver cancer , 2016, FEBS letters.

[10]  Y. Li,et al.  Control of life-or-death decisions by RIP1 kinase. , 2014, Annual review of physiology.

[11]  P. May,et al.  Condensing the omics fog of microbial communities. , 2013, Trends in microbiology.

[12]  M E J Newman,et al.  Modularity and community structure in networks. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Paige Lacy.  Mechanisms of Degranulation in Neutrophils , 2006, Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology.

[14]  Shuzhao Li,et al.  Predicting Network Activity from High Throughput Metabolomics , 2013, PLoS Comput. Biol..

[15]  Eric P. Skaar,et al.  Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus. , 2011, Cell host & microbe.

[16]  J. Ruas,et al.  Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health , 2017, Science.

[17]  R. Knight,et al.  Molecular cartography of the human skin surface in 3D , 2015, Proceedings of the National Academy of Sciences.

[18]  Eric P. Skaar,et al.  Metal Chelation and Inhibition of Bacterial Growth in Tissue Abscesses , 2008, Science.

[19]  Pilar Martín,et al.  The signaling adapter p62 is an important mediator of T helper 2 cell function and allergic airway inflammation , 2006, The EMBO journal.

[20]  Eric P. Skaar,et al.  Imaging mass spectrometry for assessing temporal proteomics: Analysis of calprotectin in Acinetobacter baumannii pulmonary infection , 2014, Proteomics.

[21]  Byong Chul Yoo,et al.  Clinical multi-omics strategies for the effective cancer management. , 2017, Journal of proteomics.

[22]  Weidong Wu,et al.  Zn2+-induced IL-8 expression involves AP-1, JNK, and ERK activities in human airway epithelial cells. , 2006, American journal of physiology. Lung cellular and molecular physiology.

[23]  G. Brumatti,et al.  MK2 Phosphorylates RIPK1 to Prevent TNF-Induced Cell Death , 2017, Molecular cell.

[24]  Elizabeth M. Nolan,et al.  Nickel Sequestration by the Host-Defense Protein Human Calprotectin. , 2017, Journal of the American Chemical Society.

[25]  T. Woodruff,et al.  Is the Complement Activation Product C3a a Proinflammatory Molecule? Re-evaluating the Evidence and the Myth , 2015, The Journal of Immunology.

[26]  K. Lorenz,et al.  Multi-OMICS: a critical technical perspective on integrative lipidomics approaches. , 2017, Biochimica et biophysica acta. Molecular and cell biology of lipids.

[27]  A. Barabasi,et al.  Hierarchical Organization of Modularity in Metabolic Networks , 2002, Science.

[28]  W. Hahn,et al.  Phosphorylation of the tumor suppressor CYLD by the breast cancer oncogene IKKepsilon promotes cell transformation. , 2009, Molecular cell.

[29]  Limsoon Wong,et al.  Why Batch Effects Matter in Omics Data, and How to Avoid Them. , 2017, Trends in biotechnology.

[30]  Richard H. Scheller,et al.  SNARE-mediated membrane fusion , 2001, Nature Reviews Molecular Cell Biology.

[31]  Elizabeth M. Nolan,et al.  Human Calprotectin Is an Iron-Sequestering Host-Defense Protein , 2015, Nature chemical biology.

[32]  José A. Dianes,et al.  2016 update of the PRIDE database and its related tools , 2015, Nucleic Acids Res..

[33]  Markus M. Rinschen,et al.  Altered lipid metabolism in the aging kidney identified by three layered omic analysis , 2016, Aging.

[34]  F. Hughson,et al.  SNARE protein structure and function. , 2003, Annual review of cell and developmental biology.

[35]  Weidong Wu,et al.  Zinc ions as effectors of environmental oxidative lung injury. , 2012, Free radical biology & medicine.

[36]  J. Flores,et al.  The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. , 2008, Cancer cell.

[37]  J. Simard,et al.  Human S100A9 potentiates IL‐8 production in response to GM‐CSF or fMLP via activation of a different set of transcription factors in neutrophils , 2014, FEBS letters.

[38]  J. Gómez-Ariza,et al.  Omics technologies and their applications to evaluate metal toxicity in mice M. spretus as a bioindicator. , 2014, Journal of proteomics.

[39]  S. Catz,et al.  Molecular mechanisms regulating secretory organelles and endosomes in neutrophils and their implications for inflammation , 2016, Immunological reviews.

[40]  Wonku Kang,et al.  Integrative analysis of proteomic and transcriptomic data for identification of pathways related to simvastatin‐induced hepatotoxicity , 2013, Proteomics.

[41]  Vinay Tergaonkar,et al.  Noncanonical NF-κB Signaling in Health and Disease. , 2016, Trends in molecular medicine.

[42]  A. Pineda-Lucena,et al.  GSK3-SCFFBXW7 targets JunB for degradation in G2 to preserve chromatid cohesion before anaphase , 2013, Oncogene.

[43]  S. Beatson,et al.  'Omic' Approaches to Study Uropathogenic Escherichia coli Virulence. , 2017, Trends in microbiology.

[44]  S. Uh,et al.  Role of S100A9 in the development of neutrophilic inflammation in asthmatics and in a murine model. , 2017, Clinical immunology.

[45]  Sixue Chen,et al.  New nodes and edges in the glucosinolate molecular network revealed by proteomics and metabolomics of Arabidopsis myb28/29 and cyp79B2/B3 glucosinolate mutants. , 2016, Journal of proteomics.

[46]  Ken Itoh,et al.  Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: Protection against reactive oxygen and nitrogen species‐induced cell injury , 2005, FEBS letters.

[47]  S. Saptarshi,et al.  Investigating the immunomodulatory nature of zinc oxide nanoparticles at sub-cytotoxic levels in vitro and after intranasal instillation in vivo , 2015, Journal of Nanobiotechnology.

[48]  Dmitrij Frishman,et al.  PROMPT: a protein mapping and comparison tool , 2006, BMC Bioinformatics.

[49]  Boping Zhou,et al.  BMC Microbiology BioMed Central Methodology article Expression of recombinant Clostridium difficile toxin A and B in Bacillus megaterium , 2008 .

[50]  David M. Brown,et al.  Mechanism of neutrophil activation and toxicity elicited by engineered nanomaterials. , 2015, Toxicology in vitro : an international journal published in association with BIBRA.

[51]  J. Powell,et al.  Differential effects of in vitro zinc treatment on gene expression in peripheral blood mononuclear cells derived from young and elderly individuals. , 2007, Rejuvenation research.

[52]  James C. Pino,et al.  Integrated, High-Throughput, Multiomics Platform Enables Data-Driven Construction of Cellular Responses and Reveals Global Drug Mechanisms of Action. , 2017, Journal of proteome research.

[53]  Juan Antonio Vizcaíno,et al.  The ProteomeXchange consortium in 2017: supporting the cultural change in proteomics public data deposition , 2016, Nucleic Acids Res..

[54]  Young-Mo Kim,et al.  Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism. , 2016, Cell host & microbe.

[55]  Jennifer Y. Zhang,et al.  RNA-Seq and ChIP-Seq reveals SQSTM1/p62 as a key mediator of JunB suppression of NF-κB-dependent inflammation , 2014, The Journal of investigative dermatology.

[56]  Zhijian J. Chen.  Ubiquitin signalling in the NF-κB pathway , 2005, Nature Cell Biology.

[57]  Hideaki Sugawara,et al.  The Sequence Read Archive , 2010, Nucleic Acids Res..

[58]  M. Weller,et al.  An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor , 2011, Nature.

[59]  S. Hubbard,et al.  Integrated multi-omics analyses reveal the pleiotropic nature of the control of gene expression by Puf3p , 2015, Scientific Reports.

[60]  S. Simmons,et al.  Role of H2O2 in the oxidative effects of zinc exposure in human airway epithelial cells , 2014, Redox biology.

[61]  W. Chazin,et al.  Zinc-reversible antimicrobial activity of recombinant calprotectin (migration inhibitory factor-related proteins 8 and 14). , 2000, The Journal of infectious diseases.

[62]  Kazuki Saito,et al.  Integrated omics approaches in plant systems biology. , 2009, Current opinion in chemical biology.

[63]  Paul Wilmes,et al.  A biomolecular isolation framework for eco-systems biology , 2012, The ISME Journal.

[64]  L. Trouw,et al.  Production of complement components by cells of the immune system , 2017, Clinical and experimental immunology.

[65]  O. Fiehn,et al.  Process for the integrated extraction, identification and quantification of metabolites, proteins and RNA to reveal their co‐regulation in biochemical networks , 2004, Proteomics.

[66]  P. Zhao,et al.  Integrating Transcriptomics, Proteomics, and Metabolomics Profiling with System Pharmacology for the Delineation of Long-Term Therapeutic Mechanisms of Bufei Jianpi Formula in Treating COPD , 2017, BioMed research international.

[67]  A. Stromberg,et al.  Zinc Deficiency Induces Vascular Pro-Inflammatory Parameters Associated with NF-κB and PPAR Signaling , 2008, Journal of the American College of Nutrition.