A Multidimensional Bioinformatic Platform for the Study of Human Response to Surgery.
Journal
Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354
Informations de publication
Date de publication:
01 06 2022
01 06 2022
Historique:
pubmed:
9
3
2022
medline:
1
6
2022
entrez:
8
3
2022
Statut:
ppublish
Résumé
To design and establish a prospective biospecimen repository that integrates multi-omics assays with clinical data to study mechanisms of controlled injury and healing. Elective surgery is an opportunity to understand both the systemic and focal responses accompanying controlled and well-characterized injury to the human body. The overarching goal of this ongoing project is to define stereotypical responses to surgical injury, with the translational purpose of identifying targetable pathways involved in healing and resilience, and variations indicative of aberrant peri-operative outcomes. Clinical data from the electronic medical record combined with large-scale biological data sets derived from blood, urine, fecal matter, and tissue samples are collected prospectively through the peri-operative period on patients undergoing 14 surgeries chosen to represent a range of injury locations and intensities. Specimens are subjected to genomic, transcriptomic, proteomic, and metabolomic assays to describe their genetic, metabolic, immunologic, and microbiome profiles, providing a multidimensional landscape of the human response to injury. The highly multiplexed data generated includes changes in over 28,000 mRNA transcripts, 100 plasma metabolites, 200 urine metabolites, and 400 proteins over the longitudinal course of surgery and recovery. In our initial pilot dataset, we demonstrate the feasibility of collecting high quality multi-omic data at pre- and postoperative time points and are already seeing evidence of physiologic perturbation between timepoints. This repository allows for longitudinal, state-of-the-art geno-mic, transcriptomic, proteomic, metabolomic, immunologic, and clinical data collection and provides a rich and stable infrastructure on which to fuel further biomedical discovery.
Sections du résumé
OBJECTIVE
To design and establish a prospective biospecimen repository that integrates multi-omics assays with clinical data to study mechanisms of controlled injury and healing.
BACKGROUND
Elective surgery is an opportunity to understand both the systemic and focal responses accompanying controlled and well-characterized injury to the human body. The overarching goal of this ongoing project is to define stereotypical responses to surgical injury, with the translational purpose of identifying targetable pathways involved in healing and resilience, and variations indicative of aberrant peri-operative outcomes.
METHODS
Clinical data from the electronic medical record combined with large-scale biological data sets derived from blood, urine, fecal matter, and tissue samples are collected prospectively through the peri-operative period on patients undergoing 14 surgeries chosen to represent a range of injury locations and intensities. Specimens are subjected to genomic, transcriptomic, proteomic, and metabolomic assays to describe their genetic, metabolic, immunologic, and microbiome profiles, providing a multidimensional landscape of the human response to injury.
RESULTS
The highly multiplexed data generated includes changes in over 28,000 mRNA transcripts, 100 plasma metabolites, 200 urine metabolites, and 400 proteins over the longitudinal course of surgery and recovery. In our initial pilot dataset, we demonstrate the feasibility of collecting high quality multi-omic data at pre- and postoperative time points and are already seeing evidence of physiologic perturbation between timepoints.
CONCLUSIONS
This repository allows for longitudinal, state-of-the-art geno-mic, transcriptomic, proteomic, metabolomic, immunologic, and clinical data collection and provides a rich and stable infrastructure on which to fuel further biomedical discovery.
Identifiants
pubmed: 35258509
doi: 10.1097/SLA.0000000000005429
pii: 00000658-202206000-00012
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1094-1102Subventions
Organisme : NIA NIH HHS
ID : P30 AG028716
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002553
Pays : United States
Organisme : NIDDK NIH HHS
ID : P01 DK078669
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117491
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK124723
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA093245
Pays : United States
Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
McCarty CA, Chisholm RL, Chute CG, et al. The eMERGE Network: a consortium of biorepositories linked to electronic medical records data for conducting genomic studies. BMC Med Genomics 2011; 4:13.
Gottesman O, Kuivaniemi H, Tromp G, et al. The Electronic Medical Records and Genomics (eMERGE) Network: past, present, and future. Genet Med 2013; 15:761–771.
Gaziano JM, Concato J, Brophy M, et al. Million Veteran Program: a mega-biobank to study genetic influences on health and disease. J Clin Epidemiol 2016; 70:214–223.
Arges K, Assimes T, Bajaj V, et al. The Project Baseline Health Study: a step towards a broader mission to map human health. NPJ Digit Med 2020; 3:84.
Dewey FE, Murray MF, Overton JD, et al. Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study. Science 2016; 354:aaf6814.
Hazeldine J, Hampson P, Lord JM. The diagnostic and prognostic value of systems biology research in major traumatic and thermal injury: a review. Burns Trauma 2016; 4:33.
Xiao W, Mindrinos MN, Seok J, et al. A genomic storm in critically injured humans. J Exp Med 2011; 208:2581–2590.
Tompkins RG. Genomics of injury: The Glue Grant experience. J Trauma Acute Care Surg 2015; 78:671–686.
Jayaraman SP, Anand RJ, DeAntonio JH, et al. Metabolomics and precision medicine in trauma: the state ofthe field. Shock (Augusta Ga) 2018; 50:5–13.
Forsberg JA, Potter BK, Wagner MB, et al. Lessons of war: turning data into decisions. EBioMedicine 2015; 2:1235–1242.
Belard AMBA, Buchman TPMD, Dente CJMD, et al. The Uniformed Services University's Surgical Critical Care Initiative (SC2i): bringing precision medicine to the critically ill. Mil Med 2018; 183: (Suppl 1): 487–495.
Kaufmann KB, Heinrich S, Staehle HF, et al. Perioperative cytokine profile during lung surgery predicts patients at risk for postoperative complications -a prospective, clinical study. PLoS One 2018; 13:e0199807.
Zarghooni K, Hackenberg RK, Sander G, et al. Suitability of serum cytokine profiling for early diagnosis of implant-associated infections after orthopaedic surgery: a preliminary prospective study. Cytokine 2019; 116:88–96.
Earley ZM, Akhtar S, Green SJ, et al. Burn injury alters the intestinal microbiome and increases gut permeability and bacterial translocation. PLoS One 2015; 10:e0129996.
Howard BM, Kornblith LZ, Christie SA, et al. Characterizing the gut micro-biome in trauma: significant changes in microbial diversity occur early after severe injury. Trauma Surg Acute Care Open 2017; 2:e000108.
Young VB. The role of the microbiome in human health and disease: an introduction for clinicians. BMJ 2017; 356:j831.
The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012; 486:207–214.
Cox LM, Yamanishi S, Sohn J, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 2014; 158:705–721.
Woody SK, Burdick D, Lapp H, et al. Application programming interfaces for knowledge transfer and generation in the life sciences and healthcare. NPJ Digit Med 2020; 3:24.
Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap) – a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42:377–381.
Sudlow C, Gallacher J, Allen N, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 2015; 12:e1001779.
Denny JC, Rutter JL, Goldstein DB, et al. The “All of Us” research program. N Engl J Med 2019; 381:668–676.
Collins R. What makes UK Biobank special? Lancet 2012; 379:1173–1174.
Conroy M, Sellors J, Effingham M, et al. The advantages of UK Biobank's open-access strategy for health research. J Intern Med 2019; 286:389–397.
Huber-Lang M, Lambris JD, Ward PA. Innate immune responses to trauma. Nat Immunol 2018; 19:327–341.
An G, Nieman G, Vodovotz Y. Computational and systems biology in trauma and sepsis: current state and future perspectives. Int J Burns Trauma 2012; 2:1–10.
Cuenca AG, Maier RV, Cuschieri J, et al. The Glue Grant experience: characterizing the post injury genomic response. Eur J Trauma Emerg Surg 2011; 37:549–558.
Jayaraman SP, Anand RJ, DeAntonio JH, et al. Metabolomics and precision medicine in trauma: the state of the field. Shock 2018; 50:5–13.
Finnerty CC, Jeschke MG, Qian WJ, et al. Determination of burn patient outcome by large-scale quantitative discovery proteomics. Crit Care Med 2013; 41:1421–1434.
Warren HS, Elson CM, Hayden DL, et al. A genomic score prognostic of outcome in trauma patients. Mol Med 2009; 15:220–227.
Cuenca AG, Gentile LF, Lopez MC, et al. Development of a genomic metric that can be rapidly used to predict clinical outcome in severely injured trauma patients. Crit Care Med 2013; 41:1175–1185.
Qian WJ, Petritis BO, Kaushal A, et al. Plasma proteome response to severe burn injury revealed by 18O-labeled “universal” reference-based quantitative proteomics. J Proteome Res 2010; 9:4779–4789.
Hazeldine J, Naumann DN, Toman E, et al. Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: a prospective cohort study. PLoS Med 2017; 14:e1002338.
Finnerty CC, Mabvuure NT, Ali A, et al. The surgically induced stress response. JPEN J Parenter Enteral Nutr 2013; 37: (Suppl 5): 21S–29S.
Desborough JP. The stress response to trauma and surgery. Br J Anaesth 2000; 85:109–117.
Kohl BA, Deutschman CS. The inflammatory response to surgery and trauma. Curr Opin Crit Care 2006; 12:325–332.
Giannoudis PV, Dinopoulos H, Chalidis B, et al. Surgical stress response. Injury 2006; 37: (Suppl 5): S3–S9.