Integration of Genomic and Proteomic Biosignatures Improves the Discrimination of Response to Nanoparticles in a Mouse Model

Details

• Personal Author:
  Jacobs J ; Kisin E ; Murray A ; Pounds J ; Shvedova A ; Teeguarden J ; Varnum S ; Waters K ; Webb-Robertson B ; Zangar R ; Jacobs J ; Kisin E ; Murray A ; Pounds J ; Shvedova A ; Teeguarden J ; Varnum S ; Waters K ; Webb-Robertson B ; Zangar R
• Description:
  Health risks associated with contact and consumption of nanomaterials is largely unknown and a topic of considerable interest to both manufacturers and consumers. We compared the pulmonary response to repeated exposure to singlewalled carbon nanotubes, crocidolite asbestos, and ultrafine carbon black in a mouse model. Biological signatures of exposure were derived using both genome and proteome profiles though high-content analytical platforms, including microarray, global mass spectrometry-based proteomics, and multiplexed protein ELISA microarray. The goal of this study was to derive biomarkers of response from these data streams and to evaluate the screening potential of integrated biosignatures for hazard assessment. We developed a biosignature integration approach that fuses the multiple data sources at a molecular level. Probability models were derived for individual datasets by using partial least squares discriminant analysis and transformed into likelihood values associated with the probability that a particular sample was exposed to one of the defined particles or the control group. The screening potential of each biosignature was then assessed using the probability model to give insight into particle classes that biomarkers may be derived from each data source. Finally, Bayesian statistics were applied to the likelihood probability models to fuse all data streams into a single model. We find that the probability models associated with individual data types can only successfully separate less than 90% of the samples with cross-validation. However, the integrated probability model can nearly perfectly classify all samples. Using this approach, we identified a panel of biosignatures for each particle class with statistical power to predict response to particulates. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Biomarkers Dust Environmental Monitoring Irritants Laboratories Lung Lung Diseases Occupational Health Particulate Matter Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Airborne-dusts Airborne-particles Biological-distribution Biological-effects Biological-function Biological-systems Biological-transport Exposure-assessment Exposure-levels Exposure-methods Laboratory-animals Lung-disorders Lung-function Lung-irritants Molecular-biology Nanotechnology Particle-aerodynamics Particulate-dust Particulates Pulmonary-clearance Pulmonary-disorders Pulmonary-function Pulmonary-system Pulmonary-system-disorders Respiratory-hypersensitivity Respiratory-irritants Respiratory-system-disorders Statistical-analysis

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Abstract or Summary
• Place as Subject:
  OSHA Region 10 ; OSHA Region 3 ; Washington ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Pages in Document:
  53
• Volume:
  108
• Issue:
  1
• NIOSHTIC Number:
  nn:20035236
• Citation:
  Toxicologist 2009 Mar; 108(1):53
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4) ; Carbon (CAS RN 7440-44-0) ; Crocidolite asbestos (CAS RN 12001-28-4) ; Asbestos (CAS RN 1332-21-4) ; Carbon (CAS RN 7440-44-0) ; Crocidolite asbestos (CAS RN 12001-28-4)
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Construction ; Manufacturing ; Construction ; Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:239de846f4828f1a675e2aeb124e79adc0a649a5653f772aeb378bed1109aca26e67ecbf8e7de64ea5054e2e1e204ba3b96d0115e6c00f8bc4878c82ef6d13a4
• Download URL:
  https://stacks.cdc.gov/view/cdc/187156/cdc_187156_DS1.pdf
• File Type:
  [PDF - 1.01 MB ]