Current state of the art for enhancing urine biomarker discovery

ABSTRACT

Introduction: Urine is a highly desirable biospecimen for biomarker analysis because it can be collected recurrently by non-invasive techniques, in relatively large volumes. Urine contains cellular elements, biochemicals, and proteins derived from glomerular filtration of plasma, renal tubule excretion, and urogenital tract secretions that reflect, at a given time point, an individual’s metabolic and pathophysiologic state.

Areas covered: High-resolution mass spectrometry, coupled with state of the art fractionation systems are revealing the plethora of diagnostic/prognostic proteomic information existing within urinary exosomes, glycoproteins, and proteins. Affinity capture pre-processing techniques such as combinatorial peptide ligand libraries and biomarker harvesting hydrogel nanoparticles are enabling measurement/identification of previously undetectable urinary proteins.

Expert commentary: Future challenges in the urinary proteomics field include a) defining either single or multiple, universally applicable data normalization methods for comparing results within and between individual patients/data sets, and b) defining expected urinary protein levels in healthy individuals.

KEYWORDS:

• Biomarker
• combinatorial peptide ligand libraries
• diabetes
• glycoprotein
• hydrogel nanoparticles
• Lyme Disease
• mass spectrometry
• protein
• proteomics
• selected reaction monitoring
• urine

Acknowledgments

This work was supported in part by George Mason University, the National Institutes of Health (NIH) Innovative Molecular Analysis Technologies (IMAT) program through a grant to Lance Liotta (1R33CA173359-01), and a grant from the Gates Foundation to L. Liotta (Nanotrap sensitivity enhancement of LAM in urine). Lance Liotta is Principle Investigator for the IMAT and Gates Foundation grants and kindly provided editorial advice for this manuscript. The funding sources did not have any role in the study design; the collection, analysis and interpretation of data; manuscript preparation; or the decision to submit the paper for publication.

Declaration of interest

VE is an inventor of hydrogel nanoparticle technologies discussed in this article and, as a university employee, may receive patent royalties per university policies. VE and MH receive salary from NIH IMAT grant 1R33CA173359-01.

Additional information

Notes on contributors

Michael Harpole

MH contributed experimental data. MH, JD, and VE wrote the manuscript.

Justin Davis

MH contributed experimental data. MH, JD, and VE wrote the manuscript.

Virginia Espina

MH contributed experimental data. MH, JD, and VE wrote the manuscript.