SPIN: Development of sample-specific protein integrity numbers as an index of biospecimen quality.
It is widely accepted that variable biorepository specimen handling conditions can significantly alter outcomes of clinical research studies, suggesting the need for a metric for sample analyte protein integrity. In line with the National Cancer Institute (NCI) Best Practices, it is vital that the integrity of specimens used for biomarker studies are of the highest standard to ensure validity of the data they generate and confidence in the application of new findings to clinical management. We describe the creation of a program to discover proteins in biorepository samples that can be utilized to assess the integrity of stored specimens for protein-based biomarker studies, similar to the universally accepted quality metric for RNA, the RNA Integrity Number, or RIN. The study mimics potential variation in pre-analytical conditions which may result in proteolysis and other proteome-associated changes and employs surface-enhanced laser desorption time-of-flight mass spectrometry (SELDI-TOF MS) to assess changes in multiple proteins and peptides in a high-throughput manner. Candidate peaks from SELDI spectra of representative sample types (e.g., serum, urine, tissue extracts) which demonstrate differing but reproducible sensitivity to suboptimal processing and storage were selected and quantified in a series of specimens stored in the BioBank within the Beaumont Health System. We then assigned a relative index known here as Sample-specific Protein Integrity Number, or SPIN, which is derived from a ratio of nonstable vs. stable proteins for each sample type in the investigation. This methodology can be applied to every sample type and, once refined and established, the SPIN could be used by any biobank or laboratory using biobanked samples without specialized equipment and irrespective of the sample pre-analytical collection conditions.
1 Beaumont BioBank, Beaumont Health System , Royal Oak, Michigan.
Timothy J
TJ
Geddes
Samreen
S
Ahmed
Barbara L
BL
Pruetz
Dianna M
DM
Larson
Bryan J
BJ
Thibodeau
Jan
J
Akervall
George D
GD
Wilson
D018070:Biological Specimen Banks / Q000592:standards*; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000652:urine; D016000:Cluster Analysis; D006801:Humans; D011506:Proteins / Q000032:analysis*; D011786:Quality Control; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013696:Temperature; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D011506:Proteins