Review Article

Challenges for Biomarker Discovery in Body Fluids Using SELDI-TOF-MS

Table 1

Factors that impact preanalytical and analytical bias.

Preanalytical bias

Patients informationAge, gender, ethnicity
Disease subtype and/or severity
Medical background
Health background
Smoking status, alcohol intake, diet, other risk factors
Drug treatments
Patient position (seated/standing/lying), daily moment of collection
Type of control (healthy or disease)
Location of sample collection (single or multisite)
Study inclusion and exclusion criteria

Sample characteristicsNumber of individuals
Type (blood, serum, plasma, urine, cerebrospinal fluid, cell lysate, etc.)
Source (banked or prospectively collected)

Sample-handling proceduresCollection protocols (initial processing, procedure, timing, type of anticoagulant, type of tubes, number of sites, etc.)
Storage procedures (time, aliquoting, storage materials, temperature, freeze-thaw cycles, etc.)

Analytical bias

Sample-Processing proceduresFractionation and depletion methods
Processing steps (denaturation, buffer components, delipidation, etc.)
Liquid handling methods (automated or manual, technique, equipment, etc.)

Experimental protocolsArray types
Sample pH and dilution factor
Quantity of sample loading and position on arrays
Sample binding, washing and drying procedures
Matrix addition (type and method)
Instruments settings
Number of instruments, locations
Environmental factors (temperature, humidity percentage)

Data analysis methodsSpectrum processing (baseline subtraction, normalization, alignment, noise reduction, etc.)
Peak labelling
Feature selection, statistical analysis
Classification approaches