A semiautomated framework for integrating expert knowledge into disease marker identification.
BACKGROUND
The availability of large complex data sets generated by high throughput technologies has enabled the recent proliferation of disease biomarker studies. However, a recurring problem in deriving biological information from large data sets is how to best incorporate expert knowledge into the biomarker selection process.


OBJECTIVE
To develop a generalizable framework that can incorporate expert knowledge into data-driven processes in a semiautomated way while providing a metric for optimization in a biomarker selection scheme.


METHODS
The framework was implemented as a pipeline consisting of five components for the identification of signatures from integrated clustering (ISIC). Expert knowledge was integrated into the biomarker identification process using the combination of two distinct approaches; a distance-based clustering approach and an expert knowledge-driven functional selection.


RESULTS
The utility of the developed framework ISIC was demonstrated on proteomics data from a study of chronic obstructive pulmonary disease (COPD). Biomarker candidates were identified in a mouse model using ISIC and validated in a study of a human cohort.


CONCLUSIONS
Expert knowledge can be introduced into a biomarker discovery process in different ways to enhance the robustness of selected marker candidates. Developing strategies for extracting orthogonal and robust features from large data sets increases the chances of success in biomarker identification.
Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Jing
J
Wang
Bobbie-Jo M
BJ
Webb-Robertson
Melissa M
MM
Matzke
Susan M
SM
Varnum
Joseph N
JN
Brown
Roderick M
RM
Riensche
Joshua N
JN
Adkins
Jon M
JM
Jacobs
John R
JR
Hoidal
Mary Beth
MB
Scholand
Joel G
JG
Pounds
Michael R
MR
Blackburn
Karin D
KD
Rodland
Jason E
JE
McDermott
D000243:Adenosine Deaminase / Q000097:blood; D000818:Animals; D001499:Bayes Theorem; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016000:Cluster Analysis; D030562:Databases, Protein; D001330:Electronic Data Processing; D006801:Humans; D051379:Mice; D020543:Proteome / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000175:diagnosis
D015415:Biomarkers; D020543:Proteome; C548483:Ada protein, mouse; D000243:Adenosine Deaminase