Interactome Mapping: Using Protein Microarray Technology to Reconstruct Diverse Protein Networks

Uzoma, Ijeoma; Zhu, Heng

The two most common subtypes of inflammatory bowel disease (IBD) are Crohn's disease (CD) and ulcerative colitis (UC). They are idiopathic in nature and are both characterized by an abnormal immunological response in the gut [59] . IBD is clinically thought to have autoimmune etiology, although, anti-microbial antibodies to normal bacteria are present in the sera of patients, leading to the pathogenesis of the disease [8] . The known serological antibodies are currently used as partial diagnostic criteria as they are not robust enough to stand alone [60] . Chen et al. elected to use an E. coli proteome microarray to characterize the differential immune response (serum anti-E. coli antibodies) in patients with CD and UC compared to healthy controls (HC). The microarray included 4256 E. coli proteins, encompassing the vast majority of the proteome of E. coli K12 strain. The sera from HC (n = 29), CD (n = 66) and UC (n = 39) were profiled using this array and the reactive anti-E. coli antibodies were detected with anti-human IgG antibodies. Data analysis revealed differential immunogenic response to 417 proteins between these three groups: 169, 186 and 19 were highly immunogenic in HC, CD and UC, respectively. Two robust sets of novel serological biomarkers were identified that can discriminate CD from HC or UC with >80% overall accuracy and sensitivity [8] . This is the first study to identify serological biomarkers in human immunological diseases with respect to the entire proteome of a microbial species. The underlying molecular pathology of other immune system related diseases can also be examined with this proteome microarray approach.