Redefining the Practical Utility of Blood Transcriptome Biomarkers in Inflammatory Bowel Diseases

Abstract

Background and Aims The study investigates the practical utility of whole-blood gene expression profiling to diagnose inflammatory bowel diseases [IBDs]. Methods The discovery cohorts included 102 and 51 paediatric IBD patients and controls, and 95 and 46 adult IBD patients and controls, respectively. The replication cohorts included 447 and 76 paediatric IBD patients and controls, and 271 and 108 adult IBD patients and controls, respectively. In the discovery phase, RNA samples extracted from whole peripheral blood were analysed using RNA-Seq, and the predictive values of selected biomarkers were validated using quantitative polymerase chain reaction [qPCR]. Results In all, 15 differentially expressed transcripts [adjusted p ≤0.05] were selected from the discovery sequencing datasets. The receiver operating characteristic curves and area under the curve [ROC-AUC] in replication analyses showed high discriminative power [AUC range, 0.91–0.98] for 11 mRNAs in paediatric patients with active IBD. By contrast, the AUC-ROC values ranged from 0.63 to 0.75 in comparison among inactive paediatric IBDs and active/inactive adult IBDs, indicating a lack of discriminative power. The best multi-mRNA diagnostic classifier showed moderate discriminative power [AUC = 0.81] for paediatric inactive IBD, but was not able to discriminate active or inactive adult IBD patients from controls. The AUC-ROC values did not confirm an ability of the mRNAs abundances to discriminate between active ulcerative colitis and active Crohn’s disease in paediatric or adult populations. Conclusions This study identifies and validates blood transcriptional biomarkers that could be used in clinical settings as diagnostic predictors of IBD clinical activity in paediatric, but not adult, IBD patients.

Integrated Bioinformatics Analysis Identifies ELAVL1 and APP as Candidate Crucial Genes for Crohn’s Disease

“…Furthermore, we analysed an AmpliSeq study (PRJEB28822) in the whole peripheral blood of IBD patients [ 21 ]. APP expression was significantly reduced in pediatric IBD patients compared with HC (FC = −0.54, p < 0.001), while ELAVL1 was significantly elevated (FC = 0.15, p < 0.05).…”

Phenotyping of Adaptive Immune Responses in Inflammatory Diseases

“…Advances in mapping disease activity, identification of early disease, and therapy-related molecular markers have been made possible by the widespread methodology of bulk RNA-seq, a robust and nowadays inexpensive method of sequencing the transcriptome. Despite the effort, the current number of direct applications of molecular-based disease diagnostic and treatment remains limited (39). One explanation for the poor output of bulk RNA-seq-driven methods is that it solely depicts the transcriptome of a homogeneous and unidentifiable agglomerate of different cell types.…”

Transcriptome profiling of ulcerative colitis mouse model suggests biomarkers and therapeutic targets for human colitis

“…In order to compare our mouse data with data from UC patients, we obtained and processed data from 8 different publicly available studies. [15][16][17][18][19][20][21] A set of SDE genes in colon and blood was obtained by combining the different datasets, requiring each gene to be consistently SDE (padj≤0.05) in at least two datasets. For the small RNA-Seq we only used two datasets and required that each miRNA is SDE (padj≤0.05) in at least one of these datasets.…”

“…In order to obtain reliable sets of SDE genes in human UC and to compare them with mouse in both colon and blood, we identified integrated sets of SDE genes using several public human datasets. For colon, 2 RNA-Seq 18 and 2 microarray studies 19,20 and for blood, 2 RNA-Seq studies 16,17 were used ( Table 2, Supplementary File 8). Human miRNA data for colon was obtained by combining one RNA-Seq and one microarray dataset.…”