Title:Identification of Diagnosis and Typological Characteristics Associated with Ferroptosis for Ulcerative Colitis via Bioinformatics and Machine Learning
Volume: 24
Issue: 8
Author(s): Weihao Wang, Xujiao Song, Shanshan Ding and Hao Ma*
Affiliation:
- Aesthetic Medical School, Yichun University, Yichun, China
Keywords:
Ulcerative colitis, ferroptosis, infliximab reactivity, diagnostic model, machine learning, FRGs.
Abstract:
Objective: To investigate and validate ferroptosis genes (FRGs) in ulcerative colitis
(UC) for diagnostic, subtype, and biological agent reactivity, with the goal of providing a foundation
for the identification of novel therapeutic targets and the rational use of infliximab in
clinical practice.
Methods: UC datasets and FRGs were selected from the Gene Expression Omnibus (GEO) and
FerrDb databases. WGCNA was used to identify characteristic genes of UC. LASSO and SVM
models were used to discover key FRGs in UC. A nomogram was constructed for diagnosing
UC using logistic regression (LR), We performed internal and external validation for the model.
Furthermore, we constructed a hub-gene-signature prediction model for the effectiveness of infliximab
in treating UC and deployed it on the website. Finally, the hub gene-drug interaction
networks were constructed.
Results: Nineteen ferroptosis-related genes associated with UC were identified through bioinformatics
analysis. FTH1 and GPX4 were two of the down-regulated genes.The seventeen upregulated
genes consisted of DUOX1, DUOX2, SOCS1, LPIN1, QSOX1, TRIM21, IDO1,
SLC7A11, MUC1, HSPA5, SCD, ACSL3, NOS2, PARP9, PARP14, LCN2, and TRIB2. Five
hub genes, including LCN2, QSOX1, MUC1, IDO1, and TRIB2, were acquried via machine
learning. The mean auc of internal validation was 0.964 and 0.965 respectively, after using
cross-validation and bootstrap in the training set based on the 5 hub-gene diagnostic models. In
the external validation set, the AUC reached 0.976 and 0.858. RF model performs best in predicting
infliximab effectiveness. In addition, we identified two ferroptosis subtypes. Cluster A
mostly overlaps with the high-risk score group, with a hyperinflammatory phenotype.
Conclusions: This research indicated that five hub genes related to ferroptosis might be potential
markers in diagnosing and predicting infliximab sensitivity for UC.
