Identification of fibronectin 1 (FN1) and complement component 3 (C3) as immune infiltration-related biomarkers for diabetic nephropathy using integrated bioinformatic analysis
Bibliographic record
Abstract
Immune cell infiltration (ICI) plays a pivotal role in the development of diabetic nephropathy (DN). Evidence suggests that immune-related genes play an important role in the initiation of inflammation and the recruitment of immune cells. However, the underlying mechanisms and immune-related biomarkers in DN have not been elucidated. Therefore, this study aimed to explore immune-related biomarkers in DN and the underlying mechanisms using bioinformatic approaches. In this study, four DN glomerular datasets were downloaded, merged, and divided into training and test cohorts. First, we identified 55 differentially expressed immune-related genes; their biological functions were mainly enriched in leukocyte chemotaxis and neutrophil migration. The CIBERSORT algorithm was then used to evaluate the infiltrated immune cells; macrophages M1/M2, T cells CD8, and resting mast cells were strongly associated with DN. The ICI-related gene modules as well as 25 candidate hub genes were identified to construct a protein-protein interactive network and conduct molecular complex detection using the GOSemSim algorithm. Consequently, FN1, C3, and VEGFC were identified as immune-related biomarkers in DN, and a related transcription factor–miRNA–target network was constructed. Receiver operating characteristic curve analysis was estimated in the test cohort; FN1 and C3 had large area under the curve values (0.837 and 0.824, respectively). Clinical validation showed that FN1 and C3 were negatively related to the glomerular filtration rate in patients with DN. Six potential therapeutic small molecule compounds, such as calyculin, phenamil, and clofazimine, were discovered in the connectivity map. In conclusion, FN1 and C3 are immune-related biomarkers of DN.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".