DJ-1 deficiency in SH-SY5Y cells reveals dysregulated networks of genes and pathways involved in neuronal function and disease
Bibliographic record
Abstract
Abstract Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting between 2 – 3% of the population aged 65 and older. Although the etiology of idiopathic PD is still to be elucidated, the study of heritable forms of the disease can provide new understanding into disease mechanisms. Recessively inherited loss of function mutations in the PARK7/DJ-1 gene has been found to be causative for familial, early-onset PD. Importantly, PARK7/DJ-1 related forms of familial PD replicate common disease phenotypes seen in idiopathic PD, including degeneration of substantia nigra dopaminergic neurons, and Parkinsonism. In this study, we evaluate the loss of function of PARK7/DJ-1 on a human neuronal cell line, SH-SY5Y. Following ablation of the PARK7/DJ-1 gene via CRISPR-Cas9, RNA sequencing and the DESEQ2 tool kit were utilized to filter differentially expressed genes between PARK7/DJ-1 knockouts and control SH- SY5Y cells. 5684 genes were identified to be significantly differentially expressed. 3 genes from each of the top 10 upregulated (ATOH8, LAYN, TLX2) and downregulated (CACNA1B, CPLX2, SV2C) gene lists were selected and confirmed via RT-PCR. Differentially expressed gene lists were run through the WebGestalt functional enrichment analysis toolkit to identify enriched gene ontology (GO) terms for biological processes, cellular components, molecular function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways respectively. Among the top 10 significantly enriched KEGG pathways for upregulated genes were those related to neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease (p-adj ≤ 0.05). Differentially expressed genes were run through the STRING database to predict protein-protein interactions (PPI). A highly significant PPI enrichment was observed (p < 1.0e-16). Our results indicate that loss of DJ-1 function in human neuronal cells leads to dysregulation of networks of connected genes and pathways that are implicated in neurodegenerative disease as well as neuronal function.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 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".