Table 4 Output generated by GPT-4 pertaining to the prioritization of genes comprised in M9.2 module using two distinct prompting approaches
From: Harnessing large language models (LLMs) for candidate gene prioritization and selection
Approach | Stepwise prompting | Direct prompting |
|---|---|---|
Prompt | Based on the summary provided below, could you select a top candidate based on: relevance to (1) erythroid cells or erythropoiesis, (2) current use as a biomarker, (3) potential use as a blood transcriptional biomarker, (4) relevance to leukocytes immune biology, (5) being a known drug target, and (6) being of therapeutic relevance for immune mediated diseases? Equal weight should be given to each of those 6 criteria: [all fact-checked statements supported by references from Step 5 were inserted here] | For the list of genes provided below, could you select a top candidate based on: relevance to (1) erythroid cells or erythropoiesis, (2) current use as a biomarker, (3) potential use as a blood transcriptional biomarker, (4) relevance to leukocytes immune biology, (5) being a known drug target, and (6) being of therapeutic relevance for immune mediated diseases? Equal weight should be given to each of those 6 criteria. ALAS2 BCL2L1 BPGM C14ORF45 C1ORF128 CA1 EPB42 FAM46C FECH GMPR GPR146 GYPB GYPE IFIT1L KRT1 NFIX OR2W3 OSBP2 PLEK2 SELENBP1 SLC14A1 SLC4A1 SNCA TMCC2 TMOD1 TNS1 TRIM10 TUBB2A XK MARCH8 |
Candidate selected | BCL2L1 | ALAS2 |
GPT-4’s preface | Based on the information provided and weighting all six criteria equally, BCL2L1 (B-cell lymphoma 2-like 1) appears to be the top candidate among the genes described (BCL2L1, ALAS2, SLC4A1, CA1, and FECH). Here's how this gene stacks up against the six criteria: | Based on the given criteria, the top candidate from your provided gene list appears to be ALAS2 |
GPT-4 on criterion 1 | Relevance to erythroid cells or erythropoiesis: BCL2L1 is associated with erythroid cells through its control of apoptosis, though it's not specifically linked to erythropoiesis | Relevance to erythroid cells or erythropoiesis: ALAS2 (delta-aminolevulinate synthase 2) is highly relevant to erythroid cells and erythropoiesis. This enzyme catalyzes the first step in the heme biosynthetic pathway. It's specifically expressed in erythroid cells and mutations in this gene can lead to X-linked sideroblastic anemia |
GPT-4 on criterion 2 | Current use as a biomarker: Although BCL2L1 is not widely used as a biomarker, it could be of interest in certain malignancies due to its key role in apoptosis regulation | Current use as a biomarker: As of my knowledge cut-off in 2021, ALAS2 is not frequently used as a biomarker. However, changes in its expression or mutations in this gene are associated with erythropoietic diseases |
GPT-4 on criterion 3 | Potential use as a blood transcriptional biomarker: BCL2L1, due to its role in apoptosis regulation, has potential as a biomarker for diseases associated with apoptosis dysregulation, including certain cancers | Potential use as a blood transcriptional biomarker: Given its specific expression in erythroid cells, ALAS2 could potentially serve as a blood transcriptional biomarker, particularly in conditions affecting red blood cell formation |
GPT-4 on criterion 4 | Relevance to leukocytes immune biology: BCL2L1 is highly relevant to leukocyte immune biology due to its role in regulating the lifespan and function of immune cells | Relevance to leukocytes immune biology: While not directly involved in leukocyte biology, heme and iron metabolism (in which ALAS2 is involved) can impact immune cell function and overall immune responses |
GPT-4 on criterion 5 | Being a known drug target: BCL2L1 is significant as a target in cancer therapy, with strategies being developed to inhibit its anti-apoptotic function | Being a known drug target: Although not a direct target for drugs, ALAS2 is the target of gene therapy for X-linked sideroblastic anemia, demonstrating therapeutic relevance |
GPT-4 on criterion 6 | Therapeutic relevance for immune mediated diseases: BCL2L1 holds potential therapeutic value for immune-mediated diseases due to its role in regulating apoptosis in lymphocytes | Therapeutic relevance for immune mediated diseases: While not directly relevant to immune-mediated diseases, the role of iron and heme metabolism in immune responses and inflammation indirectly ties ALAS2 to immune disease processes. Additionally, alterations in erythropoiesis and red blood cells can influence immune responses and disease progression |
GPT-4’s conclusive statement | While the other genes listed also meet some of these criteria to varying extents, BCL2L1 appears to be the best fit when considering all criteria equally | So while not all criteria are strongly met, given the specific criteria and the gene list provided, ALAS2 seems the most balanced candidate. The consideration of ALAS2 as the top candidate assumes that the six criteria are independent and weighted equally; changes in weighting or interactions between criteria may affect this selection. Furthermore, updates in our understanding of gene function, disease associations, or biomarker utility after 2021 could also affect this choice |