Table 1 List of converging functional themes identified by different LLMs for a co-expression gene set (M9.2), from the BloodGen3 repertoire associated with circulating erythroid cells: ALAS2 BCL2L1 BPGM C14ORF45 C1ORF128 CA1 EPB42 FAM46C FECH GMPR GPR146 GYPB GYPE IFITL1 KRT1 MARCH8 NFIX OR2W3 OSBP2 PLEK2 SELENBP1 SLC14A1 SLC4A1 SNCA TMCC2 TMOD1 TNS1 TRIM10 TUBB2A XK
From: Harnessing large language models (LLMs) for candidate gene prioritization and selection
Model | Functional Themes | Associated genes | LLMs’ Comments |
|---|---|---|---|
GPT3.5 | Hemoglobin synthesis and red blood cell function | ALAS2, CA1, EPB42, FECH, GYPB, GYPE, SLC4A1 | These genes are involved in processes related to hemoglobin synthesis, red blood cell membrane stability, and carbon dioxide transport |
| Â | Enzymes and metabolic processes: | BPGM, FECH, GMPR | These genes encode enzymes involved in glycolysis, heme biosynthesis, and purine nucleotide biosynthesis, respectively |
| Â | Cytoskeletal proteins: | KRT1, TUBB2A | These genes encode proteins involved in maintaining the structure and function of the cytoskeleton |
GPT-4 | Erythrocyte development and function | ALAS2, BPGM, EPB42, GYPB, GYPE, SLC4A1, XK, FECH | These genes are all involved in processes related to erythrocyte (red blood cell) development, function, or associated conditions. For example, ALAS2 and FECH are involved in heme biosynthesis, a crucial component of hemoglobin. BPGM, EPB42, SLC4A1, GYPB, GYPE, and XK are directly involved in erythrocyte structure or function, and mutations in these genes can lead to conditions like hereditary spherocytosis, elliptocytosis, or blood group antigen variations |
| Â | Cytoskeleton and cellular structure | TNS1, TMOD1, TUBB2A | These genes are all involved in cytoskeleton formation and function, which is essential for cell shape, division, and movement |
|  | Ubiquitin–proteasome system | MARCH8, TRIM10 | These genes are involved in the ubiquitin–proteasome system, which is essential for protein degradation, cell cycle regulation, and other crucial cellular functions |
Claude | Erythrocyte biology or iron/heme metabolism | ALAS2, FECH, SLC4A1 | ALAS2 and FECH are both involved in porphyrin/heme biosynthesis. SLC4A1 encodes a major anion exchanger in erythrocytes |
| Â | Cytoskeletal or cytoskeleton-associated genes | EPB42, KRT1, TMOD1, TNS1, TUBB2A | These genes encode cytoskeletal proteins like keratins, tubulins, actins |
| Â | Protein binding, degradation or trafficking | MARCH8, TRIM10 | MARCH8 is an E3 ubiquitin ligase involved in protein degradation. TRIM10 is a RING-finger E3 ubiquitin ligase as well that regulates trafficking of GLUT4 glucose transporters |
| Â | Interferon response | IFITL1, SELENBP1 | IFITL1 and SELENBP1 are both interferon-stimulated genes, though they have different functions |
| Â | phospholipid metabolism or vesicle trafficking | OSBP2, PLEK2 | OSBP2 encodes an oxysterol binding protein that regulates lipid metabolism. PLEK2 is involved in regulating vesicle transport |
| Â | GPCR biology | GPR146, SNCA | GPR146 is an orphan GPCR. SNCA encodes alpha-synuclein, which is involved in dopamine neurotransmission and signaling |
Bard | Production of Heme | ALAS2, FECH | ALAS2 and FECH are both involved in the production of heme, which is an essential molecule for many cellular processes |
| Â | Glutathione synthesis | BPGM, GYPB | BPGM and GYPB are both involved in the synthesis of glutathione, which is an antioxidant that protects cells from damage |
| Â | Cell signaling | GPR146, OR2W3 | GPR146 and OR2W3 are both G protein-coupled receptors that bind to specific ligands and signal to the cell |
| Â | Solute carrier genes | SLC14A1, SLC4A1 | SLC14A1 and SLC4A1 are both solute carrier genes that transport essential molecules across cell membranes |