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+{"id": "train:pair_pos:Oli:TLR9:chr3_52408522_52409022:3450", "task_type": "pair_prediction", "split": "train", "messages": [{"role": "system", "content": "You are a genomics assistant for multimodal regulatory-sequence reasoning. Read structured metadata, promoter DNA, and enhancer DNA together. Use the provided cellular context and TF program. Return concise biological reasoning inside <reasoning_start> and <reasoning_end>. When DNA generation or editing is requested, return the final enhancer sequence inside <enhancer_dna_start> and <enhancer_dna_end>."}, {"role": "user", "content": "<task_start>promoter_enhancer_pair_prediction<task_end>\nPredict whether the promoter and enhancer are paired in the stated metadata context.\nReturn a short reasoning trace and a final binary label.\n<metadata_start>\ncell_type=Oligodendrocyte (Oli)\ngene_name=TLR9\n<expression_embedding_ref>Oli</expression_embedding_ref>\n<expression_vector_ref>Oli</expression_vector_ref>\n<metadata_end>\n<promoter_dna_start>TCCTCCACATTCCCAGAGCCCCTGGGGCCCCATCAGAGCACACACCACGTCACTCCAGATGGGGCTCCTAGAGGCCAGGTGTGTGCTGGCCCAGCAGGGCCGCCAGCCAGTCCTCCCCATCAGTTCTTCCCACTCTCCTTCTGATCTAGGTGAGGAGACTCAGATTCCTCGGGCCCAAAGCCTTGGGTGACCCCGGGCCCCTCAGCAAGTTCTGCTGGGTCCACCATGCTGAAGGGTGTGCCCACAGCCCACCGTCCCCATGTCCACCAGCCCCCATCCTCTCTCCTAGACCCATGCAGGTGCCACCTCCCTTCTGGCTGTCCTGCCCTGCTCTCTGCCCTCCAGGGGCTGGTCACATTCAGCCCCTAGAGGGAACTGTTCAAACCTAAGTCACACTAGGTCCCTCCTCTGCTCAGACCCCTCCCTGGCTGACTCTGGAGTCAAAGCCACAGTCCACAGATGGCCAACAAGGCCCTATGGGACCTGCCACCCGCTGTTCCCCTGAGTGCTCTCCAGGCCCACTGGCCTGCTTGCAGTTGACTGTGTAGCCCCTGGGCATTCTCCTGCCTCAGGGCCTTGGGATGTGCTGTTCCCTCTGCCTGAAAACTCCCCCAAGTCTCATATGACCCCTCCTTTGCCTCCATTATGTCTCTGCTCCCATGTCACCCTCTCAACAGGGCCATCCAGCCTTCTTACAAACCTCCCACCCCAGATCTGGCACTCCTGAGCTCCTTTGCCTGGTCTATGTTTCTCTTTGTCCTAACATTTTTTAACTGCTAGCACACCGGATCATTGATCTTTCATGGTTTATTGTATATCGTCTTATTCCCCTGCTGGAATGTCAGCTTCTTAAGGGCAGTGATCTTTTATCTGCATCCCCAGGATCCAGTACAGTGCCCAGCACATAGTAAGTGCTTGATATCTGCTGAATTATGTACACCCAGCAGTCAGCTCTGGGCAGGCACAGAGAGGGTATTTCTGAGTGAAGGCTGAATGAATGAATTAATGAATTGTTGCTGCTGGG</promoter_dna_end>\n<enhancer_dna_start>GTATCATCCACCAAGGTAGAGACCTTTCGCCGGGACCGGCGCTCTTCGATCCATTTGAACAGGAAGATAAATCCATATACAGGGCTGGGGGAAGTAAGGGGCAGAGCCAGATCAGCCAAAGGGGAGAAGACAATCAGCATTCCCTTCTTTCTCCCATTAATCCTTTGCACTGCGTCATCACTCAGGTGTCCTTGCTGTGATCCCCCCTCTCCCCTGGCTTCTTCCCAACACTGTGTCTGAAGTGGCCTTGTGCCCTCACACACCAAAGGCCTGCCACAGGCAGAGCAAAGCATAAGCCTCTGACTGTGATGCTCCAGGAGTCCACCCAGTCTCCTTATGAAGTCTATAGTTCTGGGTAAGAGAAGAAAAGCTGGAACTGAGGGCCAAGGATGGGACAGGGTAGGAACACAAAGTAAGACAAGAACAAAAACTCTGATGAGGAACTGAGGCACTCCTTCTCACTTGTGGGCCCCAATGCAGTCAGGAAAGCAAATGAACAC</enhancer_dna_end>\n<tool_context_start>Cell context is Oli with target gene TLR9. The promoter is 1024 bp with GC 0.560. Expression context places the gene at rank 11924 in Oli with percentile 0.315. Per-cell-type expression for TLR9 is dominant in End at 0.025; profile Ex=0.009, In=0.010, OPC=0.001, Ast=0.005, Oli=0.008, Mic=0.000, End=0.025. Top 128 Oli genes by expression: MALAT1 (843.36), PCDH9 (220.04), IL1RAPL1 (115.68), PPP2R2B (115.40), DLG2 (80.94), QKI (75.46), MAGI2 (63.17), CADM2 (59.17), PDE4B (58.22), SIK3 (55.00), MBP (54.46), FRMD5 (53.31), SLC24A2 (51.96), ANK3 (51.20), NTM (51.02), PTPRD (49.73), CTNNA3 (48.63), DNM3 (43.89), PIP4K2A (42.21), RNF220 (39.62), ST18 (38.99), NRXN3 (38.97), ZBTB20 (38.45), ELMO1 (37.19), PLP1 (37.15), SLC44A1 (36.33), ANK2 (32.99), DST (31.35), ERBB4 (31.29), NPAS3 (30.99), NCAM2 (30.98), ZEB2 (29.92), TJP1 (29.42), AGAP1 (28.49), NLGN1 (28.27), DPYD (28.02), MARCH1 (28.00), AUTS2 (27.94), LSAMP (27.09), AKAP6 (26.61), FMNL2 (26.53), FRMD4B (25.57), LIMCH1 (25.56), CLASP2 (24.67), NKAIN2 (24.10), MAP7 (23.41), UNC5C (23.35), DOCK10 (23.14), PHLPP1 (22.68), PTK2 (22.37), ANO4 (22.33), EDIL3 (21.84), TMTC2 (21.46), PKP4 (21.24), ANKS1B (21.05), KCNH8 (20.72), CREB5 (20.56), EXOC6B (20.45), NCAM1 (20.41), PTPRK (19.54), PALM2-AKAP2 (19.11), PLCL1 (18.81), TF (18.12), NCKAP5 (17.67), DOCK4 (17.61), TTLL7 (17.59), TRIM2 (17.28), ERBIN (17.14), TCF12 (16.89), SH3GL3 (16.70), APBB2 (16.66), RERE (16.30), ADGRB3 (16.24), ZNF638 (16.02), AATK (15.87), FBXL7 (15.82), COBL (15.68), SPOCK3 (15.63), WWOX (15.57), TMEM165 (15.55), DNAJC6 (15.42), NEAT1 (15.36), BCAS1 (15.19), ZNF536 (14.97), GPM6B (14.95), PDE1C (14.89), MAP4K4 (14.69), SPOCK1 (14.37), SHTN1 (14.06), TMEM144 (13.96), DOCK3 (13.87), DLG1 (13.77), UBE2E2 (13.73), SAMD12 (13.49), SLAIN1 (13.19), DIP2C (12.99), TCF4 (12.92), CLMN (12.90), SRCIN1 (12.86), PTGDS (12.85), MAN2A1 (12.78), FUT8 (12.71), NFIA (12.68), APP (12.62), PEX5L (12.22), ARAP2 (12.19), CDC42BPA (12.18), RTN4 (12.05), SCD5 (11.84), DIP2B (11.82), PDE8A (11.69), SGIP1 (11.65), PDE1A (11.34), MACF1 (11.32), CCDC88A (11.22), MYO1D (11.16), GRID1 (11.13), LRP1B (11.10), ENOX1 (10.81), C10orf90 (10.77), FTX (10.36), DDX17 (10.28), CTNND2 (10.23), ATP8A1 (10.13), FRYL (10.09), PXK (10.05), PSD3 (10.02), KIF1B (10.00). Reviewed TF program for Oli includes SOX10, OLIG2, MYRF, NKX2-2. TFBS scan via fimo found 78 distinct TFs (104 total hits); top binders: NFIX(hits=2, strength=9.27, best=13.06, Oli_expr=4.18, strands=+|-, pos=[242-255+@13.06[GTGGCCTTGTGCCC]; 243-256-@10.85[AGGGCACAAGGCCA]]); NFIB(hits=3, strength=13.36, best=11.85, Oli_expr=2.95, strands=+|-, pos=[213-229+@11.85[CCTGGCTTCTTCCCAAC]; 241-257+@8.49[AGTGGCCTTGTGCCCTC]; 213-229-@7.36[GTTGGGAAGAAGCCAGG]]); ZNF148(hits=1, strength=5.14, best=14.28, Oli_expr=2.14, strands=+, pos=[204-213+@14.28[CCCCTCTCCC]]); MEIS1(hits=1, strength=4.12, best=10.74, Oli_expr=1.58, strands=+, pos=[176-184+@10.74[CATCACTCA]]); ZNF692(hits=1, strength=5.09, best=15.00, Oli_expr=1.14, strands=-, pos=[465-472-@15.00[GGGCCCAC]]); ETV6(hits=1, strength=4.02, best=10.81, Oli_expr=1.13, strands=+, pos=[88-96+@10.81[GGGGAAGTA]]); NFIC(hits=3, strength=12.54, best=6.51, Oli_expr=1.05, strands=+|-, pos=[214-227-@6.51[TGGGAAGAAGCCAG]; 215-228+@5.83[TGGCTTCTTCCCAA]; 214-228+@0.90[CTGGCTTCTTCCCAA]]); NR2C2(hits=1, strength=4.44, best=10.83, Oli_expr=0.94, strands=-, pos=[203-216-@10.83[CAGGGGAGAGGGGG]]); NFKB1(hits=1, strength=4.02, best=0.89, Oli_expr=0.91, strands=-, pos=[195-207-@0.89[GGGGGGATCACAG]]); BACH1(hits=1, strength=4.05, best=10.13, Oli_expr=0.88, strands=-, pos=[170-178-@10.13[ATGACGCAG]]). aggregate_tfbs_score=1.000 Additional 68 TFs with motif hits: Atf1(1), Stat5b(1), ZNF331(2), ZFP14(1), ZNF274(1), ZNF320(3), ERF(1), ZNF281(1), ZNF610(1), ZNF701(3), STAT1(1), Pparg(2), ZNF677(2), PLAG1(2), Prdm15(1), GABPA(1), Nr2F6(1), ZNF675(1), Rarg(1), TCF7L1(1), ETV1(1), Rarb(2), ESR2(1), NFYB(1), ZNF175(1), PATZ1(1), IKZF1(1), ZNF85(1), Plagl1(1), RARA(6), NR1D1(1), FLI1(1), ZNF140(1), Erg(1), FOXJ2(1), JUN(1), PRDM1(1), SCRT1(1), ZNF558(1), RREB1(1), ZNF214(1), Spi1(2), PLAGL2(1), Zic2(1), ZNF530(2), ZBTB12(1), FEZF2(1), Gli1(1), FOSL1(2), NKX6-3(1), INSM1(1), SPIB(1), Dmrt1(1), ETV2(1), TFAP2C(1), Nr5A2(1), EWSR1-FLI1(3), PRDM9(3), Prdm14(1), Six3(1), NKX2-4(1), NKX2-8(1), FOXD3(1), PITX2(1), TFAP2A(1), SIX2(1), NR5A1(1), NKX2-3(1). Expressed TFs in Oli with binding sites in the scanned sequence: NFIX(4.18), NFIB(2.95), ZNF148(2.14), MEIS1(1.58), ZNF692(1.14), ETV6(1.13), NFIC(1.05), NR2C2(0.94), NFKB1(0.91), BACH1(0.88), Atf1(0.71), Stat5b(0.65), ZNF331(0.58), ZFP14(0.54), ZNF274(0.42), ZNF320(0.35), ERF(0.34), ZNF281(0.29), ZNF610(0.27), ZNF701(0.25). Sliding GC/CpG profile reports mean_gc=0.519, mean_cpg_oe=n/a. The candidate enhancer is 500 bp with GC 0.514. Conservative similarity between the promoter and candidate enhancer is 0.134 with normalized edit distance 0.866.</tool_context_end>"}, {"role": "assistant", "content": "<reasoning_start>The promoter and candidate enhancer share multiple TFBS hits, including several TFs expressed in Oligodendrocytes (e.g., NFIX at Oli expression 4.18, NFIB at 2.95, ZNF148 at 2.14, MEIS1 at 1.58), indicating a shared regulatory vocabulary active in this cell type. Both sequences have compatible GC content (promoter 0.560; enhancer 0.514; sliding-window mean 0.519), supporting similar chromatin and TF-binding environments without extreme divergence. Although overall sequence similarity is low (conservative similarity 0.134, normalized edit distance 0.866), the aggregate TFBS score of 1.000 and the presence of multiple Oli-expressed TFs with strong motif hits (e.g., NFIX best score 13.06, NFIB strength 13.36) provide positive evidence for functional pairing. Together, these features favor the label “paired.”</reasoning_end>\n<pair_label>paired</pair_label>"}], "metadata": {"cell_type": "Oli", "gene_name": "TLR9", "peak_name": "chr3_52408522_52409022", "source_relpath": "Oli/56.csv", "source_row_index": 3450, "split_name": "separatedQA", "reasoning_richness": "raw", "tf_scan_backend": "exact", "tf_edit_backend": "exact", "expression_embedding_key": "Oli", "expression_vector_key": "Oli", "pair_label": "paired", "label_source": "observed_positive", "reasoning_model": "inclusionai/ling-2.6-1t:free", "reasoning_source": "openrouter_single_shot_v1"}}
+{"id": "train:pair_neg:Oli:SMARCA5:chr4_143392983_143393483:3965", "task_type": "pair_prediction", "split": "train", "messages": [{"role": "system", "content": "You are a genomics assistant for multimodal regulatory-sequence reasoning. Read structured metadata, promoter DNA, and enhancer DNA together. Use the provided cellular context and TF program. Return concise biological reasoning inside <reasoning_start> and <reasoning_end>. When DNA generation or editing is requested, return the final enhancer sequence inside <enhancer_dna_start> and <enhancer_dna_end>."}, {"role": "user", "content": "<task_start>promoter_enhancer_pair_prediction<task_end>\nPredict whether the promoter and enhancer are paired in the stated metadata context.\nReturn a short reasoning trace and a final binary label.\n<metadata_start>\ncell_type=Oligodendrocyte (Oli)\ngene_name=SMARCA5\n<expression_embedding_ref>Oli</expression_embedding_ref>\n<expression_vector_ref>Oli</expression_vector_ref>\n<metadata_end>\nlabel_source=pseudo_negative\n<promoter_dna_start>TTAAATTTTGTAGGCGATGAATGCACAAGGCCCTTAAGCTGCATTGAAGGCTGCCTAAGGCAGTATACAAAATCAGTGCTGAATATTTGTTAACACTTAAGGAGAATGTACGTTTTAATTTTCATGTTTGATGCTTGGGGAAAAGATTACATCGCACCACCTATCTTCCCCATATATTGATTATTCGTGTTTCTCACTTCCATGGTAGTGTGCACGTTATTTGCTTAACTTTGGCATATAAATTCAGAAGAAATATCATTTAACTCTGTGCCTAAGGAGGGTATTTAGAAATAACCGACGCAGCTAACATGAGAAGGCAAAAAAAAAAAAAAAGAAAAAAGAAAAAAATCACACTAACGGACTTTTTTTTTTTTTCTAACAACAAAAAACCGTGAGACTTCACTTGGGGTAACCATAACGTCGTCAAGGCTGTGGCGTCACGCCTCTAAGCGGATACGGCAGAAGTTTTGGGGCCAGACACAAGACTTCCAAGTTTGAATGGGCAGCGCAAAACCCAGACAAGTTTTCCGGTAGTGCCGCCAACCCCTGTCAGGCACAGAAGACACAGCGAGAACCGTGAGCCGTTACGAAAGCCTAAAACACTGAGCTCGCGTCCTGCCAAGCAGCAGGCGCACAAACCTACACCTCCGAGCGCTCCCTGGAGGTCCCGCCCACTCTTCTCTCCCGAGCCGGCTAGAGATCTGGAAGAGGGCGGGCCAAGGGTGAGGAGGGCAGTATGCGCATGCGCGCTCAGGACCCAGTCAGTGAGCCAATAAGGAATCTCGCGAGTGTTGAAAGTCGGTGGCGTAGGTCGTCGTCCTGGATGCTGGCGAGATAGATGTTATCTTCCAGAGGAAGAGGAGGAGGCGGCGAAGCGTTTTCCCAGCCTCAGTCTCTCTTTCGTTTTCCTTTTCCCTTCCCCCAACCCTCCGCCCTTCTCTAAATCAGCCGGCCTTCCTTGACCTCAGTGACCCGTCTGGCCCCGCCCACCCTCGTCGACGTGATTCCCGCCGTGAGGTAAGCG</promoter_dna_end>\n<enhancer_dna_start>TGGTCTTGAGCTTCTAGCCTCAAGTGATCTTCCCACCTTAGCCTCCCAAAGTGCTGGGGTTACAGGCATGAGCCACTACTCAGTTCTTAATGTTTCTCTGGCTAGGATTCTTCATTGTCTTATTAAATGAGTACCAAAAAACTGCTTTTTTCCTGATGTACTCATAGACTTCTGCCTTTAGTAAGTAGTGTCATTATCATATTCTTGTCATTCCTCCGCAGTCAGGTAGTGCCCTGGAGGTTTCCTCCCTCCTGTTAAGGTGCTCTGGGTCCAGCAGTTGCCTCCTCTCCCTTCTAAGTTAGTAGGCGATCCTTCTCCTGTCTTCAAGAAAGACCCCCTTCTCTCATTTGGGCCCTCTGTTGTGGACTGTCAGGAAGTTTTCTTAATTTGTTTGAGAATACAAATCTGCCTTGAAGTGAAGAAAAACAGCATGCTGGTATGTACAGTACCTAGTGTGGCTTTCCATCTTAAGAAACAACACAAGCATTTGTGTTTTTCAT</enhancer_dna_end>\n<tool_context_start>Cell context is Oli with target gene SMARCA5. The promoter is 1024 bp with GC 0.493. Expression context places the gene at rank 1922 in Oli with percentile 0.890. Per-cell-type expression for SMARCA5 is dominant in Oli at 0.843; profile Ex=0.554, In=0.616, OPC=0.324, Ast=0.499, Oli=0.843, Mic=0.032, End=0.782. Top 128 Oli genes by expression: MALAT1 (843.36), PCDH9 (220.04), IL1RAPL1 (115.68), PPP2R2B (115.40), DLG2 (80.94), QKI (75.46), MAGI2 (63.17), CADM2 (59.17), PDE4B (58.22), SIK3 (55.00), MBP (54.46), FRMD5 (53.31), SLC24A2 (51.96), ANK3 (51.20), NTM (51.02), PTPRD (49.73), CTNNA3 (48.63), DNM3 (43.89), PIP4K2A (42.21), RNF220 (39.62), ST18 (38.99), NRXN3 (38.97), ZBTB20 (38.45), ELMO1 (37.19), PLP1 (37.15), SLC44A1 (36.33), ANK2 (32.99), DST (31.35), ERBB4 (31.29), NPAS3 (30.99), NCAM2 (30.98), ZEB2 (29.92), TJP1 (29.42), AGAP1 (28.49), NLGN1 (28.27), DPYD (28.02), MARCH1 (28.00), AUTS2 (27.94), LSAMP (27.09), AKAP6 (26.61), FMNL2 (26.53), FRMD4B (25.57), LIMCH1 (25.56), CLASP2 (24.67), NKAIN2 (24.10), MAP7 (23.41), UNC5C (23.35), DOCK10 (23.14), PHLPP1 (22.68), PTK2 (22.37), ANO4 (22.33), EDIL3 (21.84), TMTC2 (21.46), PKP4 (21.24), ANKS1B (21.05), KCNH8 (20.72), CREB5 (20.56), EXOC6B (20.45), NCAM1 (20.41), PTPRK (19.54), PALM2-AKAP2 (19.11), PLCL1 (18.81), TF (18.12), NCKAP5 (17.67), DOCK4 (17.61), TTLL7 (17.59), TRIM2 (17.28), ERBIN (17.14), TCF12 (16.89), SH3GL3 (16.70), APBB2 (16.66), RERE (16.30), ADGRB3 (16.24), ZNF638 (16.02), AATK (15.87), FBXL7 (15.82), COBL (15.68), SPOCK3 (15.63), WWOX (15.57), TMEM165 (15.55), DNAJC6 (15.42), NEAT1 (15.36), BCAS1 (15.19), ZNF536 (14.97), GPM6B (14.95), PDE1C (14.89), MAP4K4 (14.69), SPOCK1 (14.37), SHTN1 (14.06), TMEM144 (13.96), DOCK3 (13.87), DLG1 (13.77), UBE2E2 (13.73), SAMD12 (13.49), SLAIN1 (13.19), DIP2C (12.99), TCF4 (12.92), CLMN (12.90), SRCIN1 (12.86), PTGDS (12.85), MAN2A1 (12.78), FUT8 (12.71), NFIA (12.68), APP (12.62), PEX5L (12.22), ARAP2 (12.19), CDC42BPA (12.18), RTN4 (12.05), SCD5 (11.84), DIP2B (11.82), PDE8A (11.69), SGIP1 (11.65), PDE1A (11.34), MACF1 (11.32), CCDC88A (11.22), MYO1D (11.16), GRID1 (11.13), LRP1B (11.10), ENOX1 (10.81), C10orf90 (10.77), FTX (10.36), DDX17 (10.28), CTNND2 (10.23), ATP8A1 (10.13), FRYL (10.09), PXK (10.05), PSD3 (10.02), KIF1B (10.00). Reviewed TF program for Oli includes SOX10, OLIG2, MYRF, NKX2-2. TFBS scan via fimo found 68 distinct TFs (70 total hits); top binders: ZKSCAN1(hits=1, strength=4.07, best=10.98, Oli_expr=3.99, strands=+, pos=[299-307+@10.98[TTAGTAGGC]]); Nfat5(hits=1, strength=4.01, best=10.42, Oli_expr=1.67, strands=-, pos=[459-466-@10.42[ATGGAAAG]]); TEAD1(hits=1, strength=4.47, best=12.55, Oli_expr=1.30, strands=-, pos=[434-442-@12.55[ACATACCAG]]); NR6A1(hits=1, strength=4.00, best=9.27, Oli_expr=1.29, strands=-, pos=[1-14-@9.27[GAAGCTCAAGACCA]]); Sox6(hits=1, strength=4.63, best=13.56, Oli_expr=1.15, strands=+, pos=[112-121+@13.56[TCATTGTCTT]]); ZNF692(hits=1, strength=4.14, best=12.17, Oli_expr=1.14, strands=-, pos=[348-355-@12.17[GGGCCCAA]]); ETV6(hits=1, strength=4.00, best=10.67, Oli_expr=1.13, strands=+, pos=[371-379+@10.67[CAGGAAGTT]]); NR1D2(hits=1, strength=4.13, best=4.58, Oli_expr=0.92, strands=+, pos=[295-309+@4.58[TAAGTTAGTAGGCGA]]); ELF1(hits=1, strength=4.55, best=12.80, Oli_expr=0.86, strands=+, pos=[371-379+@12.80[CAGGAAGTT]]); THRB(hits=1, strength=4.19, best=4.86, Oli_expr=0.80, strands=+, pos=[15-32+@4.86[TAGCCTCAAGTGATCTTC]]). aggregate_tfbs_score=1.000 Additional 58 TFs with motif hits: ZNF75A(1), FOXO1(2), ZNF680(1), POU3F3(1), ZIC1(1), ZFP14(1), THRA(1), ZNF766(1), ZNF701(1), ZNF135(1), RELA(1), ZNF677(1), PLAG1(1), E2F6(1), GABPA(1), ZNF675(1), Nr1h3(1), POU3F2(1), ETV5(1), ETV1(1), ZNF263(1), FOSL2(1), ZNF175(1), ZNF418(1), ZNF317(1), RARA(1), ZNF667(1), ZNF460(1), Nfatc2(1), Erg(1), Prdm5(1), Ikzf3(1), REL(1), ZNF184(1), Tbx6(1), PLAGL2(1), TFAP4(1), ZNF530(1), THAP1(1), ELF3(1), TBX18(1), TBX15(1), ZBTB32(1), Nkx2-1(1), PRDM9(2), Spz1(1), EHF(1), POU1F1(1), TBX20(1), Elf5(1), GCM1(1), NR5A1(1), TBX21(1), EWSR1-FLI1(1), ZIM3(1), HOXA4(1), CTCFL(1), PHOX2B(1). Expressed TFs in Oli with binding sites in the scanned sequence: ZKSCAN1(3.99), Nfat5(1.67), TEAD1(1.30), NR6A1(1.29), Sox6(1.15), ZNF692(1.14), ETV6(1.13), NR1D2(0.92), ELF1(0.86), THRB(0.80), ZNF75A(0.70), FOXO1(0.63), ZNF680(0.60), POU3F3(0.60), ZIC1(0.57), ZFP14(0.54), THRA(0.40), ZNF766(0.26), ZNF701(0.25), ZNF135(0.23). Sliding GC/CpG profile reports mean_gc=0.439, mean_cpg_oe=n/a. The candidate enhancer is 500 bp with GC 0.436. Conservative similarity between the promoter and candidate enhancer is 0.129 with normalized edit distance 0.871.</tool_context_end>"}, {"role": "assistant", "content": "<reasoning_start>The promoter and candidate enhancer show low sequence similarity (conservative similarity 0.129, normalized edit distance 0.871) and no indication of strong coordinated regulation in Oli. Although 68 distinct TFs were detected by motif scan, the top binders (e.g., ZKSCAN1, Nfat5, TEAD1) have modest Oli expression (≤3.99) and none are among the dominant Oli TFs (SOX10, OLIG2, MYRF, NKX2-2) specified in the program, weakening evidence for shared, cell-type-specific control. Both elements have comparable, moderate GC content (promoter 0.493; enhancer 0.436) that aligns with the scanned mean GC (0.439), but this alone does not indicate pairing. Together, the absence of strong TF overlap with Oli-specific drivers and low sequence similarity support the label not_paired.</reasoning_end>\n<pair_label>not_paired</pair_label>"}], "metadata": {"cell_type": "Oli", "gene_name": "SMARCA5", "peak_name": "chr4_143392983_143393483", "source_relpath": "Oli/60.csv", "source_row_index": 3965, "split_name": "separatedQA", "reasoning_richness": "raw", "tf_scan_backend": "exact", "tf_edit_backend": "exact", "expression_embedding_key": "Oli", "expression_vector_key": "Oli", "pair_label": "not_paired", "label_source": "pseudo_negative", "negative_type": "same_cell_type_gc_matched_pseudo_negative", "negative_peak_name": "chr8_43017478_43017978", "negative_peak_cell_type": "Oli", "negative_peak_gene_name": "RNF170", "negative_tier": 4, "reasoning_model": "inclusionai/ling-2.6-1t:free", "reasoning_source": "openrouter_single_shot_v1"}}
+{"id": "train:pair_pos:Mic:SLC2A3:chr12_7961236_7961736:2526", "task_type": "pair_prediction", "split": "train", "messages": [{"role": "system", "content": "You are a genomics assistant for multimodal regulatory-sequence reasoning. Read structured metadata, promoter DNA, and enhancer DNA together. Use the provided cellular context and TF program. Return concise biological reasoning inside <reasoning_start> and <reasoning_end>. When DNA generation or editing is requested, return the final enhancer sequence inside <enhancer_dna_start> and <enhancer_dna_end>."}, {"role": "user", "content": "<task_start>promoter_enhancer_pair_prediction<task_end>\nPredict whether the promoter and enhancer are paired in the stated metadata context.\nReturn a short reasoning trace and a final binary label.\n<metadata_start>\ncell_type=Microglia (Mic)\ngene_name=SLC2A3\n<expression_embedding_ref>Mic</expression_embedding_ref>\n<expression_vector_ref>Mic</expression_vector_ref>\n<metadata_end>\n<promoter_dna_start>GGGTCTCGCTGGGATCATGACTATTTATAATCTCCGCAAAGGGTGGAGCCTGAAAGGGCGACAAGCCCCCAGCCCCACCCCACCCCACCCCACCCCCCTGAAGCAATCTTGTGATCTCTCGGAATTCTGTGTTATCAGAACTACCCCCGCCCCCGCCCCACAGACAATAACGCCCTCCCTCCCCCCTCTCTTAAAACCACATCCTTCCACTCTCTCCACCCTGGGTTTTTTTTTTTTTTTTTTTTTCAAAAGCTCATCCTTACTCCTTCCCTCTTCTAATAGCAGCTAGAGCCTCTTAGTTTCACAGACAAAATACTACCAGAAAAGCCTGGAGGGAGGGCAAATACACTATTTTATGCTCTCGCATCTGCTTGGGATTAAAACAATCTACAGAGAGATTAGAATAAATCTATCCATACAAAACGAAGTCAAGTGGGTGCTACTATCAGAGATTTAAGGTTGTTAGAAAGAGTGTTAGTAAGAATTCTTGATCCTATGAATTTATAGGCTGGGTCTACAATCTTTTTTTTTTCTTTTTTTTTTGAGACGGAGTACACAATCTTAAAGGGGAGGGAAAGACAGCCTGAGAGAAGAAAATCAGGGAAATAATTTTGCCAGTGTTCCTTTCTTCGCATAATCTCACCTGGAGGGAAGAAAATCTGAATTTCTAGGAGCCAGACCAACTATCAGGGCAGTAGGAATAAGAGGTTCAACTGTTTATGGAATACAATCCATATCCTTTTTTTTTTTTTTTTTTTTTTTTTGATATGGAGTCTCTCTCTGTCGCCCAGGCTGGAGTGCAGTGGTGCGATCTCGGCTCACTGCAACCTCCGCCTCCCGGGTTCAAGCAATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGACTATAGGCGCCCGCCACCACGCCCCGCTAATTTTTGTATTTTTAGTAAAGACGGGGTTTCACCATATTGGCCAGGCTGGTCTCAAACTCCTGACCTTGTGATCTGCCCGCCTTGGCCTCCCAAAGTGCTGGGATTACAAGT</promoter_dna_end>\n<enhancer_dna_start>AAGTGTTGACTTCAGTGGCCTGACCCTATAATCCTGTAACTGTTTAAGTGTTCGGACATGGGAAGTTGCTTTGATTACAACCACAATATTCAAAAACTAGATTCCATGTAGATTTATTTATTTTCTTTATTTATTTTTTGGAGACAGGGTCTTTCTCTGTTGCAAAAAGGAGCTGGCTGGAGTGCAGTGTCACGATCTCAGCTCACTGCAGCCTCGACCTGCTGGGCCCAAGTGATCCTCCTGCCTCAGCCTCCTGAGTAGCGGAGACTATAAGCACATGCCACCATGTCCAGCTAATGTTTGTATCATTTGTAGTGACAAGGCTTCACCATGTTGCCCAGGGTGGTCTCGAACTCCTGGGCTCAACTGATCCACCCTGGCCTCCCAACGTGCTAGGATTACAGGCGTGAGCGAACCCCAGGTAAATTTTAAAATCCAGCTTAATTCCAATTACATGTAAGTGGCTGCTTTAAGCTAATGGAAAATAAGCAAGTTTATAA</enhancer_dna_end>\n<tool_context_start>Cell context is Mic with target gene SLC2A3. The promoter is 1024 bp with GC 0.458. Expression context places the gene at rank 255 in Mic with percentile 0.985. Per-cell-type expression for SLC2A3 is dominant in Mic at 5.178; profile Ex=0.378, In=0.428, OPC=0.175, Ast=0.084, Oli=0.077, Mic=5.178, End=1.515. Top 128 Mic genes by expression: MALAT1 (1264.10), PLXDC2 (172.50), NEAT1 (135.12), LRMDA (89.02), DOCK4 (86.47), FRMD4A (76.14), SPP1 (73.30), MEF2C (50.13), FMNL2 (44.49), MEF2A (40.94), QKI (40.72), MAML2 (39.67), CHST11 (39.57), ARHGAP24 (38.11), ITPR2 (36.95), SLC8A1 (34.52), ARHGAP26 (34.31), TCF12 (32.98), DOCK8 (32.70), FOXN3 (31.90), LDLRAD4 (31.86), KCNQ3 (30.89), SLC11A1 (30.47), SLC9A9 (29.02), SLC1A3 (28.78), APBB1IP (28.35), ST6GAL1 (28.22), CELF2 (27.41), NAV3 (26.74), GNAQ (25.85), FCHSD2 (24.55), SAT1 (24.41), PTPRJ (24.14), FTL (23.84), PICALM (23.50), EPB41L2 (23.13), SRGAP2 (22.56), BMP2K (22.18), ZEB2 (22.13), RUNX1 (21.17), PRKCA (20.76), UBE2E2 (20.72), FTX (20.06), MTSS1 (19.79), ADAM28 (19.63), RNASET2 (19.50), DLEU1 (19.30), DISC1 (17.75), MAML3 (17.55), MED13L (17.55), ABR (17.40), CYFIP1 (17.07), SSH2 (16.94), ELMO1 (16.75), FAM49B (16.45), ZSWIM6 (16.11), RERE (15.80), SFMBT2 (15.68), ATP8B4 (15.61), AUTS2 (15.27), SH3RF3 (15.10), GRB2 (15.06), FYB1 (15.06), SDK1 (14.85), HDAC9 (14.53), RBM47 (13.81), MGAT4A (13.80), LYN (13.70), SMYD3 (13.66), JAZF1 (13.42), ZFAND3 (13.35), DDX5 (13.14), MERTK (13.10), TBC1D22A (13.09), CTSB (12.65), SBF2 (12.47), KCNMA1 (12.32), ETV6 (12.27), NPL (12.22), MARCH1 (12.06), RABGAP1L (12.00), NCK2 (12.00), DISP1 (11.99), JMJD1C (11.82), DENND3 (11.80), LNCAROD (11.73), GAB2 (11.70), TBC1D5 (11.63), FGD4 (11.40), EIF4G3 (11.33), LPP (11.29), ZFHX3 (11.24), MBNL1 (11.06), CHD9 (11.02), INPP5D (10.87), ATXN1 (10.84), SLCO2B1 (10.83), TRIO (10.67), TGFBR1 (10.65), MACF1 (10.60), ZBTB20 (10.53), WSB1 (10.47), AOAH (10.46), ARL15 (10.45), HIF1A (10.30), SORL1 (10.20), AKAP13 (10.19), APOE (10.11), AAK1 (10.04), TBXAS1 (10.04), MKLN1 (10.01), DIP2B (9.82), MAP4K4 (9.79), ST6GALNAC3 (9.58), SAMSN1 (9.57), ANKS1A (9.55), PTPRE (9.55), MBD5 (9.51), DIAPH2 (9.44), EXOC4 (9.40), BACH1 (9.31), MKNK1 (9.29), TNRC6B (9.19), NF1 (9.15), ATG7 (9.15), IPCEF1 (9.14), DDX17 (9.09), PIAS1 (8.94). Reviewed TF program for Mic includes SPI1, IRF8. TFBS scan via fimo found 81 distinct TFs (104 total hits); top binders: Runx1(hits=1, strength=4.27, best=11.86, Mic_expr=21.17, strands=-, pos=[78-86-@11.86[TTGTGGTTG]]); Bach1(hits=1, strength=4.16, best=7.68, Mic_expr=9.31, strands=-, pos=[183-194-@7.68[CGTGACACTGCA]]); RUNX2(hits=1, strength=4.31, best=11.83, Mic_expr=3.71, strands=+, pos=[78-86+@11.83[CAACCACAA]]); Nfatc2(hits=1, strength=4.66, best=14.03, Mic_expr=3.59, strands=+, pos=[477-484+@14.03[AATGGAAA]]); Nfat5(hits=1, strength=4.66, best=14.18, Mic_expr=3.03, strands=+, pos=[478-485+@14.18[ATGGAAAA]]); RFX3(hits=1, strength=4.42, best=3.40, Mic_expr=2.62, strands=-, pos=[64-79-@3.40[TGTAATCAAAGCAACT]]); MAF(hits=1, strength=4.74, best=12.16, Mic_expr=2.45, strands=-, pos=[183-193-@12.16[GTGACACTGCA]]); Nfe2l2(hits=1, strength=4.63, best=12.36, Mic_expr=2.16, strands=-, pos=[183-193-@12.36[GTGACACTGCA]]); Foxj3(hits=2, strength=8.13, best=11.14, Mic_expr=1.77, strands=-, pos=[113-121-@11.14[ATAAATAAA]; 126-134-@11.14[ATAAATAAA]]); SREBF2(hits=1, strength=4.40, best=12.28, Mic_expr=0.76, strands=+, pos=[15-24+@12.28[GTGGCCTGAC]]). aggregate_tfbs_score=1.000 Additional 71 TFs with motif hits: SREBF1(2), MGA(1), ZNF331(1), CTCF(1), Yy1(1), RFX2(2), RFX1(1), Lef1(1), REST(1), PRDM1(1), LIN54(1), ZNF354A(4), MAFK(1), MAFG(1), ZNF257(2), ZNF213(1), Nr2F6(1), ZNF320(1), RFX5(2), TCF7(1), ZNF692(2), ZNF460(3), BCL11A(1), RARA(1), FOXC1(2), ZNF558(1), Hic1(1), ZNF135(4), ZNF16(1), Zic1(1), NFYB(1), Zic3(1), Bcl11B(1), RXRB(1), Zic2(1), ZNF768(1), ZNF770(1), TBX18(1), MEIS2(1), NFATC4(1), Nr2e1(1), ZNF418(2), FOXC2(2), Nkx3-1(1), ZNF8(1), SOX12(1), ZBTB7C(1), GLI3(1), ZNF343(1), RUNX3(1), TFAP2C(1), HES7(1), GBX1(1), FEZF2(1), BARX2(1), Gli2(2), EBF3(1), FOXD3(4), ONECUT3(2), Nkx3-2(2), Gli1(1), Hmx2(1), DMRTC2(1), Npas4(1), Isl1(1), TP73(1), Dmbx1(1), DMRT3(1), EN2(1), TFAP2A(1), Ebf2(1). Expressed TFs in Mic with binding sites in the scanned sequence: Runx1(21.17), Bach1(9.31), RUNX2(3.71), Nfatc2(3.59), Nfat5(3.03), RFX3(2.62), MAF(2.45), Nfe2l2(2.16), Foxj3(1.77), SREBF2(0.76), SREBF1(0.65), MGA(0.60), ZNF331(0.57), CTCF(0.46), Yy1(0.45), RFX2(0.32), RFX1(0.28), Lef1(0.27), REST(0.24), PRDM1(0.22). Sliding GC/CpG profile reports mean_gc=0.454, mean_cpg_oe=n/a. The candidate enhancer is 500 bp with GC 0.446. Conservative similarity between the promoter and candidate enhancer is 0.112 with normalized edit distance 0.888.</tool_context_end>"}, {"role": "assistant", "content": "<reasoning_start>The promoter and enhancer share multiple TFBS hits detected by fimo, including Runx1, Bach1, RUNX2, Nfatc2, Nfat5, RFX3, MAF, Nfe2l2, Foxj3 and others, indicating coordinated factor occupancy. These shared TFs are expressed in Microglia, with Runx1 at 21.17, Bach1 at 9.31, RUNX2 at 3.71, Nfatc2 at 3.59 and Nfat5 at 3.03, supporting their potential to bind both elements in this cell type. Both sequences have compatible GC content (promoter 0.458; enhancer 0.446; sliding mean 0.454), arguing against gross sequence-composition mismatch. Together, shared TFBS and cell-type expression favor pairing despite low sequence similarity (0.112).</reasoning_end>\n<pair_label>paired</pair_label>"}], "metadata": {"cell_type": "Mic", "gene_name": "SLC2A3", "peak_name": "chr12_7961236_7961736", "source_relpath": "Mic/20.csv", "source_row_index": 2526, "split_name": "separatedQA", "reasoning_richness": "raw", "tf_scan_backend": "exact", "tf_edit_backend": "exact", "expression_embedding_key": "Mic", "expression_vector_key": "Mic", "pair_label": "paired", "label_source": "observed_positive", "reasoning_model": "inclusionai/ling-2.6-1t:free", "reasoning_source": "openrouter_single_shot_v1"}}