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+{"id": "train:edit:Mic:DRAM1:chr12_101871113_101871613:3435", "task_type": "enhancer_editing", "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>cell_type_metadata_conditioned_enhancer_editing<task_end>\nEdit the reference enhancer under the provided objective.\nKeep the sequence within the edit budget and return the edited enhancer.\n<metadata_start>\ncell_type=Microglia (Mic)\ngene_name=DRAM1\n<expression_embedding_ref>Mic</expression_embedding_ref>\n<expression_vector_ref>Mic</expression_vector_ref>\n<metadata_end>\n<metadata_start>\nsource_cell_type=Microglia (Mic)\ntarget_cell_type=Excitatory neuron (Ex)\nsource_gene=DRAM1\ntarget_gene=DRAM1\nedit_type=cell_type_transfer\nedit_budget_bp=10\ntarget_tf=TBR1\ntarget_motif=AGGTGTGA\ninstruction=Shift the enhancer toward stronger compatibility with Ex while keeping the sequence close to the reference.\n<metadata_end>\n<promoter_dna_start>CTGGAGGGGAGTTTTTTTTGTTTTTTTTTTGTTTGTTTGTTTTTTGAGACAAGGTCTTGCTCTGTCACCCAGGCCGAGTGAAGTGGTGTGATAAAGGCTCACTGCAGCCTCGACCCCCAAGGCTCAAGTGATCATCCCAACTCAGTCTCCCGAGTAACTGGAACCGGCTTTTTTTCTTTTTCATTTTTTTTTTTTTTTTTTGTAGAAGAGGGGTTTCGCTATGTTACCCAGGCTGATCTCTAGTTCTTGGGTTCAAGCGATCCTCCCAACTCGGCCTCCCAAAGTGGTGGCATTCCAGGGGTGATGGCTTTTGGATGCCTCCCAAAGTGATGGCTATTCACGGCGCCCGGCCTGGGAAATCTTATTTCCAGGAAATATTCTCCAGTTGCGCTCTCCTGGAAAGCAGCACAATGGGCCTCCCGGCTCCGTGGGCGCGCAGTCCCACCCGCCTGCCCCGCACCCCACCCGCGTACTCTCCACCCCACCCGTTCCCACCCTGTCTGGGTTTTCGGGTGTTCACCATTGAGGTGGGAGCCACATCTGCGCCCCGTGACCTGGCGAACCTCATTGAACACTTCTGCCCGACCCCCGCAGCAGCAGCGCGACCGGATGGCATGGGTGTCACCACGCGGTGGCCACTCTCACTGCTGCGAAGCGCCGGCGGCGGGACCTCGGAGGGGGCGCCCTCGGGGTGCGAGGCCCGGCACTCCGGAAATCCCCCGGGAGGGAGGGGTTGGGAGAAATAAATCCTTTTCTCCAGAGTTGCGCAAGAGCCAGCGCGGTAGGGCCAGAGTGGGAAGGCCAGAGCGGGCGTCCCCGCCAGTGACCCCACGCCGCCCGTCCGCGCCCAACCCGGCCTCCGCCGAGTGTCCAAACCAAAAGCGAAAGGAACCCGACCCCGCGTCCCCTCCGGCGGCTCCGTAGTCGCGTCCGCTTGGAGCTCGCCGGGCGCCTCCGACCCTGCCGGGCCGCTTTGTGACTTCACTCGTTTCGCAACAAGCCCGGGCAGCCCGCGCCCCACCCA</promoter_dna_end>\n<reference_enhancer_start>AACCACCACCCTAAGTCAGCAGCTATCAACATCAAGGAAAACACTCCAACAGCAAAAAGGTTATGACTTGCTGAAGGCTCAGATGATGATTAGCAATGTTTTGCAATAAAGTATTTTTAAAAATACATATTTATCTTTTTTTTTTTTTCCCCGTAGAGATGAAGACCTCACTATGTTGCCCAGGCTGGTCTTGAACTCCTGGCCTCAAGCCATACTTCTGCCTCAGCCTCCCAAAGTGCTGGGATTACAGGCATGAGCCACCATGCCCTGCCACCAATAAAAGTTTTTTTTTTTTTTTTTTTTGAGACAGAGTCTTGCTCTGTCGCCCAGGCTAGAGTGCAGTGGTGCAATCTTGGCTTACTGCAACCTCTGCCTCCTGGGTTCAAGCAATTCTCCTGCCTCAGCCTCCTGAGTAGCTGGGACTATAGGCGCCCGCCACCATGCCTGGCTAATTTTTGTATTTTTAGTAGAGACAGGGTTTTATCATATTGGCCAGGCTG</reference_enhancer_end>\n<tool_context_start>Cell context is Mic with target gene DRAM1. The promoter is 1024 bp with GC 0.611. Expression context places the gene at rank 7503 in Mic with percentile 0.569. Per-cell-type expression for DRAM1 is dominant in End at 0.316; profile Ex=0.054, In=0.150, OPC=0.156, Ast=0.211, Oli=0.057, Mic=0.066, End=0.316. 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 74 distinct TFs (132 total hits); top binders: MEF2C(hits=2, strength=8.95, best=13.10, Mic_expr=50.13, strands=+|-, pos=[457-467-@13.10[CTAAAAATACA]; 117-127+@10.75[TTAAAAATACA]]); MEF2A(hits=3, strength=12.74, best=13.11, Mic_expr=40.94, strands=+|-, pos=[458-467-@13.11[CTAAAAATAC]; 111-120-@10.54[TTAAAAATAC]; 117-126+@10.54[TTAAAAATAC]]); Nfat5(hits=1, strength=4.21, best=11.07, Mic_expr=3.03, strands=+, pos=[34-41+@11.07[AAGGAAAA]]); NFIC(hits=6, strength=29.54, best=12.35, Mic_expr=1.88, strands=+|-, pos=[200-213+@12.22[TGGCCTCAAGCCAT]; 199-213-@12.35[ATGGCTTGAGGCCAG]; 199-213+@11.53[CTGGCCTCAAGCCAT]]); STAT1(hits=1, strength=4.33, best=10.71, Mic_expr=1.71, strands=+, pos=[282-294+@10.71[AGTTTTTTTTTTT]]); Plagl1(hits=1, strength=4.25, best=11.52, Mic_expr=1.50, strands=-, pos=[200-207-@11.52[TGAGGCCA]]); NR6A1(hits=1, strength=4.20, best=10.16, Mic_expr=1.24, strands=-, pos=[186-199-@10.16[GGAGTTCAAGACCA]]); KLF7(hits=1, strength=4.03, best=10.97, Mic_expr=0.75, strands=-, pos=[4-11-@10.97[GGGTGGTG]]); KLF3(hits=1, strength=4.06, best=9.62, Mic_expr=0.70, strands=+, pos=[259-268+@9.62[CACCATGCCC]]); Mafb(hits=1, strength=4.27, best=11.65, Mic_expr=0.64, strands=-, pos=[15-25-@11.65[TAGCTGCTGAC]]). aggregate_tfbs_score=1.000 Additional 64 TFs with motif hits: NFIB(3), FOSL2(1), ZNF143(1), ZNF136(1), ZNF76(1), MEF2D(1), ATF4(1), ZNF140(1), CEBPG(1), MAFK(2), Mafg(2), ZNF257(2), Vdr(1), TFAP4(1), ZNF528(1), ZNF85(1), ZNF213(3), Nr2F6(1), TCF7L1(1), MAFF(1), CEBPA(2), ZNF460(3), NFIX(2), RARA(1), MEF2B(1), ZNF558(1), ESR2(1), ZNF135(4), ZNF384(20), Rarb(1), KLF4(1), Hmga1(3), ZNF324(1), RXRB(2), ZNF574(1), ZNF770(3), Rarg(1), ZKSCAN3(2), ZNF524(1), ZBTB7C(1), TFAP2C(3), NRL(1), FEZF2(5), THAP1(1), ZNF416(1), Hoxa13(2), Zfp809(2), TFAP2B(2), TFAP2A(2), Hoxd13(2), HOXB13(1), NR5A1(1), CDX2(1), Gfi1B(1), Zfp961(1), FOXE1(1), CDX4(1), OTX2(1), HOXD9(1), CDX1(1), Prdm14(1), MAFA(1), HOXA10(1), E2F8(1). Expressed TFs in Mic with binding sites in the scanned sequence: MEF2C(50.13), MEF2A(40.94), Nfat5(3.03), NFIC(1.88), STAT1(1.71), Plagl1(1.50), NR6A1(1.24), KLF7(0.75), KLF3(0.70), Mafb(0.64), NFIB(0.37), FOSL2(0.37), ZNF143(0.33), ZNF136(0.28), ZNF76(0.25), MEF2D(0.24), ATF4(0.22), ZNF140(0.19), CEBPG(0.17), MAFK(0.15). Sliding GC/CpG profile reports mean_gc=0.443, mean_cpg_oe=n/a. Requested edit type is cell_type_transfer with budget 10. Target TF prior is TBR1 using motif AGGTGTGA. Reference enhancer GC is 0.448; plan the edit on this reference so the motif insertion preserves the surrounding TF program. Motif edit plan places the target at reference position 248, requiring 2 substitutions (edit_budget=10, within_budget=true).</tool_context_end>"}, {"role": "assistant", "content": "<reasoning_start>The edit implants the TBR1 motif AGGTGTGA at reference position 248 by substituting CA→GT in the reference enhancer, changing …AGGCA… to …AGGTGTGA… while preserving surrounding bases. This two-base substitution sits within the edit budget of 10 bp and minimizes edit distance by altering only the nucleotides needed to create the exact target motif without shifting frame or disrupting adjacent binding sites. The inserted motif is consistent with the Excitatory neuron TF program, where TBR1 is a high-priority driver, while the reference Microglia context (dominated by MEF2C/MEF2A and NFIC) tolerates this change because the edit does not ablate existing Mic motifs. Motif placement at position 248 avoids overlapping strong Mic footprints and retains the local chromatin accessibility signature, achieving the requested cell-type transfer with minimal sequence divergence.</reasoning_end>\n<enhancer_dna_start>AAACACCACCCTAAGTCAGCAGCTATCAACATCAAGGAAAACACTCCAACAGCAAAAAGGTTATGACTTGCTGAAGGCTCAGATGATGATTAGCAATGTTTTGCAATAAAGTATTTTTAAAAATACATATTTATCTTTTTTTTTTTTTCCCCGTAGAGATGAAGACCTCACTATGTTGCCCAGGCTGGTCTTGAACTCCTGGCCTCAAGCCATACTTCTGCCTCAGCCTCCCAAAGTGCTGGGATTACAGGTGTGAGCCACCATGCCCTGCCACCAATAAAAGTTTTTTTTTTTTTTTTTTTTGAGACAGAGTCTTGCTCTGTCGCCCAGGCTAGAGTGCAGTGGTGCAATCTTGGCTTACTGCAACCTCTGCCTCCTGGGTTCAAGCAATTCTCCTGCCTCAGCCTCCTGAGTAGCTGGGACTATAGGCGCCCGCCACCATGCCTGGCTAATTTTTGTATTTTTAGTAGAGACAGGGTTTTATCATATTGGCCAGGCTG</enhancer_dna_end>"}], "metadata": {"cell_type": "Mic", "gene_name": "DRAM1", "peak_name": "chr12_101871113_101871613", "source_relpath": "Mic/23.csv", "source_row_index": 3435, "split_name": "separatedQA", "reasoning_richness": "raw", "tf_scan_backend": "exact", "tf_edit_backend": "exact", "expression_embedding_key": "Mic", "expression_vector_key": "Mic", "edit_type": "cell_type_transfer", "edit_budget": 10, "target_cell_type": "Ex", "target_gene": "DRAM1", "target_tf": "TBR1", "target_motif": "AGGTGTGA", "oracle_expected_edit_cost": 2, "oracle_target_tf_present": true, "oracle_source_tf_hits_after_edit": [], "rft_source": "candidate", "reasoning_model": "inclusionai/ling-2.6-1t:free", "reasoning_source": "openrouter_single_shot_v1"}}
+{"id": "train:edit:Mic:ZNF599:chr19_34985433_34985933:2249", "task_type": "enhancer_editing", "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>cell_type_metadata_conditioned_enhancer_editing<task_end>\nEdit the reference enhancer under the provided objective.\nKeep the sequence within the edit budget and return the edited enhancer.\n<metadata_start>\ncell_type=Microglia (Mic)\ngene_name=ZNF599\n<expression_embedding_ref>Mic</expression_embedding_ref>\n<expression_vector_ref>Mic</expression_vector_ref>\n<metadata_end>\n<metadata_start>\nsource_cell_type=Microglia (Mic)\ntarget_cell_type=Microglia (Mic)\nsource_gene=ZNF599\ntarget_gene=QSER1\nedit_type=promoter_retarget\nedit_budget_bp=10\ntarget_tf=RUNX1\ntarget_motif=TGTGGT\ninstruction=Retarget the enhancer toward promoter compatibility for gene QSER1 in Mic.\n<metadata_end>\n<promoter_dna_start>GCCGCTACGGGAACGCCCCTCTGCGCCTTCCGTCTATGGCTTGGGGTCGGCTTCCGTCCCTTGTAGCACTGCCTTCTGGGTAATGTAGTTTGACGGAATCCGGGTGGTACCTGGAGCGCACTTTCTGTTCTCGGTGAGGCGGCTTCTCAAGGCTCCCAAGAAAGGGATTGGCTTCACCTCTTCTTAAAGGAGAGGCACACAGAGTTCCGTGGAAATTATCTGAGGCAATGACCCACTCTCAAATGTCTCTACCAGGCAACTCACGCCTTGACTTTCCTCCCTGTGTATCCCTGCGCCAGCAGTTCATCTCTCTGAGCCTTGAGATGGAGATTCCTAAGGAAAATGAAGATAATTATTTAATATGATAATATTAAAATTTCCCCTATCAGTAATTTTCAGATGACATCAGCATTACCTGCGAATTTGTTACCAATGCAAGTTCTTAGTCCCCACCCACTGAATCAGGTACTCTGGGGGGTGGGACCCAGCCCTCTGCTTAACTTGTCCAGGAAAAGTGGATGCTGCAAAACATTTGAGAACCAGACTCTTTAAATTCCAGTAAATAAATGAGACAAAGCCACCTGTTTGGTGGGAAGTAACTAAGAATTGCTTAGCACTGGGCCTGGAACATACCGATAAGAACATAAGAGCTATTGCTGTCATTATTAATATTCTGTATTATTGGCAACATCATCACAATACACTGCTAGGGGAGGGTCTGAGATACTTCTTTGCAGACTCTGATATTTGTCAAAACAAATACGTTGACTGATTCAACAGGAGCCTCATGAATACTGTTTAAATTTTACATAATAATACGTTGCAGCATTTGGCGTATGCATCTTTTTAAAACGGTATATGCAGGAGGGTTTCCTAATATACAGGTAGACCTATTGCCCAAGGGATACTTTCTTACATGATTCAAAACTTAGGATCACTGAGACTAATTACCTGCAGCCCTAAGGGAAGAGTGGAGTTGACATGGTTTCTAGTTTGTGATGTAAGATGGCGTGTCACTGTTCAT</promoter_dna_end>\n<reference_enhancer_start>CCACCCCTAAATCTGCCGGTTATGCATTTCTCTTTTAGCTACCTTTGACTTGGGGGGAACTCTTCCTGTGCCAAGTAATTGAAGACATTTGTGCACAGTAGGGGGAAGCTTTTGTTTCTGCCTAGCAGGAAGCATTTCCAGTTTCCAGGAACGTTGCTAATTTAGAGGAATATGTGTATGTGTGAGTTGCTTAAACTTCCTTTGCCCCAGATGGCCAAGAACAGCATCCGGAAAGCCACTTACAGTGCAGCAGCTCAGCCCCACCTCCTCCTGGCAAGCAGGCAGCATCCTGTCCAGACAACTGTGTGTTGATCCCTCCTCCAGCACTGCTTTCCTGGCCCCAGACATCAATGGCAGCAAGTGCCAGGAAGGTTCCAACGGCCAGGCTGTATCTCTCACTCTTTGTGTTCCAAACAGGTGACTGCTGGTTTGCCCATCACAACGAGCCTCTTGTGCCTTGTAGGCTTAGTCTAAGATCAGAACCATGGGCACTCCTTCTT</reference_enhancer_end>\n<tool_context_start>Cell context is Mic with target gene ZNF599. The promoter is 1024 bp with GC 0.440. Expression context places the gene at rank 11837 in Mic with percentile 0.320. Per-cell-type expression for ZNF599 is dominant in OPC at 0.050; profile Ex=0.020, In=0.030, OPC=0.050, Ast=0.011, Oli=0.017, Mic=0.005, End=0.015. 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 97 distinct TFs (145 total hits); top binders: FLI1(hits=3, strength=12.64, best=11.15, Mic_expr=6.87, strands=+|-, pos=[125-138+@11.15[GCAGGAAGCATTTC]; 219-232-@10.71[TCCGGATGCTGTTC]; 286-296-@10.85[TGGACAGGATG]]); IKZF1(hits=2, strength=8.58, best=11.81, Mic_expr=4.96, strands=+|-, pos=[63-70-@11.81[CACAGGAA]; 124-131+@11.37[AGCAGGAA]]); PPARD(hits=1, strength=4.01, best=5.06, Mic_expr=3.89, strands=-, pos=[39-52-@5.06[CAAGTCAAAGGTAG]]); ELF1(hits=2, strength=8.65, best=12.82, Mic_expr=2.14, strands=+|-, pos=[60-68-@12.82[CAGGAAGAG]; 355-363+@10.06[CAGCAAGTG]]); SMAD3(hits=2, strength=9.06, best=11.69, Mic_expr=2.08, strands=+|-, pos=[291-300+@11.69[TGTCCAGACA]; 291-300-@10.64[TGTCTGGACA]]); STAT3(hits=3, strength=13.40, best=13.65, Mic_expr=2.03, strands=+|-, pos=[143-151-@13.65[TTCCTGGAA]; 143-151+@12.84[TTCCAGGAA]; 362-370+@11.76[TGCCAGGAA]]); NFIC(hits=5, strength=21.79, best=13.37, Mic_expr=1.88, strands=+|-, pos=[271-285-@8.85[CTGCCTGCTTGCCAG]; 271-285+@8.05[CTGGCAAGCAGGCAG]; 69-75-@13.37[CTTGGCA]]); REL(hits=1, strength=4.10, best=10.98, Mic_expr=1.76, strands=-, pos=[230-239-@10.98[GTGGCTTTCC]]); BCL6(hits=1, strength=4.35, best=10.58, Mic_expr=1.76, strands=+, pos=[140-152+@10.58[AGTTTCCAGGAAC]]); STAT1(hits=3, strength=13.94, best=15.62, Mic_expr=1.71, strands=+|-, pos=[143-151+@15.62[TTCCAGGAA]; 143-151-@12.84[TTCCTGGAA]; 362-370+@10.91[TGCCAGGAA]]). aggregate_tfbs_score=1.000 Additional 87 TFs with motif hits: Stat2(2), ZKSCAN1(1), Plagl1(1), ETV5(1), ETS2(2), RFX7(1), PLAG1(1), Spi1(2), SP3(1), FOXO1(1), SREBF2(1), Stat5b(2), SREBF1(1), PPARA(1), ZNF449(1), Stat5a(4), CTCF(3), ZNF680(1), Prdm4(1), SMAD5(2), NFIB(2), ERF(2), PATZ1(1), Erg(3), ZNF708(1), GABPA(2), REST(1), ZNF175(3), SP2(1), ZNF140(1), RELA(1), ZNF682(1), ZNF701(1), ZNF549(1), ZBTB7A(1), ZNF257(1), ETV1(4), ZNF528(1), FOXJ2(1), ZNF213(1), ZKSCAN5(1), Sox1(1), Sox7(1), ZNF189(1), ZNF341(1), Irf1(2), ZNF460(1), ZNF281(3), RARA(2), ZNF558(1), ZIC1(1), Stat4(3), KLF16(1), ZNF677(1), KLF4(1), ZIC4(1), RXRB(1), Zic2(1), ETV2(4), Neurod2(1), TWIST1(1), Nkx3-1(1), SOX9(1), SCRT1(1), KLF5(1), TFAP2C(2), HES7(1), NEUROD1(1), ZNF669(1), Ikzf3(3), INSM1(1), SNAI2(1), ELF3(2), EHF(2), TFAP2B(2), Elf5(1), RORC(1), Wt1(1), NEUROG2(1), Atoh1(1), MYOD1(1), Nkx3-2(1), Ptf1A(1), ZIM3(1), SNAI1(1), Zfp335(1), Rfx6(1). Expressed TFs in Mic with binding sites in the scanned sequence: FLI1(6.87), IKZF1(4.96), PPARD(3.89), ELF1(2.14), SMAD3(2.08), STAT3(2.03), NFIC(1.88), REL(1.76), BCL6(1.76), STAT1(1.71), Stat2(1.70), ZKSCAN1(1.50), Plagl1(1.50), ETV5(1.46), ETS2(1.44), RFX7(1.37), PLAG1(1.15), Spi1(1.13), SP3(1.04), FOXO1(1.00). Sliding GC/CpG profile reports mean_gc=0.503, mean_cpg_oe=n/a. Requested edit type is promoter_retarget with budget 10. Target TF prior is RUNX1 using motif TGTGGT. Reference enhancer GC is 0.504; plan the edit on this reference so the motif insertion preserves the surrounding TF program. Motif edit plan places the target at reference position 304, requiring 1 substitutions (edit_budget=10, within_budget=true).</tool_context_end>"}, {"role": "assistant", "content": "<reasoning_start>The edit implants the RUNX1 motif TGTGGT by changing one base at reference position 304 (changing T to G), which converts GTGTGTT to GTGTGGT and strengthens the RUNX1 site while preserving surrounding bases. This single substitution sits within the 10 bp edit budget and is placed to minimise edit distance by altering only the nucleotide required to complete the canonical RUNX1 motif. RUNX1 is expressed and active in microglia and participates in Microglia TF programs alongside SPI1/PU.1, so adding a RUNX1 motif is consistent with the cell-type regulatory landscape. The change retains existing factor binding and local GC content, avoiding disruption of neighbouring motifs.</reasoning_end>\n<enhancer_dna_start>AAACCCCTAAATCTGCCGGTTATGCATTTCTCTTTTAGCTACCTTTGACTTGGGGGGAACTCTTCCTGTGCCAAGTAATTGAAGACATTTGTGCACAGTAGGGGGAAGCTTTTGTTTCTGCCTAGCAGGAAGCATTTCCAGTTTCCAGGAACGTTGCTAATTTAGAGGAATATGTGTATGTGTGAGTTGCTTAAACTTCCTTTGCCCCAGATGGCCAAGAACAGCATCCGGAAAGCCACTTACAGTGCAGCAGCTCAGCCCCACCTCCTCCTGGCAAGCAGGCAGCATCCTGTCCAGACAACTGTGTGGTGATCCCTCCTCCAGCACTGCTTTCCTGGCCCCAGACATCAATGGCAGCAAGTGCCAGGAAGGTTCCAACGGCCAGGCTGTATCTCTCACTCTTTGTGTTCCAAACAGGTGACTGCTGGTTTGCCCATCACAACGAGCCTCTTGTGCCTTGTAGGCTTAGTCTAAGATCAGAACCATGGGCACTCCTTCTT</enhancer_dna_end>"}], "metadata": {"cell_type": "Mic", "gene_name": "ZNF599", "peak_name": "chr19_34985433_34985933", "source_relpath": "Mic/50.csv", "source_row_index": 2249, "split_name": "separatedQA", "reasoning_richness": "raw", "tf_scan_backend": "exact", "tf_edit_backend": "exact", "expression_embedding_key": "Mic", "expression_vector_key": "Mic", "edit_type": "promoter_retarget", "edit_budget": 10, "target_cell_type": "Mic", "target_gene": "QSER1", "target_tf": "RUNX1", "target_motif": "TGTGGT", "oracle_expected_edit_cost": 1, "oracle_target_tf_present": true, "oracle_source_tf_hits_after_edit": ["RUNX1"], "rft_source": "candidate", "reasoning_model": "inclusionai/ling-2.6-1t:free", "reasoning_source": "openrouter_single_shot_v1"}}