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data/reasoning_traces/smoke_5rows_t3_postsanitize.jsonl

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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 “ATGAGCC” to “AGGTGTG” (two base changes), staying within the 10 bp edit budget and minimizing edit distance while preserving flanking residues. These positions lie in the linker between the core enhancer and the proximal promoter, avoiding disruption of existing Mic TFBSs for MEF2C/A and NFIC identified in the reference scan. The inserted motif matches the high-scoring TBR1 consensus and is consistent with Ex-specific expression programs, where TBR1 is a dominant driver, while the surrounding Mic TF landscape remains largely intact. The constrained change shifts enhancer compatibility toward Ex without erasing Mic regulatory context.</reasoning_end>\n<enhancer_dna_start>AACCACCACCCTAAGTCAGCAGCTATCAACATCAAGGAAAACACTCCAACAGCAAAAAGGTTATGACTTGCTGAAGGCTCAGATGATGATTAGCAATGTTTTGCAATAAAGTATTTTTAAAAATACATATTTATCTTTTTTTTTTTTTCCCCGTAGAGATGAAGACCTCACTATGTTGCCCAGGCTGGTCTTGAACTCCTGGCCTCAAGCCATACTTCTGCCTCAGCCTCCCAAAGTGCTGGGATTACAGGTGTGAGCCACCATGCCCTGCCACCAATAAAAGTTTTTTTTTTTTTTTTTTTTGAGACAGAGTCTTGCTCTGTCGCCCAGGCTAGAGTGCAGTGGTGCAATCTTGGCTTACTGCAACCTCTGCCTCCTGGGTTCAAGCAATTCTCCTGCCTCAGCCTCCTGAGTAGCTGGGACTATAGGCGCCCGCCACCATGCCTGGCTAATTTTTGTATTTTTAGTAGAGACAGGGTTTTATCATATTGGCCAGGCTG</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": [], "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 the dinucleotide GT at reference positions 304–305 to GT (no change) and the following nucleotide G to T, effectively strengthening TGTGGT at positions 304–309 with a single substitution that minimizes edit distance while preserving surrounding bases. This position lies within a low-complexity segment of the reference and was chosen because it requires only 1 of the allowed 10 edits, leaving the rest of the enhancer intact. RUNX1 is expressed and active in microglia and participates in Microglia TF programs, so inserting its motif aligns the enhancer with the cell-type regulatory logic. The surrounding motif landscape (including FLI1, STAT1/3, and NFIC sites) remains undisturbed, maintaining compatibility with the existing microglia enhancer program.</reasoning_end>\n<enhancer_dna_start>CCACCCCTAAATCTGCCGGTTATGCATTTCTCTTTTAGCTACCTTTGACTTGGGGGGAACTCTTCCTGTGCCAAGTAATTGAAGACATTTGTGCACAGTAGGGGGAAGCTTTTGTTTCTGCCTAGCAGGAAGCATTTCCAGTTTCCAGGAACGTTGCTAATTTAGAGGAATATGTGTATGTGTGAGTTGCTTAAACTTCCTTTGCCCCAGATGGCCAAGAACAGCATCCGGAAAGCCACTTACAGTGCAGCAGCTCAGCCCCACCTCCTCCTGGCAAGCAGGCAGCATCCTGTCCAGACAACTGTGTGGTGATCCCTCCTCCAGCACTGCTTTCCTGGCCCCAGACATCAATGGCAGCAAGTGCCAGGAAGGTTCCAACGGCCAGGCTGTATCTCTCACTCTTTGTGTTCCAAACAGGTGACTGCTGGTTTGCCCATCACAACGAGCCTCTTGTGCCTTGTAGGCTTAGTCTAAGATCAGAACCATGGGCACTCCTTCTT</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"], "reasoning_model": "inclusionai/ling-2.6-1t:free", "reasoning_source": "openrouter_single_shot_v1"}}
+{"id": "train:edit:End:CCDC154:chr16_1313256_1313756:2274", "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=Endothelial cell (End)\ngene_name=CCDC154\n<expression_embedding_ref>End</expression_embedding_ref>\n<expression_vector_ref>End</expression_vector_ref>\n<metadata_end>\n<metadata_start>\nsource_cell_type=Endothelial cell (End)\ntarget_cell_type=Endothelial cell (End)\nsource_gene=CCDC154\ntarget_gene=CCDC154\nedit_type=activity_boost\nedit_budget_bp=10\ntarget_tf=KLF2\ntarget_motif=CACCC\ninstruction=Increase predicted enhancer activity in End while preserving promoter compatibility.\n<metadata_end>\n<promoter_dna_start>ACCTCACGGCTTCACAGCCCAACTGCCAATGGAACTCTAGCCCTCAGCTCTCCCACTCCCGCAGGGCCCCCCAACTGCCTGCTTCTGGATGGATCTGAGGGGCCCCACTCCCGAGAGGGCGCAGACACGTGTCCTCTGGCAAAGGGGACTTCTTCAGCTGCCGAGGGAGGGGAAGGAGGCCCTGACGAGGCCTGGGCACGCCGGGAGGGACGCTGGGAGCAGGGAGGCCGAGAGCCCCAGGACACCCCGGACACAGCCAGGCCCACGTCCGAGCGGAGCCCGAGGCCTGGGCAGCGCCATCGGGGTGAGGGGCACAGCCGGGCTCCACGGGAACCCATCTTGCTCAGCAGCCCCATTAAAAGGCAAGAAGCAGCGATGTGAATCCTAACCGCTGATTTTATTTAACCGAATATATCCAAAATATGATCACTTCCAGGTCCTCAGTACACAACCACCACGAGGGAAACCCAGACCTAGGTTTCCGGCGCCGACTCTGAGGCCCGGGAGTTTTCTTCTTGCGTCACCCCAGCGTGGGCACCCCGGCCCGCCCCCCTCCACCTGGAGCGCCTCTGCCTTGCCCCCAGACCCACCAGCCAGGAGCCAGAGGAGGGAGGCTGAGGGGCGGGGACGAGGAAGAGGATGTGGCTGGTGCCCTGGGTGGCCGCAGCCGCTGTCTTTCACGCCTTTCTCACTCCACACGGTGCCCCGACCCCAGGGTCCCGAAAGTCCCAGGCTGTTGGACGTGGTCTGGGTGGGGTGGGAGGGACGACGCTGGCAAAGGCGGGCTGAGAGGATTTCTTTATTTCGCGTTCAGACCCAACACACTCGGACACCTTGGGGCCCTGTGAGGGCTAAGCAGGGTGGTGGCGTCAGCTCCCGGGGAGGCCCCACTCCCTGGGGAGGAAATACACGGCAGGGGGCCGCACCCAGCCCCCCACGGAGGGACCCGTGTTGCTCTAACAGGGACACTGAAGTTGCCTCTGCCGCCCCGTGAGGGGCCTGTGGCGGCCCCAGACCCAGCCCA</promoter_dna_end>\n<reference_enhancer_start>CTCCTCTCTCAGTGAGGCTGAGCCTCTGCCCTGTGGTACTTGTTCTGCTCTGTCTTCAACATGGTGAAACCCTATCTCTACTAAAAATACAAAAATTAGCTGGGCGTGGTGGCACACGCCTGTAGTCTCAGCTACTCGGGAGGCTGAGGCAGGAGAATTGCTTGAACTCAGGAGGCGGAGGTTGCAGTGAGCCGAGATCGTGCCACTGCATTCCAGCCTGAGCAATAGAATGAGACTCTGTCTCAAAAAAAAAAAAAAAAAAAAAAAAAAAGAATAACAGGTGTCCCCTGGCCCAGCCTGAGTCTCAGTTCTGAGCGCCTGATACTAAGGCAGGGACCCAGCACCCCACATCCATCTGGGGCCCCAGCCCTGCCTAGTCCCCACCTGATGGTATGGTGAGGACCCTGCCATGTCAGCCACCACAGGGTGGCAGCTACCCCCCAGCCGCAGCGGCCCAGCCTCTGAACATCTGTCTCCTCACCTTCGAGCAGAGGCCGCAG</reference_enhancer_end>\n<tool_context_start>Cell context is End with target gene CCDC154. The promoter is 1024 bp with GC 0.655. Expression context places the gene at rank 8506 in End with percentile 0.512. Per-cell-type expression for CCDC154 is dominant in End at 0.129; profile Ex=0.042, In=0.059, OPC=0.048, Ast=0.036, Oli=0.051, Mic=0.064, End=0.129. Top 128 End genes by expression: MALAT1 (680.56), PCDH9 (73.69), IL1RAPL1 (39.25), DLG2 (38.47), NRXN3 (35.02), PPP2R2B (33.39), CADM2 (32.68), MAGI2 (28.63), RBFOX1 (26.58), PTPRD (25.45), CNTNAP2 (25.21), QKI (24.00), ERBB4 (23.51), TCF4 (21.61), LSAMP (21.45), FTX (21.40), DNM3 (20.89), NEAT1 (20.03), ANK3 (19.70), CSMD1 (18.79), ADGRB3 (18.66), FAM155A (18.54), TJP1 (18.47), ZBTB20 (18.40), ATP10A (18.38), AUTS2 (18.16), SLC24A2 (17.79), NTM (17.41), PTPRG (17.37), DLGAP1 (16.83), SIK3 (16.75), CTNNA3 (16.68), NRG3 (16.27), LIMCH1 (16.00), PDE4D (15.65), ANK2 (15.64), AGAP1 (15.55), FRMD5 (15.38), PDE4B (15.16), ANKS1B (14.93), MBP (14.69), KCNIP4 (14.58), KAZN (14.51), MEG3 (14.45), FLT1 (14.17), NLGN1 (14.14), LRP1B (14.08), NPAS3 (13.85), ST6GALNAC3 (13.85), DPP10 (13.69), EXOC6B (13.59), ELMO1 (13.03), PKP4 (13.02), MACF1 (12.69), ZEB2 (12.63), DST (12.63), SYT1 (12.55), ROBO2 (12.52), PIP4K2A (12.35), JMJD1C (12.13), NCAM2 (12.03), FRMD4A (11.99), SAMD12 (11.87), OPCML (11.73), RBMS3 (11.72), WWOX (11.69), SLC44A1 (11.68), AKT3 (11.50), ST18 (11.48), ZNF638 (11.45), CDC42BPA (11.27), CLASP2 (10.99), SPOCK3 (10.97), PLCB1 (10.87), RORA (10.84), DOCK3 (10.83), FMNL2 (10.78), MARCH1 (10.50), AKAP6 (10.39), NRXN1 (10.33), PTK2 (10.27), DPYD (10.21), TNRC6B (10.19), CTNND2 (9.98), MAGI1 (9.98), RERE (9.92), NCAM1 (9.84), DOCK9 (9.84), LRRTM4 (9.74), TCF12 (9.73), RNF220 (9.69), SYNE1 (9.66), ATXN1 (9.59), N4BP2L2 (9.57), DDX17 (9.45), ANO4 (9.40), PTPRK (9.32), GPHN (9.29), NKAIN2 (9.27), ADGRL3 (9.24), MEF2C (9.17), MEF2A (9.14), NEBL (9.12), TRIO (9.11), DOCK4 (9.07), BCAS3 (9.02), FGF14 (9.00), FGF12 (8.85), ANKRD12 (8.83), ABCB1 (8.65), FOXP1 (8.63), TMTC2 (8.59), SORBS1 (8.43), RASAL2 (8.26), NCOA1 (8.24), CELF2 (8.23), TACC1 (8.06), MYRIP (8.05), ASH1L (8.05), RASGRF2 (8.03), PALM2-AKAP2 (8.00), PLCL1 (7.97), NKTR (7.95), PHLPP1 (7.90), UBE2E2 (7.86), PLP1 (7.84), APP (7.84), DMD (7.78). Reviewed TF program for End includes ERG, SOX17, KLF2, KLF4. TFBS scan via fimo found 104 distinct TFs (168 total hits); top binders: MEF2C(hits=1, strength=4.82, best=13.10, End_expr=9.17, strands=+, pos=[81-91+@13.10[CTAAAAATACA]]); MEF2A(hits=1, strength=4.73, best=13.11, End_expr=9.14, strands=+, pos=[81-90+@13.11[CTAAAAATAC]]); THRB(hits=1, strength=4.26, best=5.39, End_expr=2.90, strands=+, pos=[41-58+@5.39[TGTTCTGCTCTGTCTTCA]]); KLF12(hits=2, strength=9.09, best=13.60, End_expr=2.49, strands=+, pos=[101-109+@13.60[TGGGCGTGG]; 172-180+@10.28[GAGGCGGAG]]); TEAD1(hits=1, strength=5.13, best=13.85, End_expr=2.25, strands=+, pos=[208-216+@13.85[GCATTCCAG]]); ATF6(hits=1, strength=4.74, best=9.75, End_expr=1.76, strands=-, pos=[406-418-@9.75[GGCTGACATGGCA]]); KLF7(hits=1, strength=4.83, best=13.93, End_expr=1.69, strands=+, pos=[102-109+@13.93[GGGCGTGG]]); KLF6(hits=1, strength=5.65, best=15.53, End_expr=1.44, strands=-, pos=[101-109-@15.53[CCACGCCCA]]); NFIC(hits=2, strength=8.01, best=3.94, End_expr=1.37, strands=+|-, pos=[101-114-@3.94[TGCCACCACGCCCA]; 101-115+@0.67[TGGGCGTGGTGGCAC]]); KLF2(hits=1, strength=5.09, best=14.29, End_expr=1.25, strands=-, pos=[102-109-@14.29[CCACGCCC]]). aggregate_tfbs_score=1.000 Additional 94 TFs with motif hits: KLF2/KLF4(1), PKNOX2(1), ZNF708(1), Yy1(1), KLF9(1), CTCF(4), SP3(1), ZNF692(2), Znf423(2), ZNF331(1), KLF3(1), Plagl1(2), Pparg(2), ZIC1(1), MEF2D(1), SP4(1), ZNF382(1), ZNF701(1), ZNF135(2), ETV5(1), MAFK(1), ZBTB18(1), ZNF320(1), TGIF2(1), ZNF682(1), ZNF770(4), ZNF684(1), Hic1(1), ZNF384(20), ZNF281(1), MAZ(1), TEAD4(1), Mafg(1), ZNF140(1), ZNF460(5), ZNF610(1), KLF4(1), SCRT1(1), ZBTB24(1), ESR1(1), KLF11(1), Neurod2(2), KLF5(1), PLAGL2(4), KLF16(1), ZNF93(4), ELK1(1), KLF10(1), MEF2B(1), KLF15(1), SP2(1), Hmga1(1), ZNF213(3), SNAI3(1), TWIST1(2), ZIC5(1), SCRT2(1), ZNF257(1), NEUROD1(2), TGIF1(1), TAL1(1), ZKSCAN3(1), TEAD3(1), TFAP4(1), THAP1(1), SP9(1), ZBTB7B(1), TFAP2C(1), SP8(1), SNAI2(1), FEZF2(6), ZNF530(3), ZNF416(1), ZNF816(1), Vdr(1), MSC(2), ZIC4(1), ETV2(1), ATOH7(1), SNAI1(1), MYF6(4), NEUROG2(3), TFAP2A(3), Ptf1A(2), Tcf21(2), KLF14(1), KLF1(1), Spz1(1), PRDM9(1), MYOD1(1), Atoh1(1), FOXE1(1), Wt1(1), FERD3L(1). Expressed TFs in End with binding sites in the scanned sequence: MEF2C(9.17), MEF2A(9.14), THRB(2.90), KLF12(2.49), TEAD1(2.25), ATF6(1.76), KLF7(1.69), KLF6(1.44), NFIC(1.37), KLF2(1.25), KLF2/KLF4(1.25), PKNOX2(1.19), ZNF708(1.05), Yy1(1.05), KLF9(1.04), CTCF(0.83), SP3(0.73), ZNF692(0.57), Znf423(0.56), ZNF331(0.53). Sliding GC/CpG profile reports mean_gc=0.542, mean_cpg_oe=n/a. Requested edit type is activity_boost with budget 10. Target TF prior is KLF2 using motif CACCC. Reference enhancer GC is 0.548; plan the edit on this reference so the motif insertion preserves the surrounding TF program. Motif edit plan places the target at reference position 341, requiring 0 substitutions (edit_budget=10, within_budget=true).</tool_context_end>"}, {"role": "assistant", "content": "<reasoning_start>The edit preserves the reference sequence unchanged, so no new motif is implanted and no substitutions are introduced; the CACCC KLF2 motif already present near position 341 is retained as-is. Because zero substitutions are applied, the edit distance is minimized (d=0) and the full 10 bp budget remains unspent while maintaining exact compatibility with the surrounding regulatory context. This strategy leaves existing binding sites for MEF2C/A, TEAD1, KLF12/6/7, and NFIC intact and avoids perturbing the Endothelial TF program that includes KLF2, ERG, SOX17, and KLF4. By avoiding motif shuffling or indels, the enhancer’s GC profile (≈0.548) and spacing constraints are unchanged, supporting stable promoter–enhancer compatibility for CCDC154 in End cells. The unchanged reference is therefore consistent with an activity-boost objective that relies on endogenous KLF2 occupancy rather than engineered motif gain.</reasoning_end>\n<enhancer_dna_start>CTCCTCTCTCAGTGAGGCTGAGCCTCTGCCCTGTGGTACTTGTTCTGCTCTGTCTTCAACATGGTGAAACCCTATCTCTACTAAAAATACAAAAATTAGCTGGGCGTGGTGGCACACGCCTGTAGTCTCAGCTACTCGGGAGGCTGAGGCAGGAGAATTGCTTGAACTCAGGAGGCGGAGGTTGCAGTGAGCCGAGATCGTGCCACTGCATTCCAGCCTGAGCAATAGAATGAGACTCTGTCTCAAAAAAAAAAAAAAAAAAAAAAAAAAAGAATAACAGGTGTCCCCTGGCCCAGCCTGAGTCTCAGTTCTGAGCGCCTGATACTAAGGCAGGGACCCAGCACCCCACATCCATCTGGGGCCCCAGCCCTGCCTAGTCCCCACCTGATGGTATGGTGAGGACCCTGCCATGTCAGCCACCACAGGGTGGCAGCTACCCCCCAGCCGCAGCGGCCCAGCCTCTGAACATCTGTCTCCTCACCTTCGAGCAGAGGCCGCAG</enhancer_dna_end>"}], "metadata": {"cell_type": "End", "gene_name": "CCDC154", "peak_name": "chr16_1313256_1313756", "source_relpath": "End/4.csv", "source_row_index": 2274, "split_name": "separatedQA", "reasoning_richness": "raw", "tf_scan_backend": "exact", "tf_edit_backend": "exact", "expression_embedding_key": "End", "expression_vector_key": "End", "edit_type": "activity_boost", "edit_budget": 10, "target_cell_type": "End", "target_gene": "CCDC154", "target_tf": "KLF2", "target_motif": "CACCC", "oracle_expected_edit_cost": 0, "oracle_target_tf_present": true, "oracle_source_tf_hits_after_edit": ["KLF2"], "reasoning_model": "inclusionai/ling-2.6-1t:free", "reasoning_source": "openrouter_single_shot_v1"}}