> 매일 아침 research-watcher가 27개 query family × PubMed/GEO를 스캔해서, Brown Biotech 파이프라인 관점에서 decision-ready 인사이트로 정리합니다. 매일 06:00 KST 자동 생성. **Category focus:** AI Drug Discovery **Published:** 2026-10-03 06:09 KST **Entry ID:** 114 **Tags:** #gse349088 #gse349089 #scRNA-seq-companion-pair #AML #acute-myeloid-leukemia #refractory-AML #venetoclax #ABT-199 #Venclexta #BCL2-inhibitor #BCL2-family #BCL-XL --- ## 🔬 Today's Top Findings ### 1. [Clinical & Regulatory + Refractory Acute Myeloid Leukemia (AML) + ERK1/2-Drp1-Mcl-1 Mitochondrial Fission Axis + Venetoclax Resistance Mechanism + First NOVEL Paired scRNA-Seq Companion Cohort of the Day] ERK1/2 Inhibition Overcomes Resistance to Venetoclax in AML by Inhibiting Drp1-Dependent Mitochondrial Fission and Destabilizing Mcl-1 [scRNA-Seq 1 + scRNA-Seq 2] (GSE349088 + GSE349089, score 6 each, n=14 + n=6 = 20 paired-assay companion, Homo sapiens, pdat 2026/09/30 = 3 days ago = FRESHEST pair of the day, raw H5 files, Expression profiling by scRNA-seq-via-10x-Genomics-Chromium, the ONLY paired-companion AML-ERK1/2-Drp1-Mcl-1-Venetoclax-resistance scRNA-seq atlas in the entire 2026-10-03 hits.jsonl and the FIRST NOVEL AML-Venetoclax-resistance / ERK1/2-Drp1-mitochondrial-fission / Mcl-1-destabilization atlas to surface in the prior id:108-id:113 retention window — a direct bioinformatics + AI-DD + refractory-AML + BCL2-inhibitor-resistance + mitochondrial-dynamics-target + venetoclax-ABT-199-combination-strategy input for the BB AI-DD + clinical-translational lane with explicit overlap to the BCL2-BCL-XL-BCL-W-family / venetoclax-ABT-199-Venclexta-FDA-approved-2016-AML-CLL / navitoclax-ABT-263-BCL2-BCL-XL / obatoclax-GX15-070 / BCL2-mimetic-AZD0466-liposomal-derivative / DRP1-DNM1L-dynamin-related-protein-1 / mitochondrial-fission-fusion-MFN1-MFN2-OPA1 / Mcl-1-MCL1-myeloid-cell-leukemia-1 / ERK1-ERK2-MAPK-pathway-MAP2K1-MAP2K2 / MEK-inhibitor-trametinib-Mekinist-cobimetinib-Cotellic-binimetinib-Mektovi / MEK-inhibitor-Venetoclax-combination-Phase-1-2 / AML-acute-myeloid-leukemia-elderly-unfit-intensive-chemotherapy / AML-de-novo-secondary-therapy-related / AML-FLT3-ITD-FLT3-TKD-mutation-midostaurin-Rydapt-gilteritinib-Xospata-quizartinib-Vanflyta / AML-IDH1-IDH2-ivosidenib-Tibsovo-enasidenib-Idhifa-olutasidenib-Rezlidhia / AML-DNMT3A-NPM1-TET2-mutated-elderly / AML-venetoclax-azacitidine-azacitidine-venetoclax-VEN-AZA-FDA-approved-2020-elderly-AML / AML-venetoclax-low-dose-cytarabine-LDAC / AML-relapsed-refractory-R-R-AML / AML-stem-cell-LSC-CD34-CD38-CD123-CD33-CD45RA / tumor-microenvironment-bone-marrow-niche-hypoxic / reactive-oxygen-species-ROS-mitochondrial-membrane-potential-DYMP-DILOC2-JC1 / BCL2-Mcl-1-protein-protein-interaction-PPI / mitochondrial-apoptosis-intrinsic-pathway-BAX-BAK-VDAC / AML-WBC-blast-count-complete-remission-CR-CR-MRD-minimal-residual-disease-flow lanes) ### 2. [AI Drug Discovery + Refractory Glioblastoma Multiforme GBM + KAT7-H3K14ac-RAC2 Acetyltransferase Epigenetic Axis + OXPHOS Metabolic Stemness Maintenance + First NOVEL GBM KAT7-Acetyltransferase ChIP-Seq Companion of the Day] Targeting the KAT7/H3K14ac/RAC2 Axis Mediates OXPHOS to Promote Stemness Maintenance and Malignancy in Glioblastoma [RNA-Seq + ChIP-Seq] (GSE328130 + GSE328308, score 6 each, n=6 + n=8 = 14 paired-assay companion, Homo sapiens, pdat 2026/09/16 = 17 days ago, raw TXT + BED files, Expression profiling by RNA-seq-via-illumina-NovaSeq + ChIP-Seq-anti-H3K14ac-anti-KAT7, the ONLY paired-companion GBM-KAT7/H3K14ac/RAC2-OXPHOS-stemness atlas in the entire 2026-10-03 hits.jsonl and the FIRST NOVEL GBM-KAT7-acetyltransferase + H3K14ac-histone-mark + RAC2-NADPH-oxidase-OXPHOS-stemness atlas to surface in the prior id:108-id:113 retention window — a direct AI-DD + refractory-GBM + histone-acetyltransferase-inhibitor + epigenetic-therapy + OXPHOS-metabolic-stemness input for the BB AI-DD + clinical-translational lane with explicit overlap to the KAT7-HBO1-MYST2-histone-acetyltransferase / H3K14ac-histone-3-lysine-14-acetylation-active-chromatin-mark / RAC2-Ras-related-C3-botulinum-toxin-substrate-2-NADPH-oxidase-NOX2-complex-p47phox-p67phox / OXPHOS-oxidative-phosphorylation-mitochondrial-electron-transport-chain-complex-I-III-IV-V / GBM-glioma-stem-cell-GSC-SOX2-NESTIN-CD133-OCT4-NANOG / GBM-proneural-Mesenchymal-classical-neural-Verhaak-subtype / GBM-IDH1-R132H-IDH2-R172K-wildtype-primary / GBM-EGFRvIII-amplified-PTEN-loss-TERT-promoter / GBM-temozolomide-TMZ-Stupp-protocol + TMZ-resistance / GBM-radiotherapy-XRT-TTFields-Optune / GBM-bevacizumab-Avastin-anti-VEGF-recurrent / GBM-regorafenib-Stivarga-multi-kinase / GBM-tumor-microenvironment-GMB-TME / GBM-macrophage-microglia-MDM2-STAT3-TAM / KAT7-inhibitor-WM-3835-WM-1119-cyclic-peptide / HBO1-inhibitor-PF-1 / MYST-family-acetyltransferase-inhibitor / histone-acetyltransferase-p300-CBP-bromodomain-BET-inhibitor-JQ1-OTX015 / stemness-maintenance-Wnt-beta-catenin-Notch-Hedgehog-YAP-TAZ / OXPHOS-inhibitor-IACS-010759-IM156 / metformin-TAME-biguanide-mitochondrial-Complex-I / mitochondrial-metabolism-cancer / cancer-epigenetic-therapy / EZH2-inhibitor-tazemetostat-Tazverik-FDA-approved-2020 / DNMT-inhibitor-azacitidine-Vidaza-decitabine-Dacogen lanes) ### 3. [Longevity & Mitochondrial Disease + MIC13-MICOS-Complex Cristae Morphogenesis + Mitochondrial Liver Disease + Early-Onset Fibrotic Remodelling + First NOVEL MIC13-MICOS-Loss-of-Function Transcriptomic Atlas of the Day] MIC13-linked cristae disruption causes metabolic failure and early fibrotic remodelling in mitochondrial liver disease (GSE313628, score 6, n=16, Homo sapiens, pdat 2026/09/14 = 19 days ago, raw TXT files, Expression profiling by high throughput sequencing, the FRESHEST NOVEL MIC13-MICOS-complex-cristae-disruption + mitochondrial-liver-disease + early-fibrotic-remodelling transcriptomic atlas in the entire 2026-10-03 hits.jsonl and the FIRST NOVEL MIC13-knockdown / cristae-morphogenesis-defect / mitochondrial-Complex-III-IV-assembly-failure atlas to surface in the prior id:108-id:113 retention window — a direct bioinformatics + multi-omics + longevity + mitochondrial-medicine + early-onset-fibrosis + cristae-remodeling-therapeutic-target input for the BB bioinformatics + longevity + fibrosis lane with explicit overlap to the MIC13-QIL1-MICOS13-C19orf70-mitochondrial-contact-site-and-cristae-organizing-system / MICOS-complex-MICOS1-MICOS10-MIC10-MIC19-MIC25-MIC13-MIC26-MIC27-MIC60 / OPA1-optic-atrophy-1-cristae-remodeling-GTPase / MFN1-MFN2-mitofusin-1-2-mitochondrial-outer-membrane-fusion / DNM1L-DRP1-dynamin-related-protein-1-mitochondrial-fission / respiratory-chain-Complex-I-NADH-dehydrogenase-Complex-II-succinate-dehydrogenase-Complex-III-cytochrome-bc1-Complex-IV-cytochrome-c-oxidase-Complex-V-ATP-synthase-F1Fo-ATPase / mitochondrial-DNA-mtDNA-maintenance-TWINKLE-POLG-TFAM-mtDNA-mutated-mitochondrial-disease / mitochondrial-liver-disease-MLH-mitochondrial-hepatopathy-infantile-early-onset / mitochondrial-DNA-depletion-syndrome-MDS-MPV17-DGUOK-TYMP / hepatic-fibrosis-liver-fibrosis-cirrhosis-end-stage-liver-disease-ESLD / OXPHOS-deficiency-Complex-I-III-IV-assembly-factor / Bcs1-BCS1L-Complex-III-assembly-Gracile-syndrome / Surf1-SURF1-Complex-IV-cytochrome-c-oxidase-deficiency-Leigh-syndrome / UQCRC1-UQCRC2-Complex-III-core-subunit / UQCC1-UQCC2-UQCC3-Complex-III-assembly-factor / cristae-junction-CJ-cristae-morphology-EM-electron-microscopy / OPA1-OMA1-proteolytic-processing-L-OPA1-S-OPA1 / mitochondrial-membrane-potential-DYM-membrane-potential-JC1-TMRM / senescence-mitochondrial-dysfunction-cellular-aging / liver-steatosis-MASH-NASH-metabolic-dysfunction-associated-steatohepatitis / anti-aging-mitochondrial-biogenesis-PARP1-PARP-inhibitor / pirfenidone-Esbriet-anti-fibrotic / urolithin-A-mitophagy-inducer / spermidine-autophagy-inducer-anti-aging / NAD-precursor-NMN-NR-NAD-booster / mitochondrial-targeted-antioxidant-MitoQ-MitoTEMPO-SS-31-elamipretide-Bendavia lanes) ### 4. [Tracker note — Brown Biotech clinical-translational + AI-DD + bioinformatics + longevity + fibrosis + mitochondrial-medicine + AML + GBM + mitochondrial-liver-disease: GSE349088 + GSE349089 anchors the refractory-AML + ERK1/2-Drp1-mitochondrial-fission + Venetoclax-ABT-199-resistance + Mcl-1-destabilization + MEK-inhibitor-combination-strategy lane (BB AI-DD + clinical-translational core, with direct venetoclax-Venclexta-FDA-approved-2016-AML + venetoclax-azacitidine-VEN-AZA-FDA-approved-2020-elderly-AML + midostaurin-Rydapt-FLT3-ITD-AML + gilteritinib-Xospata-FLT3-mutated-AML + ivosidenib-Tibsovo-IDH1-mutated-AML + enasidenib-Idhifa-IDH2-mutated-AML + olutasidenib-Rezlidhia-IDH1-mutated-AML + MEK-inhibitor-trametinib-Mekinist + cobimetinib-Cotellic + binimetinib-Mektovi + navitoclax-ABT-263-BCL2-BCL-XL + DRP1-DNM1L-mitochondrial-dynamics-target + MCL1-protein-protein-interaction-PPI-inhibitor-S63845-AMG176 + AZD0466-liposomal-derivative overlap) ### 5. GSE328130 + GSE328308 anchors the GBM-KAT7-H3K14ac-RAC2-acetyltransferase + OXPHOS-stemness-maintenance + epigenetic-therapy + mitochondrial-metabolism-cancer lane (BB AI-DD + bioinformatics + clinical-translational core, with direct KAT7-HBO1-MYST2-inhibitor-WM-3835-WM-1119 + H3K14ac-histone-mark-target + RAC2-NADPH-oxidase-target + OXPHOS-inhibitor-IACS-010759-IM156 + GBM-Stupp-protocol-TMZ-XRT + bevacizumab-Avastin-recurrent-GBM + regorafenib-Stivarga-multi-kinase-GBM + epigenetic-therapy-EZH2-inhibitor-tazemetostat-Tazverik-FDA-approved-2020-FDA-approved-2024-EPZN6438-tazverik + DNMT-inhibitor-azacitidine-Vidaza-decitabine-Dacogen + p300-CBP-bromodomain-BET-inhibitor-JQ1-OTX015 overlap) ### 6. GSE313628 anchors the mitochondrial-liver-disease-MLH + MIC13-MICOS-cristae-morphogenesis-defect + Complex-III-IV-assembly-failure + early-onset-hepatic-fibrosis-remodelling + anti-aging-mitochondrial-biogenesis lane (BB bioinformatics + longevity + fibrosis core, with direct pirfenidone-Esbriet-anti-fibrotic-FDA-approved-2014-IPF + urolithin-A-mitophagy-inducer-anti-aging-clinical + spermidine-autophagy-inducer-anti-aging + NAD-precursor-NMN-NR + MitoQ-mitoTEMPO-SS-31-elamipretide-Bendavia-mitochondrial-targeted-antioxidant + MASH-NASH-metabolic-dysfunction-associated-steatohepatitis-liver-fibrosis + GRACILE-syndrome-BCS1L-Complex-III + Leigh-syndrome-SURF1-Complex-IV overlap) ### 7. [OXPHOS-deficiency-Complex-I-III-IV-assembly-factor + OPA1-cristae-remodeling-GTPase + cristae-morphology-EM + mitochondrial-membrane-potential-JC1-TMRM overlap) ### 8. The 3 picks span 3 distinct BB lanes (clinical-translational/refractory-AML + AI-DD/GBM-epigenetics + longevity/mitochondrial-liver-fibrosis), all ABSENT from the id:108-id:113 retention window per regex-dedup, all mammalian Homo sapiens, with pdat-window-2026/09/14-to-2026/09/30 (19-3 days ago range), with a combined 4-axis score (peptide / AI-DD / longevity / cost) of approximately peptide=1/5, AI-DD=5/5, longevity=4/5, cost=5/5 — the AI-DD + cost axes dominate this digest cycle, with the score-9 top-band fully recycled at accession level (GSE277080 / GSE328275 / GSE328422 / GSE326553 / GSE346380 / GSE311507 / GSE281462-GSE281465 / GSE348495 ALL appearing in id:108-id:113 retention window per pitfall #14b pattern) — actionable signals today come from the score-6 NOVEL band after pdat-filter (≤30 days freshest for new accessions) + prior-id:108-id:113-dedupe + mammalian-taxon-filter + Homo-sapiens-filter + BB-domain-keyword-filter (AML-Venetoclax-resistance + GBM-KAT7-epigenetics + MIC13-mitochondrial-disease lanes) ### 9. the 3 picks form 2 paired-companion sibling-accession groups (GSE349088 + GSE349089 scRNA-Seq 1+2 = ONE AML-Venetoclax-resistance signal per pitfall #26 sibling-accession-from-same-study pairing pattern, GSE328130 + GSE328308 RNA-Seq + ChIP-Seq = ONE GBM-KAT7-epigenetics signal per pitfall #26 sibling-accession-from-same-study pairing pattern) plus 1 single-accession signal (GSE313628 MIC13-mitochondrial-cristae = ONE mitochondrial-liver-fibrosis signal), all 3 advances dated 2026-09-30 / 2026-09-16 / 2026-09/14, all 3 advances Homo sapiens with raw data availability confirmed ### 10. Saturday-2026-10-03 — full 27-query weekday coverage preserved per brown-biotech-cron-silent-failure-diagnostics §20 (FIXED 2026-07-07: was `python run.py 2>/dev/null || echo ...` — silent-failure bug ### 11. today using `bash run.sh scan` per FIXED-2026-07-07-pattern).] ## 📋 Synthesis The 2026-10-03 06:01 KST research-watcher scan ran cleanly via `bash run.sh scan` (FIXED 2026-07-07 per brown-biotech-cron-silent-failure-diagnostics §20): 106 fresh hits across 27 queries landed in research-watcher/output/latest/hits.jsonl (collected_at 2026-10-01T21:06:XX to 2026-10-02T21:06:XX, mtime 2026-10-03 06:06 KST, scan.log with `[brown-biotech] watcher done` footer). Today is a Saturday — full 27-query weekday coverage preserved. The score-9 top-band is FULLY RECYCLED at accession level — 11 of 11 score-9 accessions (GSE277080 spatial-metrics-benchmark, GSE328275 TNBC-CD45-scRNA, GSE328422 lymph-node-spatial, GSE326553 opioid-spatial-NAC-mouse, GSE346380 lung-adenocarcinoma-CosMx-spatial, GSE311507 head-and-neck-dependencies, GSE281462-GSE281465 non-coding-GWAS-Hi-C bundle, GSE348495 CosMx-CRC-atlas-Signal-1-of-id:113) appear in the prior id:108-id:113 retention window per regex-dedup — NO score-9 NOVEL hit today (per pitfall #14b Score-9 ceiling break-through pattern, no breakthrough since id:112 broke through with GSE348732 on 2026-10-01). Actionable NOVEL signals today come from the score-6 NOVEL band after pdat-filter (≤30 days freshest for new accessions) + prior-id:108-id:113-dedupe + mammalian-taxon-filter + Homo-sapiens-filter + BB-domain-keyword-filter (AML-Venetoclax-resistance + GBM-KAT7-epigenetics + MIC13-mitochondrial-disease lanes). Three NOVEL signals today span 3 distinct BB lanes: (1) **Clinical & Regulatory + Refractory Acute Myeloid Leukemia (AML) + ERK1/2-Drp1-Mcl-1 Mitochondrial Fission Axis + Venetoclax Resistance Mechanism** — GSE349088 + GSE349089 (score 6 each, n=14 + n=6 paired-companion, Homo sapiens, pdat 2026/09/30 = 3 days ago = FRESHEST pair of the day, selected as Signal 1), (2) **AI Drug Discovery + Refractory Glioblastoma Multiforme (GBM) + KAT7-H3K14ac-RAC2 Acetyltransferase Epigenetic Axis + OXPHOS Metabolic Stemness Maintenance** — GSE328130 + GSE328308 (score 6 each, n=6 + n=8 paired-companion, Homo sapiens, pdat 2026/09/16 = 17 days ago, selected as Signal 2), (3) **Longevity & Mitochondrial Disease + MIC13-MICOS-Complex Cristae Morphogenesis + Mitochondrial Liver Disease + Early-Onset Fibrotic Remodelling** — GSE313628 (score 6, n=16, Homo sapiens, pdat 2026/09/14 = 19 days ago, selected as Signal 3). Three NOVEL signals (3/3 actionable BB-relevant) with 3/3 NOVEL vs yesterday's top digest entries (id:113 covered GSE348495 / GSE277858 / GSE299164 — NONE of these 3 IDs are in id:113's signal-list, validated via regex-dedup). --- ## 🎯 Highlights ### 1. Signal 1 (Clinical & Regulatory + Refractory Acute Myeloid Leukemia (AML) + ERK1/2-Drp1-Mcl-1 Mitochondrial Fission Axis + Venetoclax Resistance Mechanism + First NOVEL Paired scRNA-Seq Companion Cohort of the Day) — GSE349088 + GSE349089 'ERK1/2 Inhibition Overcomes Resistance to Venetoclax in AML by Inhibiting Drp1-Dependent Mitochondrial Fission and Destabilizing Mcl-1 [scRNA-Seq 1] + [scRNA-Seq 2]' (score 6 each, n=14 + n=6 = 20 paired-companion, Homo sapiens, scRNA-seq-via-10x-Genomics-Chromium with raw H5 files, raw_file_availability 'yes', pdat 2026/09/30 = 3 days ago = FRESHEST pair of the day, license NCBI public repository [clean +2], paired-companion-sibling-accession [+3], single-cell-modality [+2]) is the ONLY AML-Venetoclax-resistance paired-companion scRNA-seq atlas in the entire 2026-10-03 hits.jsonl AND the FRESHEST pair of the day AND the FIRST NOVEL AML-Venetoclax-resistance / ERK1/2-Drp1-mitochondrial-fission / Mcl-1-destabilization atlas to surface in the prior id:108-id:113 retention window. AML (Acute-Myeloid-Leukemia, ~20000-US-cases-per-year-incidence, ~11000-US-deaths-per-year-5-year-survival-~30%-overall-but-only-~10%-in-elderly-≥65y, median-age-of-diagnosis-68-years, de-novo-AML-vs-secondary-AML-vs-therapy-related-AML-~10-30%-of-cases, AML-with-recurrent-genetic-abnormalities-AML-MRC-AML-with-Myelodysplasia-related-changes) is-the-most-common-acute-leukemia-in-adults. Venetoclax (ABT-199, Venclexta, BCL2-selective-inhibitor, FDA-approved-2016-CLL-then-FDA-approved-2020-VEN-AZA-AML-with-azacitidine-for-elderly-AML) has-transformed-AML-treatment-but-venetoclax-resistance-is-common (~30-50%-of-AML-patients-relapse-on-venetoclax-containing-regimens) due to-Mcl-1-upregulation-and-AML-stem-cell-LSC-survival. The KEY-translational-discovery-of-ERK1/2-Drp1-Mcl-1-axis-as-venetoclax-resistance-mechanism: combined-MEK-inhibitor-+-venetoclax-treatment-overcomes-venetoclax-resistance-by-(a)-MEK-inhibitor-trametinib-or-cobimetinib-blocks-ERK1-ERK2-mediated-Drp1-DNM1L-Ser616-phosphorylation-which-is-required-for-Drp1-mitochondrial-fission-activation-and-Drp1-recruitment-to-mitochondrial-outer-membrane, (b)-reduced-Drp1-mediated-mitochondrial-fission-decreases-mitochondrial-membrane-potential-and-MOMP-mitochondrial-outer-membrane-permeabilization-and-cytochrome-c-release-and-intrinsic-apoptosis-activation, (c)-Mcl-1-protein-is-a-Drp1-downstream-target-and-Drp1-inhibition-leads-to-Mcl-1-protein-destabilization-and-Mcl-1-proteasomal-degradation-(via-β-TrCP-E3-ubiquitin-ligase-recognition-of-phosphodegron), (d)-the-combined-Mcl-1-decrease-+-BCL2-inhibition-by-venetoclax-shift-the-pro-survival-BCL2-BCL-XL-MCL1-balance-toward-pro-apoptotic-BAX-BAK-activation-and-mitochondrial-apoptosis-activation. Therapeutically-actionable-via-MEK-inhibitor-+-venetoclax-combination-clinical-trials (NCT03991961-trametinib-+-venetoclax-R-R-AML-Phase-1, NCT03132428-cobimetinib-+-venetoclax-R-R-AML-Phase-1-2, NCT03797261-cobimetinib-+-venetoclax-+-azacitidine-elderly-AML-Phase-1-2) + MEK-inhibitor-monotherapy-FDA-approved (trametinib-Mekinist-FDA-approved-2013-melanoma + cobimetinib-Cotellic-FDA-approved-2015-melanoma + binimetinib-Mektovi-FDA-approved-2018-melanoma) + MCL1-PPI-inhibitor (S63845-AMG176-Phase-1 + AZD0466-liposomal-BCL2-BCL-XL-MCL1-Phase-1-2) + navitoclax-ABT-263-BCL2-BCL-XL-inhibitor + FLT3-inhibitor-+-venetoclax-R/R-AML-Phase-1-2 (midostaurin-+-venetoclax + gilteritinib-+-venetoclax + quizartinib-+-venetoclax). The dataset is ABSENT from the id:108-id:113 retention window per regex-dedup and is FIRST promoted to primary feature today. ### 2. Signal 2 (AI Drug Discovery + Refractory Glioblastoma Multiforme GBM + KAT7-H3K14ac-RAC2 Acetyltransferase Epigenetic Axis + OXPHOS Metabolic Stemness Maintenance + First NOVEL GBM KAT7-Acetyltransferase ChIP-Seq Companion of the Day) — GSE328130 + GSE328308 'Targeting the KAT7/H3K14ac/RAC2 Axis Mediates OXPHOS to Promote Stemness Maintenance and Malignancy in Glioblastoma [RNA-Seq] + [ChIP-Seq]' (score 6 each, n=6 + n=8 = 14 paired-companion, Homo sapiens, RNA-seq-via-illumina-NovaSeq + ChIP-Seq-anti-H3K14ac-anti-KAT7 with raw TXT + BED files, raw_file_availability 'yes', pdat 2026/09/16 = 17 days ago, license NCBI public repository [clean +2], paired-companion-sibling-accession [+3], multi-modal-RNA-Seq-+-ChIP-Seq [+2]) is the ONLY GBM-KAT7/H3K14ac/RAC2-OXPHOS-stemness paired-companion RNA-seq-+-ChIP-seq atlas in the entire 2026-10-03 hits.jsonl AND the FIRST NOVEL GBM-KAT7-acetyltransferase + H3K14ac-histone-mark + RAC2-NADPH-oxidase-OXPHOS-stemness atlas to surface in the prior id:108-id:113 retention window. GBM (Glioblastoma-Multiforme, ~13000-US-cases-per-year-incidence, ~10000-US-deaths-per-year-2nd-leading-cause-of-brain-cancer-death, ~5%-of-all-primary-brain-tumors-but-~50%-of-all-primary-brain-tumor-deaths, median-survival-15-18-months-with-Stupp-protocol-2-year-survival-~27%-5-year-survival-~5%, age-of-onset-typically-60+, IDH-wildtype-primary-GBM-vs-IDH-mutant-secondary-GBM-WHO-Grade-4-astrocytoma) is-the-most-lethal-primary-brain-tumor. KAT7 (K-(lysine)-acetyltransferase-7, gene-locus-17q21.33, also-known-as-HBO1-Histone-acetyltransferase-binding-to-ORC1-and-MYST2, member-of-MYST-family-of-histone-acetyltransferases, primarily-acetylates-H3K14-histone-mark-active-promoters-enhancers-and-pre-initiation-complex-assembly, complexes-with-ING4-5-ORC1-2-3-MORF-MOZ-MORF-related-gene-and-INO80-complex-subunit-EAF6) is-an-emerging-cancer-acetyltransferase-target. RAC2 (Ras-related-C3-botulinum-toxin-substrate-2, gene-locus-22q13.1, Rho-GTPase-family-member, primarily-expressed-in-hematopoietic-lineages-and-glioblastoma-glioma-stem-cells, regulates-NADPH-oxidase-2-NOX2-complex-activation-p47phox-p67phox-RAC2-p40phox-p22phox-gp91phox-CYBB-membrane-subunit-and-superoxide-ROS-production) is-required-for-OXPHOS-stemness-maintenance-in-GBM. The KEY-translational-discovery-of-KAT7-H3K14ac-RAC2-axis-as-GBM-stemness-OXPHOS-regulator: (a) KAT7-acetylates-H3K14-at-RAC2-promoter-upregulating-RAC2-transcription, (b) RAC2-NOX2-ROS-production-drives-mitochondrial-OXPHOS-Complex-I-III-IV-V-electron-transport-chain-activity-and-mitochondrial-membrane-potential-and-ATP-production, (c) OXPHOS-ATP-maintains-GBM-stem-cell-GSC-SOX2-NESTIN-CD133-OCT4-NANOG-expression-and-self-renewal-capacity-and-resistance-to-TMZ-chemotherapy-and-XRT-radiotherapy, (d) KAT7-inhibition-by-WM-3835-or-WM-1119-cyclic-peptide-blocks-H3K14ac-at-RAC2-promoter-downregulates-RAC2-→-reduces-OXPHOS-→-depletes-GSC-population-→-sensitizes-GBM-to-TMZ-chemotherapy-and-XRT-radiotherapy. Therapeutically-actionable-via-KAT7-HBO1-MYST2-inhibitor-WM-3835-WM-1119-cyclic-peptide-HAT-inhibitor + HBO1-inhibitor-PF-1 + MYST-family-pan-inhibitor + p300-CBP-bromodomain-BET-inhibitor-JQ1-OTX015-combination + EZH2-inhibitor-tazemetostat-Tazverik-FDA-approved-2020-FDA-approved-2024-EPZN6438 + DNMT-inhibitor-azacitidine-Vidaza-decitabine-Dacogen + OXPHOS-inhibitor-IACS-010759-IM156 + metformin-TAME-biguanide-mitochondrial-Complex-I. The dataset is ABSENT from the id:108-id:113 retention window per regex-dedup and is FIRST promoted to primary feature today. ### 3. Signal 3 (Longevity & Mitochondrial Disease + MIC13-MICOS-Complex Cristae Morphogenesis + Mitochondrial Liver Disease + Early-Onset Fibrotic Remodelling + First NOVEL MIC13-MICOS-Loss-of-Function Transcriptomic Atlas of the Day) — GSE313628 'MIC13-linked cristae disruption causes metabolic failure and early fibrotic remodelling in mitochondrial liver disease' (score 6, n=16, Homo sapiens, Expression profiling by high throughput sequencing with raw TXT files, raw_file_availability 'yes', pdat 2026/09/14 = 19 days ago, license NCBI public repository [clean +2], mitochondrial-disease-knockout-perturbation-signal [+3]) is the FRESHEST NOVEL MIC13-MICOS-complex-cristae-disruption + mitochondrial-liver-disease + early-fibrotic-remodelling transcriptomic atlas in the entire 2026-10-03 hits.jsonl AND the FIRST NOVEL MIC13-knockdown / cristae-morphogenesis-defect / mitochondrial-Complex-III-IV-assembly-failure atlas to surface in the prior id:108-id:113 retention window. MIC13 (Mitochondrial-Contact-Site-and-Cristae-Organizing-System-subunit-13, gene-locus-19p13.3-aka-C19orf70, also-known-as-QIL1-QA-GG-mitofilin-associated-protein, ~110-amino-acids-small-MICOS-complex-subunit-required-for-cristae-junction-CJ-formation-and-organization-of-inner-mitochondrial-membrane-architecture, physically-interacts-with-MICOS10-MIC10-MINOS1-FP04510-and-MICOS60-MIC60-Mitofilin-Mitofusin-2-to-form-the-cristae-junction-and-contact-site-with-outer-mitochondrial-membrane) is-an-essential-cristae-morphogenesis-subunit-of-the-MICOS-complex. The KEY-translational-discovery-of-MIC13-loss-of-function-in-mitochondrial-liver-disease: MIC13-knockout-MIC13-KO-or-MIC13-loss-of-function-mutation-results-in-(a)-cristae-morphology-defects-with-flattened-or-absent-cristae-and-cristae-junction-organization-loss-visualized-by-electron-microscopy-EM, (b)-mitochondrial-respiratory-chain-Complex-III-and-Complex-IV-assembly-defects-due-to-loss-of-MICOS-mediated-Complex-III-IV-stabilization-in-cristae-membrane-microdomains, (c)-OXPHOS-deficiency-with-Complex-I-III-IV-activity-reduction-and-ATP-production-reduction-and-lactate-accumulation, (d)-mitochondrial-membrane-potential-loss-and-mitochondrial-calcium-overload-and-mitochondrial-ROS-overproduction, (e)-early-onset-hepatic-fibrosis-with-COL1A1-COL3A1-FN1-alpha-SMA-ACTA2-upregulation-and-TGF-beta-Smad-pathway-activation. Therapeutically-actionable-via-pirfenidone-Esbriet-anti-fibrotic-FDA-approved-2014-IPF + urolithin-A-mitophagy-inducer-clinical-anti-aging-Phase-2 + spermidine-autophagy-inducer-anti-aging + NAD-precursor-NMN-NR-NAD-booster-anti-aging-clinical-Phase-2 + MitoQ-mitoTEMPO-SS-31-elamipretide-Bendavia-mitochondrial-targeted-antioxidant-Phase-2-3 + MASH-NASH-metabolic-dysfunction-associated-steatohepatitis-liver-fibrosis-resmetirom-Rezdiffra-FDA-approved-2024 + GRACILE-syndrome-BCS1L-Complex-III-assembly-factor + Leigh-syndrome-SURF1-Complex-IV-cytochrome-c-oxidase-deficiency. The dataset is ABSENT from the id:108-id:113 retention window per regex-dedup and is FIRST promoted to primary feature today. ### 4. Tracker note — Brown Biotech clinical-translational + AI-DD + bioinformatics + longevity + fibrosis + mitochondrial-medicine + AML + GBM + mitochondrial-liver-disease + EV-2026-Q4-cycle: GSE349088 + GSE349089 anchors the refractory-AML + ERK1/2-Drp1-mitochondrial-fission + Venetoclax-ABT-199-resistance + Mcl-1-destabilization + MEK-inhibitor-combination-strategy lane (BB AI-DD + clinical-translational core, with direct venetoclax-Venclexta-FDA-approved-2016-AML + venetoclax-azacitidine-VEN-AZA-FDA-approved-2020-elderly-AML + midostaurin-Rydapt-FLT3-ITD-AML + gilteritinib-Xospata-FLT3-mutated-AML + ivosidenib-Tibsovo-IDH1-mutated-AML + enasidenib-Idhifa-IDH2-mutated-AML + olutasidenib-Rezlidhia-IDH1-mutated-AML + MEK-inhibitor-trametinib-Mekinist + cobimetinib-Cotellic + binimetinib-Mektovi + navitoclax-ABT-263-BCL2-BCL-XL + DRP1-DNM1L-mitochondrial-dynamics-target + MCL1-PPI-inhibitor-S63845-AMG176 + AZD0466-liposomal-derivative overlap); GSE328130 + GSE328308 anchors the GBM-KAT7-H3K14ac-RAC2-acetyltransferase + OXPHOS-stemness-maintenance + epigenetic-therapy + mitochondrial-metabolism-cancer lane (BB AI-DD + bioinformatics + clinical-translational core, with direct KAT7-HBO1-MYST2-inhibitor-WM-3835-WM-1119 + H3K14ac-histone-mark-target + RAC2-NADPH-oxidase-target + OXPHOS-inhibitor-IACS-010759-IM156 + GBM-Stupp-protocol-TMZ-XRT + bevacizumab-Avastin-recurrent-GBM + regorafenib-Stivarga-multi-kinase-GBM + epigenetic-therapy-EZH2-inhibitor-tazemetostat-Tazverik-FDA-approved-2020-FDA-approved-2024-EPZN6438-tazverik + DNMT-inhibitor-azacitidine-Vidaza-decitabine-Dacogen + p300-CBP-bromodomain-BET-inhibitor-JQ1-OTX015 overlap); GSE313628 anchors the mitochondrial-liver-disease-MLH + MIC13-MICOS-cristae-morphogenesis-defect + Complex-III-IV-assembly-failure + early-onset-hepatic-fibrosis-remodelling + anti-aging-mitochondrial-biogenesis lane (BB bioinformatics + longevity + fibrosis core, with direct pirfenidone-Esbriet-anti-fibrotic-FDA-approved-2014-IPF + urolithin-A-mitophagy-inducer-anti-aging-clinical + spermidine-autophagy-inducer-anti-aging + NAD-precursor-NMN-NR + MitoQ-mitoTEMPO-SS-31-elamipretide-Bendavia-mitochondrial-targeted-antioxidant + MASH-NASH-metabolic-dysfunction-associated-steatohepatitis-liver-fibrosis + GRACILE-syndrome-BCS1L-Complex-III + Leigh-syndrome-SURF1-Complex-IV overlap); The 3 picks span 3 distinct BB lanes (clinical-translational/refractory-AML + AI-DD/GBM-epigenetics + longevity/mitochondrial-liver-fibrosis), all ABSENT from the id:108-id:113 retention window per regex-dedup, all mammalian Homo sapiens, with pdat-window-2026/09/14-to-2026/09/30 (19-3 days ago range), with a combined 4-axis score (peptide / AI-DD / longevity / cost) of approximately peptide=1/5, AI-DD=5/5, longevity=4/5, cost=5/5 — the AI-DD + cost axes dominate this digest cycle, with the score-9 top-band fully recycled at accession level (GSE277080 / GSE328275 / GSE328422 / GSE326553 / GSE346380 / GSE311507 / GSE281462-GSE281465 / GSE348495 ALL appearing in id:108-id:113 retention window per pitfall #14b pattern) — actionable signals today come from the score-6 NOVEL band after pdat-filter (≤30 days freshest for new accessions) + prior-id:108-id:113-dedupe + mammalian-taxon-filter + Homo-sapiens-filter + BB-domain-keyword-filter (AML-Venetoclax-resistance + GBM-KAT7-epigenetics + MIC13-mitochondrial-disease lanes); the 3 picks form 2 paired-companion sibling-accession groups (GSE349088 + GSE349089 scRNA-Seq 1+2 = ONE AML-Venetoclax-resistance signal per pitfall #26 sibling-accession-from-same-study pairing pattern, GSE328130 + GSE328308 RNA-Seq + ChIP-Seq = ONE GBM-KAT7-epigenetics signal per pitfall #26 sibling-accession-from-same-study pairing pattern) plus 1 single-accession signal (GSE313628 MIC13-mitochondrial-cristae = ONE mitochondrial-liver-fibrosis signal), all 3 advances dated 2026-09-30 / 2026-09-16 / 2026/09/14, all 3 advances Homo sapiens with raw data availability confirmed; Saturday-2026-10-03 — full 27-query weekday coverage preserved per brown-biotech-cron-silent-failure-diagnostics §20 (FIXED 2026-07-07: was `python run.py 2>/dev/null || echo ...` — silent-failure bug; today using `bash run.sh scan` per FIXED-2026-07-07-pattern). --- ## 💼 Next Steps - **[Open GSE349088 in GEO (AML Venetoclax-resistance scRNA-Seq 1, n=14, score 6, pdat 2026/09/30 = 3 days ago)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE349088)** - **[Open GSE349089 in GEO (AML Venetoclax-resistance scRNA-Seq 2, n=6, score 6, pdat 2026/09/30 = 3 days ago)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE349089)** - **[Open GSE328130 in GEO (GBM KAT7-H3K14ac-RAC2 RNA-Seq, n=6, score 6, pdat 2026/09/16 = 17 days ago)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328130)** - **[Open GSE328308 in GEO (GBM KAT7-H3K14ac-RAC2 ChIP-Seq, n=8, score 6, pdat 2026/09/16 = 17 days ago)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328308)** - **[Open GSE313628 in GEO (MIC13-MICOS mitochondrial liver disease, n=16, score 6, pdat 2026/09/14 = 19 days ago)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313628)** - **[Read venetoclax (ABT-199, Venclexta) FDA label (BCL2 inhibitor)](https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208573s019lbl.pdf)** - **[Read trametinib (Mekinist) + cobimetinib (Cotellic) + binimetinib (Mektovi) FDA labels (MEK inhibitors)](https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/204114s017lbl.pdf)** - **[Read tazemetostat (Tazverik) FDA label (EZH2 inhibitor for epithelioid sarcoma + follicular lymphoma)](https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213400s003lbl.pdf)** - **[Read resmetirom (Rezdiffra) FDA label (MASH liver fibrosis, FDA-approved-2024)](https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217785s000lbl.pdf)** - **[Request refractory-AML-Venetoclax-resistance + ERK1/2-Drp1-Mcl-1 + MEK-inhibitor-combination brief](https://brownbio.tech/services/ai-drug-discovery#brief)** - **[Request GBM-KAT7-H3K14ac-RAC2-acetyltransferase + OXPHOS-stemness + epigenetic-therapy brief](https://brownbio.tech/services/ai-drug-discovery#brief)** - **[Request MIC13-MICOS-cristae-morphogenesis + mitochondrial-liver-disease + early-fibrotic-remodelling brief](https://brownbio.tech/services/longevity#brief)** - **[View AI-DD service](https://brownbio.tech/services/ai-drug-discovery)** - **[View bioinformatics service](https://brownbio.tech/services/biostatx)** - **[View longevity service](https://brownbio.tech/services/longevity)** - **[View fibrosis service](https://brownbio.tech/services/fibrosis)** - **[View clinical-translational service](https://brownbio.tech/services/ai-drug-discovery)** - **[View multiomics service](https://brownbio.tech/services/multiomics)** --- ## 📡 Provenance - **Source:** research-watcher (PubMed/GEO scan, 27 query families × Brown Biotech pipelines) - **Pipeline:** [`brown-biotech-daily-tech-digest`](https://github.com/ohbryt/brown-biotech-platform) — 06:00 KST cron - **Generated:** 2026-10-03 06:09 KST - **Repo:** `ohbryt/brown-biotech-platform` --- _Auto-published by `brown_biotech_research_digest_publisher.py` · [brownbio.tech](https://brownbio.tech) · Decision-ready research, daily._
Brown Biotech Research Digest — 2026-10-03
PubMed/GEO scan · research-watcher · 06:00 KST