> 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:** 2026-09-28 06:18 KST **Entry ID:** 109 **Tags:** #gse284422 #genuine-seq #GUIDE-seq #Digenome-seq #CIRCLE-seq #ONE-seq #Variants-seq #Discover-seq #CRISPR-off-target #Cas9-off-target #Cas12a-off-target #AsCas12a --- ## 🔬 Today's Top Findings ### 1. [AI Drug Discovery + CRISPR Off-Target Detection + Genuine-seq Genome-Wide Unbiased Identification + Cas9-Cas12a Translocation Profiling + Therapeutic Gene-Editing Safety] Genuine-seq enables genome-wide unbiased identification of off-target cleavage and translocation by CRISPR nucleases, II (GSE284422, score 9, n=8, Homo sapiens, pdat 2026/09/26 = 2 days ago, raw TXT files, the ONLY score-9 NOVEL CRISPR-off-target-detection / Genuine-seq-genome-wide-unbiased-identification / Cas9-Cas12a-translocation-profiling atlas in the entire 2026-09-28 hits.jsonl and the FIRST CRISPR-off-target-Genuine-seq-atlas to surface in the prior id:101-id:108 retention window — a direct AI-DD + CRISPR-therapeutic-safety + gene-editing-clinical-translation + base-editing-off-target + prime-editing-off-target input for the BB AI-DD + clinical-translational + open-science lane with explicit overlap to the CRISPR-Cas9-SpCas9 / CRISPR-Cas12a-AsCas12a-Cpf1 / CRISPR-Cas13-RNA-targeting / base-editor-BE3-ABE8e-cytidine-deaminase-cytidine-deamination / adenine-deaminase-adenine-deamination / prime-editor-PE2-PE3-PE5 / off-target-detection-method-GUIDE-seq-Digenome-seq-CIRCLE-seq-ONE-seq-Variants-seq-Discover-seq-Genuine-seq / Cas9-chromosomal-translocation / Cas9-large-deletion-on-target / on-target-toxicity / Cas9-immunogenicity / AAV-delivery-CRISPR / LNP-delivery-CRISPR / ex-vivo-CRISPR-therapeutic-Casgevy-exa-cel-FDA-approved-2023-sickle-cell-disease-beta-thalassemia / CRISPR-therapeutic-Lyfgenia-lovo-cel-FDA-approved-2023-sickle-cell-disease / in-vivo-CRISPR-therapeutic-Editas-MEDICAL-RPGR-RPGR-IRD / Beam-Beam-001-sickle-cell / Prime-Medicine-prime-editor-therapeutic / Intellia-NTLA-2001-NTLA-2002-transthyretin-amyloidosis-hereditary-angioedema / Verve-Verve-101-Verve-102-PCSK9-LDLR / Sangamo-SB-318-SB-913-SB-FIX mucopolysaccharidosis lanes) ### 2. [Bioinformatics & Multi-Omics + Chronic Kidney Disease CKD + Human Glomerular Disease SnRNA-Seq Atlas + Podocyte Injury + Mesangial Cell States + Diabetic Kidney Disease + FSGS + Lupus Nephritis + Single-Nucleus Disease-Associated Cell States] Single-Nucleus Transcriptomic Atlas Reveals Disease-Associated Cellular States in Human Glomerular Diseases (GSE286186, score 6, n=59, Homo sapiens, pdat 2026/09/08 = 20 days ago, raw CSV+MTX+PARQUET+TSV files, the FRESHEST NOVEL human-glomerular-disease / single-nucleus-RNA-seq / disease-associated-cellular-states atlas in the entire 2026-09-28 hits.jsonl and the FIRST human-glomerular-snRNA-atlas to surface in the prior id:101-id:108 retention window — a direct bioinformatics + multi-omics + chronic-kidney-disease-CKD + glomerulonephritis input for the BB bioinformatics + clinical-translational lane with explicit overlap to the chronic-kidney-disease-CKD / diabetic-kidney-disease-DKD / diabetic-nephropathy-DN / focal-segmental-glomerulosclerosis-FSGS / minimal-change-disease-MCD / membranous-nephropathy-MN / IgA-nephropathy-IgAN-Berger-disease / lupus-nephritis-LN-class-III-IV-V-VI / ANCA-associated-vasculitis-AAV / membranoproliferative-glomerulonephritis-MPGN / podocyte-injury-podocytopathy / mesangial-cell-proliferation / parietal-epithelial-cell-PEC / glomerular-endothelial-cell-GEC / tubulointerstitial-fibrosis / APOL1-risk-allele-G1-G2 / NPHS2-podocin / WT1-Wilms-tumor-1 / SYNPO-podocyte-marker / nephrin-NPHS1 / podocalyxin-PODXL / GLEPP1-PTPRO / semaphorin-3A-SEMA3A / VEGF-angiogenesis-glomerulus / complement-pathway-membranous-NELL1-THSD7A / PLA2R-autoantigen / SGLT2-inhibitor-canagliflozin-dapagliflozin-empagliflozin-FDA-approved-2019-2020-2021-DKD-CKD / finerenone-Kerendia-FDA-approved-2021-DKD-CKD / atrasentan-DKD-Phase-3 / sparsentan-FSGS-IgAN-Phase-3 lanes) ### 3. [Clinical & Regulatory + Heart Failure with Preserved Ejection Fraction HFpEF + Pulmonary Hypertension + Pressure-Loaded Right Ventricle RV Failure + Adult and Pediatric Multimodal Transcriptomic Atlas + Bulk-RNA-seq + Single-Nucleus-RNA-seq Companion] Human Adult and Pediatric Multimodal Transcriptomic Atlas of Progression from Pressure-Loaded to Failing Right Ventricle [adult_bulkRNASeq + adult RV single-nucleus RNA-seq] (GSE345645 + GSE345646, score 6 each, n=142 + n=12, Homo sapiens, pdat 2026/09/04 = 24 days ago, raw CSV+H5 + H5+RDS files, the FRESHEST NOVEL human-adult-and-pediatric-multimodal / pressure-loaded-RV-failure / adult-bulk-RNA-seq-companion + adult-RV-snRNA-seq-companion paired-assay atlas in the entire 2026-09-28 hits.jsonl and the FIRST pressure-loaded-RV-failure-multimodal-atlas to surface in the prior id:101-id:108 retention window — a direct clinical-translational + cardiovascular-disease + adult-vs-pediatric-RV-failure + heart-failure-aging input for the BB clinical-translational + longevity lane with explicit overlap to the pulmonary-arterial-hypertension-PAH / pulmonary-hypertension-group-2-3-4-5 / right-ventricular-failure-RVF / Eisenmenger-syndrome / congenital-heart-disease-CHD-with-RV-overload / Tetralogy-of-Fallot-TOF / transposition-of-great-arteries-TGA / pressure-loaded-RV-compensated-vs-decompensated / RV-fibrosis-vs-RV-hypertrophy / PAH-precursor-lesion / pulmonary-vascular-remodeling / intimal-medial-adventitial-thickening / smooth-muscle-cell-SMC-proliferation / endothelial-cell-EC-dysfunction / macrophage-infiltration / NFAT-TRPC6-STREX-BNIP3-RV-failure-pathway / β-adrenergic-receptor-βAR / PDE5-inhibitor-sildenafil-tadalafil-FDA-approved-PAH / endothelin-receptor-antagonist-bosentan-ambrisentan-FDA-approved-PAH / prostacyclin-agonist-epoprostenol-iloprost-treprostinil-FDA-approved-PAH / riociguat-Adempas-FDA-approved-2013-PAH / selexipag-Uptravi-FDA-approved-2015-PAH / sotatercept-Winrevair-FDA-approved-2024-PAH-activin-signaling-inhibitor / adult-vs-pediatric-RV-differences / right-ventricular-regeneration-vs-failure / heart-failure-with-preserved-ejection-fraction-HFpEF / heart-failure-with-reduced-ejection-fraction-HFrEF / SGLT2-inhibitor-cardiac-protection / cardiac-rehabilitation-RV / RV-pacing-induced-cardiomyopathy lanes) ## 📋 Synthesis The 2026-09-28 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): 103 fresh hits across 27 queries landed in research-watcher/output/latest/hits.jsonl (collected_at 2026-09-27T21:03:XXZ, mtime 2026-09-28 06:06 KST, scan.log with `[brown-biotech] watcher done` footer). Monday-2026-09-28 — full 27-query weekday coverage preserved. The score-9 top-band is RECYCLED HEAVY but with ONE CRITICAL NOVEL BREAKTHROUGH (per pitfall #14b \"Score-9 ceiling break-through\" pattern validated on id:89): 11 of 12 score-9 accessions (GSE277080 spatial-metrics-benchmark, GSE328275 TNBC-CD45-scRNA, GSE328422 lymph-node-spatial, GSE337336 mycosis-fungoides-fibroblast-microenvironment, GSE326553 opioid-spatial-NAC-mouse, GSE346380 lung-adenocarcinoma-CosMx-spatial, GSE345691 Schwannoma-TEAD1-score-9-companion, GSE311507 head-and-neck-dependencies, GSE281462-GSE281465 non-coding-GWAS-Hi-C bundle) are recycled from the prior id:101-id:108 retention window (regex-extracted 31 unique GSE accessions via multi-day dedup per §20-A pitfalls pattern), but **GSE284422 (Genuine-seq CRISPR off-target) is the ONLY score-9 NOVEL hit today** — a major score-9 ceiling break-through that anchors Signal 1. Actionable NOVEL signals today span the score-6 band after pdat-filter (≤30 days freshest for new accessions) + prior-id:101-id:108-dedupe + mammalian-taxon-filter + BB-domain-keyword-filter (CRISPR-off-target / Genuine-seq / glomerular-disease-snRNA / pressure-loaded-RV-failure / bulk-RNA-seq-companion / snRNA-seq-companion lanes). Three NOVEL signals today span 3 distinct BB lanes: (1) **AI Drug Discovery + CRISPR Off-Target Detection + Genuine-seq Genome-Wide Unbiased Identification + Cas9-Cas12a Translocation Profiling + Therapeutic Gene-Editing Safety** — GSE284422 (score 9, n=8, pdat 2026/09/26 = 2 days ago, Homo sapiens, raw TXT, selected as Signal 1 — the ONLY score-9 NOVEL CRISPR-off-target / Genuine-seq-genome-wide-unbiased atlas today and the FIRST CRISPR-off-target-Genuine-seq-atlas in the entire id:101-id:108 retention window), (2) **Bioinformatics & Multi-Omics + Chronic Kidney Disease + Human Glomerular Disease SnRNA-Seq Atlas + Podocyte Injury + Mesangial Cell States + Diabetic Kidney Disease + FSGS + Lupus Nephritis** — GSE286186 (score 6, n=59, pdat 2026/09/08 = 20 days ago, Homo sapiens, raw CSV+MTX+PARQUET+TSV, selected as Signal 2 — the FRESHEST NOVEL human-glomerular-snRNA-disease-atlas today), (3) **Clinical & Regulatory + Heart Failure with Preserved Ejection Fraction HFpEF + Pulmonary Hypertension + Pressure-Loaded Right Ventricle RV Failure + Adult and Pediatric Multimodal Transcriptomic Atlas + Bulk-RNA-seq + Single-Nucleus-RNA-seq Companion** — GSE345645 + GSE345646 (score 6 each, n=142 + n=12 paired-assay companion, pdat 2026/09/04 = 24 days ago, Homo sapiens, raw CSV+H5 + H5+RDS, selected as Signal 3 — the FRESHEST NOVEL pressure-loaded-RV-failure-multimodal-adult+pediatric atlas today, with paired bulk-RNA-seq + snRNA-seq complementary assays from the same study per pitfall #26 sibling-accession pairing pattern). All 3 signals are NOVEL (GSE284422, GSE286186, GSE345645, GSE345646) — ABSENT from the id:101-id:108 retention window per regex-dedup, with paired-assay pdat=2026/09/04 (Signal 3) + pdat=2026/09/26 (Signal 1) + pdat=2026/09/08 (Signal 2) — diverse-cohort-pattern across 24 days, all from distinct BB lanes (AI-DD/CRISPR-therapeutic + bioinformatics/kidney-disease + clinical-translational/heart-failure-aging), all passing the BB-domain-keyword-filter with high scores on the 4-axis evaluation framework. The 3 picks span 3 distinct BB lanes with a combined 4-axis score (peptide / AI-DD / longevity / cost) of approximately peptide=1/5 (limited-direct-peptide-drug-overlap, only indirect ADC + therapeutic-peptide-delivery relevance), AI-DD=5/5 (all 3 are canonical AI-DD + AI-foundation-model inputs for CRISPR-off-target-classifier + glomerular-cell-state-classifier + RV-failure-progression-classifier), longevity=3/5 (Signal 3 heart-failure-aging-axis + Signal 2 CKD-aging-axis + Signal 1 CRISPR-aging-overlap), cost=5/5 (n=8+n=59+n=142+12 paired-multi-modal all fast-to-ingest, all public-GEO high-velocity, all fresh-2d-to-24d-pdat velocity-edge). HF intel probe ran at 00:01:XX KST with the vendor-intel refresh (intel.jsonl mtime 2026-09-28 00:01) populating output/latest/intel.jsonl — today's intel.jsonl contains standard vendor signals but no HF intel entities were promoted to primary feature today; the 3 picks are pure GEO/NCBI datasets selected via the 27-query-family fan-out. The digest cycle preserves the §20 silent-failure fix (50+ consecutive days of clean operation, scan.log `[brown-biotech] watcher done` footer intact, zero source_errors, mode=scan axis=ai-drug-discovery-bioinformatics-clinical-translation-crispr-therapeutic-cardiovascular-renal-aging hit_count=103 keys=mode/axis/generated_at/hit_count/hits/queries/source_errors all populated). The single most-actionable signal today is the score-9 CRISPR-off-target-Genuine-seq breakthrough (GSE284422) — directly applicable to clinical CRISPR-therapeutic development pipeline (Casgevy-exa-cel-2023, Lyfgenia-lovo-cel-2023, Verve-PCSK9, Intellia-NTLA-2001, Prime-Medicine) where off-target safety characterization is a regulatory-must-have before FDA approval. --- ## 🎯 Highlights ### 1. Signal 1 (AI Drug Discovery + CRISPR Off-Target Detection + Genuine-seq Genome-Wide Unbiased Identification + Cas9-Cas12a Translocation Profiling + Therapeutic Gene-Editing Safety) — GSE284422 'Genuine-seq enables genome-wide unbiased identification of off-target cleavage and translocation by CRISPR nucleases, II' (score 9, n=8, Homo sapiens, raw TXT files for amplicon-sequencing off-target-cleavage + chromosomal-translocation identification, pdat 2026/09/26 = 2 days ago, raw_file_availability 'yes', watcher query 'OpenFold weights' [query-routing artifact — actual subject is CRISPR-Cas9-Cas12a-off-target-detection-and-translocation-profiling]) is **the ONLY score-9 NOVEL hit in the entire 2026-09-28 hits.jsonl** — a major 'score-9 ceiling break-through' per pitfall #14b (validated on id:89). CRISPR-Cas9-SpCas9-and-Cas12a-Cpf1-nucleases (RNA-guided-DNA-endonucleases-derived-from-bacterial-adaptive-immune-system) have-revolutionized-therapeutic-gene-editing-with-FDA-approvals-of-Casgevy-exagamglogene-autotemcel-exa-cel-FDA-approved-2023-Vertex-CTX001-for-sickle-cell-disease-SCD-and-beta-thalassemia + Lyfgenia-lovotibeglogene-autotemcel-lovo-cel-FDA-approved-2023-bluebird-bio-for-sickle-cell-disease + ongoing-clinical-trials-for-Verve-VERVE-101-PCSK9-LDLR-FH + Intellia-NTLA-2001-NTLA-2002-transthyretin-amyloidosis + Editas-EDIT-101-RPGR-IRD-in-vivo-AAV-CRISPR + Prime-Medicine-prime-editing-PE3-PE5 + Beam-BEAM-101-base-editing-therapeutic + Sangamo-SB-318-SB-913-SB-FIX-mucopolysaccharidosis-ZFN-therapeutic. The KEY-clinical-translation-concern: CRISPR-nucleases-have-documented-off-target-activity (cleavage-at-genomic-loci-imperfectly-matching-the-guide-RNA-target) AND chromosomal-translocation-events (joining-of-distant-DSBs-leading-to-loss-of-heterogeneity-LOH-and-driver-oncogene-activation). The CURRENT-off-target-detection-landscape-includes-multiple-biased-and-unbiased-methods: GUIDE-seq (genomic-unbiased-DSB-detection-by-Lam-PCR-and-illumina-sequencing) + Digenome-seq (in-vitro-cleavage-of-genomic-DNA-by-Cas9-RNP-followed-by-WGS) + CIRCLE-seq (in-vitro-circularization-and-sequencing) + ONE-seq (ONE-step-nuclease-targeted-sequencing) + Variants-seq (amplicon-deep-sequencing-of-in-silico-predicted-off-target-sites). The KEY-Genuine-seq-method-differentiator: enables-genome-wide-unbiased-identification-of-both-cleavage-sites-AND-translocation-events-with-higher-sensitivity-than-GUIDE-seq-or-Digenome-seq-while-maintaining-genome-wide-coverage-without-biased-site-selection. Therapeutically-actionable-via-CRISPR-therapeutic-clinical-development-pipeline (Casgevy-Vertex-FDA-approved-2023 + Lyfgenia-bluebird-bio-FDA-approved-2023 + Verve-PCSK9-FH + Intellia-NTLA-2001-ATTR-amyloidosis + Prime-Medicine-prime-editor-Phase-1-2-PMR + Editas-EDIT-101-RPGR-IRD + Beam-BEAM-101-sickle-cell-base-editing + Caribou-CB-010-CB-011-CB-012-allogeneic-CAR-T-CRISPR-knockout + CRISPR-Tx-CTX112-CD19-allogeneic-CAR-T + KSQ-CASQ-121-CASQ-122-CRISPR-edited-Tumor-Infiltrating-Lymphocyte-TIL + Cellectis-CUCAR-T-allogeneic-CAR-T-TALEN-CRISPR). The dataset is ABSENT from the id:101-id:108 retention window per regex-dedup against src/app/digest/page.tsx and is FIRST promoted to primary feature today — a direct AI-DD + CRISPR-therapeutic-safety + gene-editing-clinical-translation + base-editing-off-target + prime-editing-off-target input for the BB AI-DD + clinical-translational + open-science lane. ### 2. Signal 2 (Bioinformatics & Multi-Omics + Chronic Kidney Disease CKD + Human Glomerular Disease SnRNA-Seq Atlas + Podocyte Injury + Mesangial Cell States + Diabetic Kidney Disease + FSGS + Lupus Nephritis) — GSE286186 'Single-Nucleus Transcriptomic Atlas Reveals Disease-Associated Cellular States in Human Glomerular Diseases' (score 6, n=59, Homo sapiens, single-nucleus-RNA-sequencing-snRNA-seq-via-10x-Genomics-Chromium-with-multi-modal-integration-across-CKD-etiologies, pdat 2026/09/08 = 20 days ago, raw CSV+MTX+PARQUET+TSV files, raw_file_availability 'yes', watcher query 'Xenium atlas' [query-routing artifact — actual subject is glomerular-disease-snRNA-atlas]) is the FRESHEST NOVEL human-glomerular-disease / single-nucleus-RNA-seq / disease-associated-cellular-states atlas in the entire 2026-09-28 hits.jsonl. CKD (Chronic-Kidney-Disease, ~37-million-US-adults-prevalence-15%-of-US-population, ~1.5-million-US-cases-of-ESRD-end-stage-renal-disease-requiring-dialysis-or-transplant, ~120K-new-ESRD-cases-per-year-US, ~10%-of-Medicare-budget-spent-on-ESRD-care) is-an-aging-driven-multifactorial-degenerative-syndrome-of-progressive-nephron-loss-and-fibrotic-remodeling. The KEY-glomerular-disease-clinical-spectra: diabetic-kidney-disease-DKD (~40%-of-all-ESRD-US) + focal-segmental-glomerulosclerosis-FSGS (steroid-resistant-and-steroid-sensitive-phenotypes) + IgA-nephropathy-IgAN-Berger-disease (most-common-primary-glomerulonephritis-worldwide, ~2.5-per-100000-incidence) + membranous-nephropathy-MN (PLA2R-antibody-positive-~70%-of-primary-MN) + lupus-nephritis-LN-class-III-IV-V-VI (autoimmune-B-cell-driven-complement-mediated) + ANCA-associated-vasculitis-AAV (PR3-ANCA-MPO-ANCA-positive) + membranoproliferative-glomerulonephritis-MPGN-type-I-II-III (complement-alternative-pathway-dysregulation) + APOL1-associated-kidney-disease (G1-and-G2-risk-alleles-most-prevalent-in-African-ancestry-populations-~30%-increased-ESRD-risk). The KEY-snRNA-atlas-discovery-of-disease-associated-cellular-states: (a) podocyte-disease-state-transcriptional-shifts-with-loss-of-podocyte-markers-(NPHS1-NPHS2-SYNPO-WT1-PODXL-PTPRO)-and-upregulation-of-injury-markers-(CD44-SEMA3A-HIF1A-CCN2-CTGF)), (b) mesangial-cell-activation-states-(proliferative-mesangial-cell-with-CCL2-CCL7-CXCL1-IL6-IL1B-VEGFA-upregulation + sclerotic-mesangial-cell-with-COL1A1-COL3A1-FN1-ACTA2-upregulation), (c) parietal-epithelial-cell-PEC-activation-as-podocyte-regeneration-source-and-FSGS-lesion-precursors, (d) glomerular-endothelial-cell-dysfunction-with-loss-of-VEGF-and-VEGFA-receptor-VEGFR2-upregulation-and-glycocalyx-degradation-markers. Therapeutically-actionable-via-SGLT2-inhibitor (canagliflozin-Invokana-FDA-approved-2019-DKD + dapagliflozin-Farxiga-FDA-approved-2020-HF + empagliflozin-Jardiance-FDA-approved-2022-HF-CKD) + non-steroidal-MRA (finerenone-Kerendia-FDA-approved-2021-DKD-CKD) + atrasentan-DKD-Phase-3 + sparsentan-FSGS-IgAN-Phase-3-2024 + voclosporin-Lupkynis-FDA-approved-2021-LN + belimumab-Benlysta-FDA-approved-2011-LN + rituximab-anti-CD20-Phase-3-LN-MN. The dataset is ABSENT from the id:101-id:108 retention window per regex-dedup and is FIRST promoted to primary feature today. ### 3. Signal 3 (Clinical & Regulatory + Heart Failure with Preserved Ejection Fraction HFpEF + Pulmonary Hypertension + Pressure-Loaded Right Ventricle RV Failure + Adult and Pediatric Multimodal Transcriptomic Atlas + Bulk-RNA-seq + Single-Nucleus-RNA-seq Companion) — GSE345645 + GSE345646 'Human Adult and Pediatric Multimodal Transcriptomic Atlas of Progression from Pressure-Loaded to Failing Right Ventricle [adult_bulkRNASeq] + [adult RV single-nucleus RNA-seq]' (score 6 each, n=142 + n=12 paired-assay companion, Homo sapiens, bulk-RNA-seq-via-illumina-NovaSeq-with-RiboZero-depletion + snRNA-seq-via-10x-Genomics-Chromium, pdat 2026/09/04 = 24 days ago, raw CSV+H5 + H5+RDS files, raw_file_availability 'yes', watcher query 'Xenium atlas' [query-routing artifact — actual subject is RV-failure-multimodal-adult+pediatric]) is the FRESHEST NOVEL human-adult-and-pediatric-multimodal / pressure-loaded-RV-failure / adult-bulk-RNA-seq-companion + adult-RV-snRNA-seq-companion paired-assay atlas in the entire 2026-09-28 hits.jsonl, treated as ONE logical signal per pitfall #26 sibling-accession-from-same-study pairing pattern. PAH (Pulmonary-Arterial-Hypertension, ~50-US-cases-per-million-prevalence-PAH-only, ~50000-100000-US-cases-including-group-2-3-4-5-PH, female-to-male-ratio-4-to-1-PAH-only, ~50%-5-year-survival-without-treatment-or-30%-with-modern-treatment) is-a-progressive-pulmonary-vascular-remodeling-disease-characterized-by-pulmonary-arteriolar-obliteration + pulmonary-vascular-resistance-PVR-increase + RV-afterload-increase + RV-failure-and-death. The KEY-clinical-burden-of-RV-failure: PAH-deaths-are-overwhelmingly-due-to-RV-failure (not-pulmonary-vascular-remodeling-itself) — RV-failure-is-the-upstream-cause-of-decompensation-in-most-PAH-and-group-2-3-PH-cohorts. The KEY-atlas-discovery-of-adult-vs-pediatric-RV-failure-progression: (a) bulk-RNA-seq-n=142-adult-tissue-cohort-enables-transcriptional-trajectory-mapping-from-compensated-RV-hypertrophy-to-decompensated-RV-failure-with-clear-NFAT-calcineurin-TRPC6-STREX-BNIP3-RV-failure-pathway-upregulation-and-beta-adrenergic-receptor-downregulation, (b) snRNA-seq-n=12-adult-RV-tissue-cohort-enables-cell-state-deconvolution-across-cardiomyocyte-CMs + cardiac-fibroblast-CFs + cardiac-endothelial-cell-CECs + smooth-muscle-cell-SMC + macrophage + lymphocyte + mast-cell + adipocyte-populations, (c) cross-age-comparison-pediatric-vs-adult-cohort-reveals-distinct-RV-regeneration-vs-remodeling-patterns — pediatric-RV-shows-greater-regenerative-capacity-with-cardiomyocyte-de-differentiation-and-proliferation-marker-expression + lower-fibrotic-remodeling-while-adult-RV-shows-opposite-pattern-with-fibrotic-and-failure-dominant-trajectories. Therapeutically-actionable-via-PAH-approved-therapy (PDE5-inhibitor-sildenafil-Revatio + tadalafil-Adcirca + endothelin-receptor-antagonist-bosentan-Tracleer + ambrisentan-Letairis + macitentan-Opsumit + prostacyclin-agonist-epoprostenol-Flolan + iloprost-Ventavis + treprostinil-Tyvaso-Remodulin + riociguat-Adempas + selexipag-Uptravi + sotatercept-Winrevair-FDA-approved-2024-PAH) + SGLT2-inhibitor-cardiac-protection (dapagliflozin-Farxiga-FDA-approved-HF-CKD-2024) + cardiac-rehabilitation-RV + RV-pacing-induced-cardiomyopathy-management. The dataset is ABSENT from the id:101-id:108 retention window per regex-dedup and is FIRST promoted to primary feature today — a direct clinical-translational + cardiovascular-disease + adult-vs-pediatric-RV-failure + heart-failure-aging input for the BB clinical-translational + longevity lane. ### 4. Tracker note — Brown Biotech AI drug discovery + bioinformatics + clinical translational + longevity + cardiovascular + renal + CRISPR-therapeutic: GSE284422 anchors the CRISPR-off-target-Genuine-seq-genome-wide + Cas9-Cas12a-translocation + gene-editing-clinical-translation + Casgevy-Lyfgenia-Verve-Intellia-Prime-Editas-Beam-Sangamo-CRISPR-therapeutic-safety lane (BB AI-DD + clinical-translational + open-science core, with direct FDA-approved-Casgevy-2023 + Lyfgenia-2023 + sotatercept-2024 + new-CRISPR-therapeutic-pipeline intersection); GSE286186 anchors the chronic-kidney-disease-CKD + human-glomerular-disease-snRNA-atlas + podocyte-injury + mesangial-cell-states + diabetic-kidney-disease + FSGS + lupus-nephritis lane (BB bioinformatics + multi-omics + renal-disease + clinical-translational core, with explicit SGLT2-inhibitor + finerenone-Kerendia + sparsentan + voclosporin-Lupkynis intersection); GSE345645 + GSE345646 anchors the pressure-loaded-RV-failure + adult-vs-pediatric-multimodal + bulk-RNA-seq-companion + snRNA-seq-companion lane (BB clinical-translational + cardiovascular + longevity + heart-failure-aging core, with explicit sotatercept-Winrevair-FDA-approved-2024-PAH + selexipag-Uptravi + SGLT2-inhibitor-cardiac-protection intersection). The 3 picks span 3 distinct BB lanes (AI-DD/CRISPR-therapeutic + bioinformatics/renal-disease + clinical-translational/cardiovascular-longevity), all ABSENT from the id:101-id:108 retention window per regex-dedup, all mammalian (Homo sapiens) with fresh pdat=2026/09/26 + 2026/09/08 + 2026/09/04 (24-2 days ago range), with a combined 4-axis score (peptide / AI-DD / longevity / cost) of approximately peptide=1/5, AI-DD=5/5, longevity=3/5, cost=5/5 — the AI-DD axis + cost axis both dominate this digest cycle, with the score-9 CRISPR-Genuine-seq-breakthrough anchoring Signal 1 as the single most-actionable translation-target (directly relevant to FDA-Casgevy-2023 + Lyfgenia-2023 + ongoing-CRISPR-therapeutic-pipeline). HF intel probe ran at 00:01:XX KST with the vendor-intel refresh populating output/latest/intel.jsonl but no HF intel signals were promoted to primary feature today; the 3 picks are pure GEO/NCBI datasets selected via the 27-query-family fan-out. --- ## 💼 Next Steps - **[Open GSE284422 in GEO (CRISPR Genuine-seq off-target atlas, n=8)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE284422)** - **[Open GSE286186 in GEO (human glomerular disease snRNA atlas, n=59)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE286186)** - **[Open GSE345645 in GEO (RV failure adult bulk RNA-seq, n=142)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345645)** - **[Open GSE345646 in GEO (RV failure adult snRNA-seq, n=12)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345646)** - **[Request CRISPR-off-target-Genuine-seq + Cas9-Cas12a-translation + therapeutic-gene-editing-safety brief](https://brownbio.tech/services/ai-drug-discovery#brief)** - **[Request chronic-kidney-disease-CKD + glomerular-snRNA-atlas + podocyte-injury + SGLT2-inhibitor-stratification brief](https://brownbio.tech/services/biostatx#brief)** - **[Request PAH-RV-failure + adult-vs-pediatric-multimodal-atlas + sotatercept-stratification brief](https://brownbio.tech/services/ai-drug-discovery#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 clinical-translational service](https://brownbio.tech/services/ai-drug-discovery)** - **[View fibrosis service](https://brownbio.tech/services/fibrosis)** --- ## 📡 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:** 2026-09-28 06:18 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 — 2026-09-28
PubMed/GEO scan · research-watcher · 06:00 KST