Journal: bioRxiv

Article Title: ButterflyVI: enabling high-throughput variant interpretation and biomarker discovery with functional genomics

doi: 10.64898/2026.01.20.700339

Figure Lengend Snippet: A , Summary plot of ElasticNet biomarkers of druggable genes. Each point shows a biomarker shared between CRISPR and RNAi datasets that was selected at least 5 times out of 10 ElasticNet runs, had a mean coefficient greater in absolute value than .05 and exhibit the same effect direction in both datasets. A negative weighted mean ElasticNet score indicates sensitivity, whereas a positive score indicates resistance. B–D. MDM2 ( B ) and MDM4 ( C ) dependency scores, and MDM2 mRNA expression ( D ) in cell lines classified by RPL5 status: wild type (or carrying a neutral mutation) versus carrying a functional mutation (as defined by OncoKB or ButterflyVI). E , Relative expression of RPL5 in cells transfected with control siRNA (siCtrl), GAPDH siRNA (siGAPDH), or RPL5 siRNA (siRPL5). Data are presented as the mean ± standard error of the mean (SEM). Differences between groups were evaluated using an unpaired Student’s t-test. The level of statistical significance is indicated by asterisks: ns, not significant (P > 0.05); ** P ≤ 0.01; * P ≤ 0.05. F , Cellular viability in response to DMSO (control) or Nutlin-3a treatment at varying doses in RT-4 (left) and KU-19-19 (right) models. Cellular viability is expressed as a percentage. Each point represents a single experimental data point (replicate). The colored lines indicate the mean viability for each knockdown condition (siCtrl, siGAPDH, siRPL5). The shaded bands represent the standard error of the mean (SEM).

Article Snippet: The human bladder cancer cell lines KU-19-19 and RT-4 (ACC 395 and ACC 412; DSMZ) were cultured in RPMI 1640, GlutaMAX (Gibco, 61870010) supplemented with 10% FBS (Thermo Fisher Scientific, A5256701) and 1% Penicillin-Streptomycin (Thermo Fisher Scientific, 15070063) at 37 °C in a humidified atmosphere with 5% CO2.

Techniques: Biomarker Discovery, CRISPR, Expressing, Mutagenesis, Functional Assay, Transfection, Control, Knockdown

Journal: bioRxiv

Article Title: ButterflyVI: enabling high-throughput variant interpretation and biomarker discovery with functional genomics

doi: 10.64898/2026.01.20.700339

Figure Lengend Snippet: A-B , Dose response curves to control DMSO ( A ) or Nutlin-3a ( B ) treatment on RT-4 and KU-19-19 models. Cellular viability is expressed as a percentage relative to the untreated control. Each data point represents a single experimental data point (replicate). The blue line shows the fit of the four-parameter log-logistic model. The light blue shaded band represents the 95% confidence interval for the model. The vertical red dashed line indicates the calculated IC50, and the pink shaded band represents the 95% confidence interval for the IC50 value. The specific IC50 value and its confidence interval are indicated on the graph. C , Relative expression of GAPDH in cells transfected with control siRNA (siCtrl), GAPDH siRNA (siGAPDH), or RPL5 siRNA (siRPL5). Data are presented as the mean ± standard error of the mean (SEM). Differences between groups were evaluated using an unpaired Student’s t-test. The level of statistical significance is indicated by asterisks: ns, not significant (P > 0.05); ** P ≤ 0.01; * P ≤ 0.05.

Article Snippet: The human bladder cancer cell lines KU-19-19 and RT-4 (ACC 395 and ACC 412; DSMZ) were cultured in RPMI 1640, GlutaMAX (Gibco, 61870010) supplemented with 10% FBS (Thermo Fisher Scientific, A5256701) and 1% Penicillin-Streptomycin (Thermo Fisher Scientific, 15070063) at 37 °C in a humidified atmosphere with 5% CO2.

Techniques: Control, Expressing, Transfection

Journal: Bladder Cancer

Article Title: Impact of DNA repair deficiency on sensitivity to antibody-drug conjugate (ADC) payloads in bladder cancer *

doi: 10.1177/23523735251317865

Figure Lengend Snippet: Homologous recombination (HR) deficiency confers cisplatin and PARP inhibitor sensitivity in bladder cancer cells. (a) Immunoblot showing siRNA-mediated depletion of BRCA2 protein in KU19-19 and J82 bladder cancer cell lines. Vinculin is shown as a loading control. (b) Immunofluorescence (IF) microscopy shows loss of radiation-induced Rad51 foci formation in BRCA2-depleted compared to BRCA2-intact bladder cancer cells. (c) Cell viability assays demonstrate increased sensitivity to cisplatin following BRCA2 depletion in bladder cancer cell lines. (d) Cell viability assays demonstrate increased sensitivity to PARP inhibitors olaparib and talazoparib in bladder cancer cell lines. kDa, kilodalton. NTC, non-targeting control. Gy, Gray. MFI, mean fluorescence intensity. *p < 0.01 (IC50 values). Error bars represent standard deviation of data collected from assays performed in triplicate (panel B) or quadruplicate (panels C, D).

Article Snippet: Human bladder cancer cell lines J82 and KU19-19 were purchased from ATCC and DSMZ, respectively.

Techniques: Homologous Recombination, Western Blot, Control, Immunofluorescence, Microscopy, Fluorescence, Standard Deviation

Journal: Bladder Cancer

Article Title: Impact of DNA repair deficiency on sensitivity to antibody-drug conjugate (ADC) payloads in bladder cancer *

doi: 10.1177/23523735251317865

Figure Lengend Snippet: Combined activity of MMAE and SN-38 with DNA repair inhibitors. (a) Cytotoxic activity of combining MMAE or SN-38 with ATR inhibition (berzosertib, BERZ), USP1 inhibition (ML323), or PARP inhibition (Olaparib, OLA; talazoparib, TALA) in KU19-19 (top graph) and J82 (bottom graph) bladder cancer cell lines with versus without HR deficiency conferred by BRCA2 depletion. (b) Cytotoxic activity of combining MMAE or SN-38 with ATR inhibition (berzosertib, BERZ), USP1 inhibition (ML323), or PARP inhibition (Olaparib, OLA; talazoparib, TALA) in NER-proficient ( ERCC2 WT) KU19-19 cells versus NER-deficient ( ERCC2 -mutant) KE182 cells (top graph) or NER-proficient (ERCC4 WT) H460 cells versus NER-deficient (ERCC4-deleted) H460 cells (bottom graph). Combination activity is quantified by the combination index (CI, see Methods) with positive log10(CI) values indicative of antagonism and negative log10(CI) values indicative of synergism. HRP, homologous recombination proficient (WT BRCA2); HRD, homologous recombination deficient (BRCA2 depleted); NERP, nucleotide excision repair proficient; NERD, nucleotide excision repair deficient. Error bars represent standard deviation of data collected from assays performed in quadruplicate.

Article Snippet: Human bladder cancer cell lines J82 and KU19-19 were purchased from ATCC and DSMZ, respectively.

Techniques: Activity Assay, Inhibition, Mutagenesis, Homologous Recombination, Standard Deviation