Patient organoids respond more diverse to drugs and with lower therapeutic potential than 2D cultured patient cells Patient organoids respond more diverse.

Slides:

Advertisements

Similar presentations

Cluster analysis of 50 genes identified as affecting variability and or pheromone response output Cluster analysis of 50 genes identified as affecting.

Advertisements

Statistical colorings of 1H NMR estimates of biochemical variables.

Growth rate‐dependent gene expression under glucose limitation.

Tuning the response of the DPI

Culture type shapes drug‐induced growth arrest in ovarian cancer patient cells Culture type shapes drug‐induced growth arrest in ovarian cancer patient.

Abundance of proteins matching selected subcellular locations and functions in CaCo‐2 cells. Abundance of proteins matching selected subcellular locations.

Bifurcation diagrams showing quasi‐steady‐state solutions and simulation of models. Bifurcation diagrams showing quasi‐steady‐state solutions and simulation.

Periodic changes in distribution of ERK–GFP fusion protein in cells after stimulation with EGF. (A) Confocal image of cells expressing ERK–GFP both before.

Network topology reflects target gene expression profile and function.

Hnf4g importance in human colon cancer organoids and regulation of the Hnf4a locus Hnf4g importance in human colon cancer organoids and regulation of the.

Most promoters preserve their relative activity levels across conditions. Most promoters preserve their relative activity levels across conditions. (A)

(A) Graph depicting interaction between the five regulatory motifs measured by synergy and cooccurrence. (A) Graph depicting interaction between the five.

Analysis of in silico flux changes along the exponential growth phase: (A) In silico flux changes from 24 to 36 h, from 36 to 48 h, and from 48 to 60 h.

Characterization of the inferred factor associated with the differentiation state of the cell of origin Characterization of the inferred factor associated.

Activity flow of the mTOR signaling network.

Evaluating other shRNA data and methods.

The TBON model. The TBON model. (A) Representative confocal images of E14Tg2A cells stained for Tcf3 (green), Nanog (red), Oct4 (magenta), and total β‐catenin.

Topological overlap matrix (TOM) plots of weighted, gene coexpression networks constructed from one mouse studies (A–F) and four human studies including.

Skin proliferation kinetics and in vivo fibroblast lineage tracing during dermal maturation (related to Fig 4)‏ Skin proliferation kinetics and in vivo.

Confirmation of pool data with isogenic culture

Large‐scale image‐based CRISPR‐Cas9 gene perturbation profiling

Correlating protein to mRNA and proteins per mRNA ratios

Ovarian cancer cells harbour numerous copy number alterations unlinked to drug‐induced cell death Ovarian cancer cells harbour numerous copy number alterations.

Characterization of promoters relative to pAGA1

Hierarchical structure in the yeast transcription regulatory network.

Evaluating CRISPR negative selection screens.

Genomic profiling of fitness in periodic salt stress

Heat maps showing global relative growth phenotype and comparison between measured and predicted values. Heat maps showing global relative growth phenotype.

Figure 3. Genes differentially expressed in batch cultures during adaptation to low temperature. Genes differentially expressed in batch cultures during.

RNAi causes widespread changes in cell population context leading to predictable changes in virus infection. RNAi causes widespread changes in cell population.

Alignment time for Clustal Omega (red), MAFFT (blue), MUSCLE (green) and Kalign (purple) against the number of sequences of HomFam test sets. Alignment.

Physical EGFR interactome generation and core network proteins identification. Physical EGFR interactome generation and core network proteins identification.

Validation of some ePTL candidates.

The transcript profiles in the three human cell lines based on RNA sequencing (RNA‐seq). The transcript profiles in the three human cell lines based on.

Homologous recombination deficiency scores correlate with drug‐induced cell death in primary ovarian cancer cells Homologous recombination deficiency scores.

Tfr cells’ transcriptomic profile distinguishes them from Treg and Tfh cells. Tfr cells’ transcriptomic profile distinguishes them from Treg and Tfh cells.

Effect of the loss of Kar4 on the induction of various promoters

Characterization of Factor 5 (oxidative stress response factor) in the CLL data Characterization of Factor 5 (oxidative stress response factor) in the.

The cell cycle influences circadian phase progression Circadian intervals with divisions (p1,d1,p2) last 21.95 ± 3.8 h (n = 1,926) and are significantly.

DeathPro dyes Hoechst and PI do not affect organoid growth and drug responses DeathPro dyes Hoechst and PI do not affect organoid growth and drug responses.

Drug‐induced cell death and proliferation inhibition can be quantified from serial confocal images Drug‐induced cell death and proliferation inhibition.

Notch activation in Notch1 positive feedback knock‐out intestine organoids Notch activation in Notch1 positive feedback knock‐out intestine organoids Intestine.

Antisense transcription, measurement, and correction

Two‐way unsupervised uncentered unnormalized hierarchical clustering using a Pearson's correlation of the phenotypic profiles of 4281 nonessential genes.

Transcriptomic and epigenetic changes associated with Factor 1 in the scMT data Transcriptomic and epigenetic changes associated with Factor 1 in the scMT.

Categorizing cell type‐specific auxin responses.

Development of a 3D tissue model and in vivo live imaging during dermal maturation Development of a 3D tissue model and in vivo live imaging during dermal.

Hnf4g dynamics and importance in the different cell‐type‐enriched organoids Hnf4g dynamics and importance in the different cell‐type‐enriched organoids.

Impact of growth phase on the Escherichia coli meltome and proteome

Simulation showing that the cell length variability of the entire population can mask abnormal cell length variability at a specific cell cycle period.

An integrated NHR network.

Stage‐dependent diurnal transcript changes.

Distinct collagen structures in the upper and lower neonatal dermis (related to Fig 1)‏ Distinct collagen structures in the upper and lower neonatal dermis.

Reproducibility of DeathPro drug screens

Cluster analysis of all identified models.

Antisense‐mediated regulation of SUR7.

Noise in hoxb1a/krox20 expression leads to boundary sharpening.

Characterising dermis expansion and gene expression changes during mouse development (related to Fig 1)‏ Characterising dermis expansion and gene expression.

Culture type determines effectivity of targeted drugs like SRC inhibitor dasatinib and mTOR inhibitors AZD2014 and temsirolimus Culture type determines.

Nedd4 proteins. Nedd4 proteins. (A) Schematic representation of rNedd4‐1, hNedd4‐1 and hNedd4‐2 (not to scale), with % amino‐acid identity between them.

Experimental validation of predicted endocytosis functions in human.

Drug sensitivity described by LD50 is similar in cells cultured in 2D or as organoids Drug sensitivity described by LD50 is similar in cells cultured in.

Global and focused views of human interaction map.

Dynamic regulatory map and static network for yeast response to AA starvation. Dynamic regulatory map and static network for yeast response to AA starvation.

Single‐cell RT–qPCR data

Shape‐sensitivity profiles inferred using shape projection

Intestinal differentiation is coupled with global rewiring of gene expression Intestinal differentiation is coupled with global rewiring of gene expression.

Expression profiles of 87 miRNAs expressed in SC

A, unsupervised hierarchical clustering of the expression of probe sets differentially expressed in the oral mucosa of smokers versus never smokers. A,

Two-way, unsupervised hierarchical clustering representing the 60 tumor cell lines (vertical axis) and the analyzed total, phospho- and cleaved proteins.

Presentation transcript:

Patient organoids respond more diverse to drugs and with lower therapeutic potential than 2D cultured patient cells Patient organoids respond more diverse to drugs and with lower therapeutic potential than 2D cultured patient cells Hierarchical clustering of drug response profiles determined in ovarian cancer (OC) organoids or 2D cultured patient cells of the same origin. The dashed vertical line cuts the dendrogram arbitrarily at the height of the 2D subcluster (grey).Therapeutic indices determined from LD50 values derived from OC drug screens in 2D or 3D culture. Green heat map colour indicates drug effectivity in cancer cells and low toxicity in normal cells, blue colour high toxicity in normal cells and low effectivity in cancer cells. nd, not determined, that is no fitting performed due to low response. Julia Jabs et al. Mol Syst Biol 2017;13:955 © as stated in the article, figure or figure legend