Tanget al., Science 376 , eabe1505 (2022) 27 May 2022 2of13
Feature
Promoter (<=1kb)5' UTR1st Exon
Other Exon
1st Intron
Other Intron
Do
Distal IntergenicFeature DistributionMSK
organoidsWCM
organoidsCell linesPDXPARCB8
PARCB6PMSKEF1PARCB1PDX16bPDX16aVCaP
LNCaPWCM155MSKPCa18MSKPCa16
MSKPCa15MSKPCa11MSKPCa8MSKPCa1Percentage(%)1 2 3 4 5 6 7 8 9 10 11 12 13 141516171819202122 X
SU2C PatientsMSKPCa8
MSKPCa9
MSKPCa10
MSKPCa11
MSKPCa12
MSKPCa13
MSKPCa14MSKPCa15
MSKPCa16MSKPCa17
MSKPCa18
MSKPCa19
MSKPCa20
MSKPCa22MSKPCa24
PDX01aPDX09a
PDX16a/bPDX10a
PDX34aMSKPCa/PDXSample type: Organoid Organoid only TissueC DEFAARMSKPCa1MSKPCa2MSKPCa3MSKPCa8MSKPCa9MSKPCa10MSKPCa11MSKPCa12MSKPCa13MSKPCa14MSKPCa15MSKPCa16MSKPCa17SYP
GAPDHLNCaPVCaP22Rv1
C4-2PC3
DU145H660
WCM154WCM155WCM1078WCM1262MSKPCa18MSKPCa19MSKPCa20MSKPCa22MSKPCa24PDX01aPDX09aPDX10aPDX16aPDX16bPDX34aAR
SYP
GAPDHAR
SYP
GAPDHATAC-seq group
Group 1
Group 2
Group 3
Group 4AR expression
AR high
AR low
AR neg0 2 4 6
UMAP-102UMAP-2PDX34aMSKPCa8DU145MSKPCa22PDX01aWCM154MSKPCa20MSKPCa14MSKPCa10VCaP
22Rv1MSKPCa3MSKEF1MSKPCa2PDX16bPDX16aC4-2MSKPCa13MSKPCa12MSKPCa19 LNCaPMSKPCa18MSKPCa17PARCB6PDX09aPARCB3WCM1078MSKPCa24WCM155MSKPCa15PARCB1PARCB8WCM1262MSKPCa16PDX10aPC3MSKPCa1MSKPCa11MSKPCa9H660UMAP for ATAC-seq dataPearson correlationATAC-seq groupSample souceGroup 1
Group 2
Group 3
Group 4MSK organoids
WCM organoids
Cell lines
PDX
GSE118207ATAC-seq group
Sample sourceSample nameSample type
Organoid
TissueBFig. 1. Classification of metastatic prostate cancer into four molecular
subtypes from chromatin accessibility.(A) Top: Genomic aberrations
in the prostate oncogenome from the SU2C CRPC patient samples ( 10 )
and MSKPCa organoids. Bottom: Copy number landscape of the 15 patient-
derived organoid lines and 10 matching tumor tissues using MSK-IMPACT
sequencing data. Shades of red and blue represent extent of gain and loss.
(B) Number of mutations and fraction of copy number–altered genome
of the 10 organoids and their matching patient tumor tissues. (C)Feature
distribution of the mapped ATAC-seq peaks across all samples. (D) Correlation
heatmap based on the normalized number of reads of the top 1% variable
peaks across all samples. The ATAC-seq group and the sample source are
indicated for each sample. The colors of the four ATAC-seq groups are kept
consistent throughout the paper. (E) Unsupervised UMAP on the top 1%
variable accessible peaks across all samples. (F) Immunoblot showing the
expression of AR, SYP, and GAPDH (control) across the 35 organoids, PDXs,
and cell lines.RESEARCH | RESEARCH ARTICLE