Tanget al., Science 376 , eabe1505 (2022) 27 May 2022 2of13
Feature
Promoter (<=1kb)
5' UTR
1st Exon
Other Exon
1st Intron
Other Intron
Do
Distal Intergenic
Feature Distribution
MSK
organoids
WCM
organoids
Cell lines
PDX
PARCB8
PARCB6P
MSKEF1PARCB1
PDX16bPDX16a
VCaP
LNCaP
WCM155
MSKPCa18
MSKPCa16
MSKPCa15
MSKPCa11
MSKPCa8
MSKPCa1
Percentage(%)
1 2 3 4 5 6 7 8 9 10 11 12 13 141516171819202122 X
SU2C Patients
MSKPCa8
MSKPCa9
MSKPCa10
MSKPCa11
MSKPCa12
MSKPCa13
MSKPCa14MSKPCa15
MSKPCa16MSKPCa17
MSKPCa18
MSKPCa19
MSKPCa20
MSKPCa22MSKPCa24
PDX01aPDX09a
PDX16a/bPDX10a
PDX34a
MSKPCa/PDX
Sample type: Organoid Organoid only Tissue
C D
EF
A
AR
MSKPCa1MSKPCa2MSKPCa3MSKPCa8MSKPCa9MSKPCa10MSKPCa11MSKPCa12MSKPCa13MSKPCa14MSKPCa15MSKPCa16MSKPCa17
SYP
GAPDH
LNCaPVCaP22Rv1
C4-2PC3
DU145H660
WCM154WCM155WCM1078WCM1262
MSKPCa18MSKPCa19MSKPCa20MSKPCa22MSKPCa24
PDX01aPDX09aPDX10aPDX16aPDX16bPDX34a
AR
SYP
GAPDH
AR
SYP
GAPDH
ATAC-seq group
Group 1
Group 2
Group 3
Group 4
AR expression
AR high
AR low
AR neg
0 2 4 6
UMAP-1
0
2
UMAP-2
PDX34a
MSKPCa8
DU145
MSKPCa22
PDX01a
WCM154
MSKPCa20
MSKPCa14
MSKPCa10
VCaP
22Rv1
MSKPCa3
MSKEF1
MSKPCa2
PDX16bPDX16a
C4-2
MSKPCa13
MSKPCa12
MSKPCa19 LNCaP
MSKPCa18MSKPCa17
PARCB6
PDX09a
PARCB3
WCM1078
MSKPCa24
WCM155
MSKPCa15
PARCB1
PARCB8
WCM1262
MSKPCa16
PDX10a
PC3
MSKPCa1
MSKPCa11
MSKPCa9
H660
UMAP for ATAC-seq data
Pearson correlation
ATAC-seq group
Sample souce
Group 1
Group 2
Group 3
Group 4
MSK organoids
WCM organoids
Cell lines
PDX
GSE118207
ATAC-seq group
Sample source
Sample name
Sample type
Organoid
Tissue
B
Fig. 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.
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