preliminary results 2014-02-27. zoho page ki/465555000000561005/taz-yap-and- dpagt1-knockdown.html

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Preliminary results 2014-02-27

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Page 1: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

Preliminary results

2014-02-27

Page 3: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

Microarray data analysis

• 1. QC• 2. clustering analysis• 3. identify differentially expressed genes in

each set• 4. simple enrichment analysis

Page 4: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

Microarray data analysis(cont.)

• 5. enrichment analysis (gsea approach)• 6. evaluate the connection between

microarray-derived signatures vs TCGA derived signatures

• 7. apply microarray-derived signatures to TCGA raw data

Page 5: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

Microarray data

• 1. whether we had evidence YAP1,TAZ,DPAGT1 may play a role in hnsc

Page 6: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

Microarray data

• 1. whether we had evidence YAP1,TAZ,DPAGT1 may play a role in hnsc

– 1. Gsea enrichment with head-neck-cancer genesets

Page 7: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

YAP1,DPAGT1 activated genes overlap with up-regulated genes in hnsc

activated PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP

SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP

RICKMAN_HEAD_AND_NECK_CANCER_C

TAZ 0.915 0.586 /

YAP1 0.018 0.011 /

YAP1-TAZ 0 0.001 /

DPAGT1 0.031 / 0.089

Page 8: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

YAP1 repressed genes overlap with up-regulated genes in hnsc

repressed RICKMAN_HEAD_AND_NECK_CANCER_A

RICKMAN_HEAD_AND_NECK_CANCER_C

RICKMAN_HEAD_AND_NECK_CANCER_E

TAZ 0.195 0.545 0.10

YAP1 0.188 0.196 0.003

YAP1-TAZ / 0.085 0.086

DPAGT1 / / 0.52

Page 9: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

Microarray data

• 1. whether we had evidence YAP1,TAZ,DPAGT1 may play a role in hnsc

– 1. Gsea enrichment with head-neck-cancer genesets

– 2. examine the differentially expressed genes in TCGA dataset

Page 10: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

Microarray data

• 1. whether we had evidence YAP1,TAZ,DPAGT1 may play a role in hnsc

– 1. Gsea enrichment with head-neck-cancer genesets

– 2. examine the differentially expressed genes in TCGA dataset (activated/repressed genes)

Page 11: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

YAP1,DPAGT1 activated genes overlap with up-regulated genes in hnsc

activated PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP

SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP

RICKMAN_HEAD_AND_NECK_CANCER_C

TAZ 0.915 0.586 /

YAP1 0.018 0.011 /

YAP1-TAZ 0 0.001 /

DPAGT1 0.031 / 0.089

Page 12: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

YAP1 activated genes showed higher level expression in tumors from TCGA

Page 13: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

YAP1,DPAGT1 activated genes overlap with up-regulated genes in hnsc

activated PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP

SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP

RICKMAN_HEAD_AND_NECK_CANCER_C

TAZ 0.915 0.586 /

YAP1 0.018 0.011 /

YAP1-TAZ 0 0.001 /

DPAGT1 0.031 / 0.089

Page 14: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

YAP1-TAZ1 activated genes showed higher level expression in tumors from TCGA

Page 15: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

YAP1,DPAGT1 activated genes overlap with up-regulated genes in hnsc

activated PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP

SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP

RICKMAN_HEAD_AND_NECK_CANCER_C

TAZ 0.915 0.586 /

YAP1 0.018 0.011 /

YAP1-TAZ 0 0.001 /

DPAGT1 0.031 / 0.089

Page 16: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

DPAGT1 activated genes showed higher level expression in tumors from TCGA (not very clear)

Page 17: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

Microarray data

• 1. whether we had evidence YAP1,TAZ,DPAGT1 may play a role in hnsc

– 1. Gsea enrichment with head-neck-cancer genesets

– 2. examine the differentially expressed genes in TCGA dataset (activated/repressed genes)

Page 18: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

YAP1 repressed genes overlap with up-regulated genes in hnsc

repressed RICKMAN_HEAD_AND_NECK_CANCER_A

RICKMAN_HEAD_AND_NECK_CANCER_C

RICKMAN_HEAD_AND_NECK_CANCER_E

TAZ 0.195 0.545 0.10

YAP1 0.188 0.196 0.003

YAP1-TAZ / 0.085 0.086

DPAGT1 / / 0.52

Page 19: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

YAP1YAP1-TAZ

Page 20: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

Microarray data

• 1. whether we had evidence YAP1,TAZ,DPAGT1 may play a role in hnscConclusion: YAP1 and DPAGT1 activated genes seem to be differentially expressed in hnsc

Page 21: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

Microarray data

• 1. whether we had evidence YAP1,TAZ,DPAGT1 may play a role in hnscConclusion: YAP1 and DPAGT1 regulated genes seem to be differentially expressed in hnsc

• 2. whether YAP1,TAZ, DPAGT1 are related with progression of the hnsc

Page 22: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

Microarray signatures upon tumor progression in hnsc

• 1. heatmap of TCGA data using microarray signatures did not yield clear patterns

Page 23: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

Microarray signatures upon tumor progression in hnsc

• 2. microarray signatures vs TCGA signatures

Page 24: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

YAP1,DPAGT1 activated genes overlap with up-regulated genes in hnsc

activated PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP

SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP

RICKMAN_HEAD_AND_NECK_CANCER_C

TAZ 0.915 0.586 /

YAP1 0.018 0.011 /

YAP1-TAZ 0 0.001 /

DPAGT1 0.031 / 0.089

Page 25: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

YAP1 with TCGA signatures

G1+ vs normal

Up Down

YAP1- up Yes Yes

YAP1 - down Yes /

YAP1-TAZ -up Yes /

YAP1-TAZ -down Yes /

Page 26: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

YAP activated genes does not seems to be correlated with tumor progression

G1+ vs normal G2+ vs G1 G3+ vs (G1&G2)

Up Down Up Down Up Down

YAP1- up Yes Yes / Yes / Yes

YAP1 - down Yes / Yes / Yes /

YAP1-TAZ -up Yes / / Yes / Yes

YAP1-TAZ -down Yes / Yes / Yes /

Page 27: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

YAP1,DPAGT1 activated genes overlap with up-regulated genes in hnsc

activated PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP

SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP

RICKMAN_HEAD_AND_NECK_CANCER_C

TAZ 0.915 0.586 /

YAP1 0.018 0.011 /

YAP1-TAZ 0 0.001 /

DPAGT1 0.031 / 0.089

Page 28: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

DPAGT1 with TCGA signatures

G1+ vs normal

Up Down

TAZ - up Yes /

TAZ - down Yes /

DPAGT1 -up / Yes

DPAGT1 -down Yes /

Page 29: Preliminary results 2014-02-27. Zoho page  ki/465555000000561005/TAZ-YAP-and- DPAGT1-knockdown.html

DPAGT1 activated genes does not seems to be correlated with tumor progression

G1+ vs normal G2+ vs G1 G3+ vs (G1&G2)

Up Down Up Down Up Down

TAZ - up Yes / / Yes / Yes

TAZ - down Yes / Yes / / /

DPAGT1 -up / Yes / Yes / Yes

DPAGT1 -down Yes / / Yes / Yes