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Investigating_3D_expansion.md

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Investigating 3D expansion

Expand a little on the main result (which is that adding genes whose proms have contacts with regions with DM CpGs improves the deconvolution performance. We could maybe have a look at which genes are added and speculate on why?

3D epigenomics - better justify in text, look at results of 3dpromet…

Genes added to BPRNACan for BPRNACanProMet

ACLY, AGGF1, AKT1, ANK1, ANKS3, AP3M2, AP5S1, ARHGAP9, ARHGDIA, ARHGEF39, ARSG, ATG4B, ATG4D, ATP2A3, BCL2L2, BEND3, BIN2, BRAT1, C11orf42, C12orf57, C16orf71, C7orf26, C7orf50, CABLES2, CALM2, CAP2, CAPG, CAPN15, CARD10, CBX2, CCDC106, CCDC107, CD320, CD4, CD82, CDC42EP4, CDK11B, CDKN2D, CDSN, CEBPE, CENPM, CGA, CIB1, CITED4, CLK4, CLPTM1, COMMD8, COPZ1, CORO1A, CRNKL1, CSNK2B, CTSD, CTSZ, CUL9, CYC1, CYTH1, DCPS, DCUN1D2, DDAH2, DDR1, DHODH, DHTKD1, DIABLO, DLX2, DNASE1L2, DNMBP, DOK3, DPCD, DTNB, DUS2, E4F1, EHMT2, ENTPD2, EPHX3, ERI1, ERI2, ESPN, ETHE1, EXOSC4, FAM160A2, FAM167B, FASN, FASTK, FOXK2, FYCO1, FZR1, GABRB1, GCGR, GGT1, GLB1L, GLS2, GMEB2, GOLGA2, GPAA1, GPANK1, GPD2, GSG1, HAND2, HELZ2, HIST1H2AL, HLA-E, HSPA9, HSPB6, ICAM3, IGFLR1, IKZF4, IL18BP, INPP5J, IQCE, ITGAE, ITPKC, KLHDC4, KLHL6, LBX2, LIN37, LMBR1L, LOXL3, LRRC32, LRTOMT, LTC4S, LY6G6C, LY6G6D, LYL1, LYNX1, LYPD2, MAB21L3, MADD, MAF1, MAFK, MAML1, MAP4K2, MAP4K4, MARS, MEN1, MEPCE, MGAT1, MGAT4B, MIB2, MIP, MLF2, MLST8, MMP23B, MTCH1, MTG1, MTHFD1, MTMR14, MUC4, MVD, MYB, MYBPC3, MYO1A, NAA40, NABP2, NACC1, NCAPD2, NCK2, NCLN, NDUFS8, NFKBIB, NKAPL, NLRP6, NOL9, NOP10, NPDC1, NPEPL1, NPFF, NPRL2, NR1H3, NR2F6, NRL, NSFL1C, NUMA1, OR52W1, OS9, OSR1, P2RX4, P4HB, PACS2, PAK2, PAOX, PAX8, PCDHGB6, PCK2, PDE6A, PDIA5, PDLIM7, PENK, PHC3, PHKG1, PHLPP2, PIEZO1, PIGX, PILRB, PLA2G15, POLL, POP7, POU4F2, PPP1CA, PPP1R27, PRKAR2A, PRLHR, PROZ, PSENEN, PSORS1C1, PTPN22, PTPN6, PUF60, RAD9A, RASSF1, RAVER1, RBM23, RBM4B, RELB, RELT, RHOF, RIPPLY3, RNF121, RNF166, ROCK2, RPN1, RTEL1, S1PR4, SAMM50, SAR1A, SCRIB, SEMA4B, SERPINF2, SERPINH1, SETD1B, SGSM3, SGTA, SHARPIN, SHROOM1, SIAH1, SIM2, SIPA1L3, SIRT2, SLC15A3, SLC16A3, SLC16A6, SLC17A9, SLC19A1, SLC25A15, SLC48A1, SLC4A2, SLC7A14, SLC7A6, SMG6, SNX21, SPATA13, SPIDR, SQSTM1, SRCAP, SRR, SSH3, SSTR5, STEAP3, STK16, SUCLG2, SULT1A3, SUOX, SYCP2L, SYNJ2, SYS1, TARBP2, TBC1D20, TBX4, TCIRG1, TEX30, TFDP1, THAP4, THOP1, TLE6, TLX1, TLX2, TMCO3, TMEM132A, TMEM14B, TMEM184A, TMEM63C, TMUB1, TMUB2, TNF, TNKS1BP1, TNNC2, TPST2, TRA2B, TRMT1, TYK2, U2AF1L4, U2AF2, UBR5, VASN, VPS18, VPS9D1, VSX1, WDR87, WIPI1, WWP2, XXYLT1, ZBTB12, ZCWPW1, ZDHHC4, ZHX2, ZMYND10, ZNF132, ZNF205, ZNF276, ZNF500, ZNF641, ZNF668, ZNF74, ZSCAN10, ZSCAN18

Genes added to BPRNACan for BPRNACan3DProMet (63)

ACLY ARHGDIA ARSG ATG4D BCL2L2 BRAT1 C12orf57 C7orf50 CAPG CBX2 CD4 CD82 CDKN2D CLK4 COPZ1 CYTH1 DCUN1D2 DNMBP ERI1 FASN FOXK2 GCGR GLS2 HELZ2 HIST1H2AL HLA-E HSPB6 ICAM3 IGFLR1 IQCE KLHL6 LBX2 LIN37 LMBR1L MAFK MIP MLF2 MTMR14 MYBPC3 NCK2 OSR1 P4HB PPP1R27 PSENEN PTPN6 RAVER1 RBM23 RPN1 SLC16A3 SLC16A6 SPATA13 SPIDR SYNJ2 TLX2 TMCO3 TMEM184A TNKS1BP1 TYK2 U2AF1L4 UBR5 WIPI1 ZNF641 ZNF668

Genes in BPRNA not in BPRNACan anymore (307)

ABCG1, ABHD14B, ABI3, ADTRP, AGAP1, AIF1, AKR1C1, AKR1C3, ALOX5, ANKH, AP1S3, APP, ARHGEF11, ARHGEF4, ARRB1, ASIC3, ATF3, ATP2B4, ATP8B4, ATRN, B3GALT2, BAALC, BACE2, BCL11A, BEND7, BIVM, BMP6, BTBD19, BTNL9, C19orf48, C20orf27, C2orf88, CACNA1E, CADM4, CAMK1, CAMK2D, CAMKK1, CASS4, CCL20, CCL3, CCL3L1, CCR1, CCR9, CD101, CD248, CD300A, CD302, CD4, CD82, CD83, CD93, CHI3L2, CHRFAM7A, CLEC4E, COL13A1, COL4A3, COX6C, CPNE7, CRISPLD2, CRKL, CRTAP, CST3, CXCL2, CXCR5, CYBRD1, DBN1, DCAF12, DMXL2, DNAAF1, DNAH14, DOCK9, DPH1, DPH6, DPPA4, DSTN, ECHDC3, EFNA5, EGR1, EGR2, ELOVL6, ERBB2, EREG, ESAM, EVA1B, EVI5, FAM114A1, FAM171A1, FAR2, FCER1G, FCGR2A, FCGR3A, FCRLA, FEZ1, FGD6, FHL3, FNIP2, FRMPD3, FUT8, G0S2, GAL3ST4, GAS7, GCM1, GCNT2, GFPT2, GIMAP4, GINS2, GIPR, GNA12, GNA15, GNB5, GPR183, GPR82, GREM2, H1F0, HAAO, HAVCR1, HCK, HENMT1, HES1, HES4, HIST1H1T, HK3, HLA-DRA, HLA-DRB5, HMGB3, HMOX1, HS3ST3A1, ICAM1, ICOS, IFIT3, IGF2BP2, IGSF6, IL1R1, IMMP1L, IMMP2L, INSR, ITGAD, ITGAX, JSRP1, KALRN, KBTBD11, KCNK5, KDM1A, KIAA0408, KIAA1257, KIF21A, KLF4, KLHL3, KRT72, LAIR2, LDLR, LGALS3, LILRA4, LIPE, LMTK3, LRRC23, LRRC56, LTA4H, MAGEH1, MAML2, MAP3K7CL, MBLAC2, MCCC2, MCM5, MMAA, MMP28, MNDA, MPZL2, MRPL28, MRPS9, MRVI1, MYL9, MYO1B, MYO1C, MYO1E, N6AMT1, NAGA, NBEA, NBL1, NBPF14, NDC80, NDUFAF1, NEIL3, NLRP3, NOD2, NOG, NPDC1, NRGN, NSUN7, NT5DC3, OASL, OBSCN, OPLAH, OR13A1, ORM1, PALD1, PAOX, PARP15, PDCD1, PDE4D, PDE6H, PEBP1, PF4V1, PFKFB2, PFKM, PHPT1, PILRA, PKIG, PLAUR, PLCG2, PLEKHA7, PLXND1, PODN, PPFIBP1, PPT1, PRDM10, PRDM5, PRSS35, PSMG1, PTCH1, PTGDR2, PTGES, PXMP4, RAB27B, RAB30, RANBP17, RBM11, RGS18, RILP, RIMKLB, RNASE4, RP9, RPS6KL1, RRP1B, S100A8, SASH1, SDC3, SECTM1, SEMA4A, SERPINB2, SERPING1, SETBP1, SETD7, SH2B2, SH3BGRL2, SLC16A1, SLC16A5, SLC19A1, SLC22A23, SLC26A8, SLC35G2, SMARCAD1, SORBS2, SOX13, SOX5, SPATA18, SPHK1, SPN, SPON2, SPRY2, STARD9, STYK1, SUSD3, SVIL, SYN3, SYTL3, TBC1D8, TBXAS1, TCL1B, TCTN2, TGM3, THBS1, TIAM2, TIMM13, TIMP1, TM6SF1, TMEM171, TMOD2, TNFRSF10A, TNFRSF10D, TNFRSF18, TOP1MT, TRAPPC6A, TRIM58, TRMT1, TRPC1, TRPM6, TSPAN13, TSR1, TST, TTC21A, UPB1, WNT3, ZBTB32, ZBTB46, ZC2HC1A, ZDHHC1, ZG16B, ZMYM5, ZMYND19, ZNF287, ZNF385A, ZNF519, ZNF608, ZNF781, ZNHIT6, ZSCAN29

Genes lost in BPRNACan from BPRNA but restored in BPRNACan3DProMet (2)

CD4 and CD82

CD82 is highly expressed in Macrophages meanwhile CD4 is predictive to CD4 Tcells but highly expressed in cancer cells too.

Gene B cancer CD4 CD8 M0 M1 M2 Mono Neu NK
CD82 84.3326385930249 64.5127166749311 18.9039662777569 23.8211997177599 102.211008948327 258.391212325986 220.407036029912 29.4471317199325 101.043018616383 0.455706678016801
CD4 0.330954816228237 22.4139343320294 11.0265972708576 0 3.15251007047522 1.01637602768557 0 5.042559199645 0.675410302863387 0

Based on the paper DNA Methylation in T-Cell Development and Differentiation, CD4 expression responsible for Tcell differentiation is regulated by DNA methylation.
Tcells differentiation going from Double Negative (CD4- ; CD8-) into DP (CD4+ ; CD8+) and for CD4TCells SP (CD4+ ; CD8-). In CD8+Tcells, CD4 downregulation due to DNMTs and CD4 enhanced expression in CD4+Tcells due to TETs.


To do

  1. Genes connection is cell type specific

  2. Associate cpgs to cell type

  3. Make a function that chose a cell type and find the connected genes

  4. Find that the majority of genes connected to macrophages are differentially expressed for macrophages.

  5. Pray

  6. Cell type specific cpgs are located in hubs

  7. Make network pchic and cpgs cell type specific

  8. Look at macrophages

  9. Make a pchic network of BPRNACan genes + Newly added Genes in another color

  10. Do GO analysis on genes/cell types

  11. Find some cluster of CpGs in IGV

  12. Pray that one of the result is relevant and say hallelujah!

  13. Make a cell specific network

  14. Add genes specific from 3D

  15. Add sig cpgs specific


I. Gene connection is cell type specific I hope

1. Associate cpgs to cell type

Number of CpGs associated with each cell type

B cancer CD4 CD8 M0 M1 M2 Mono Neu NK normal wb Total
954 1312 1301 1293 990 984 941 1038 969 1219 187 112 1896

2. Association Genes with cell type using cpgs connections

B cells

Genes with sigCpGs in promoter and connected to sigCpGs in enhancer through cell type specific chromatin contact

CD4 PRMT5-AS1 RBM23 ARSG SLC16A6 CBX2 SLA2 FAM78A

Cancer cells

Genes with sigCpGs in promoter and connected to sigCpGs in enhancer through cell type specific chromatin contact

RNU7-163P, CD82, RP11-58K22.4, RP11-58K22.5, MYBPC3, AC090559.2, SPI1, TNKS1BP1, ADRBK1, ANKRD13D, ETS1, CD4, C12orf57, PTPN6, U47924.31, RP11-370I10.6, ZNF641, LMBR1L, GLT1D1, SPATA13-AS1, SPATA13, PRMT5-AS1, RBM23, BCL2L2, BCL2L2-PABPN1, AC135050.5, ZNF668, ACLY, TTC25, ARSG, SLC16A6, WIPI1, CYTH1, CBX2, AC174470.1, FAM195B, GCGR, PPP1R27, ARHGDIA, P4HB, RP11-498C9.3, CCDC57, FASN, TEX19, SLC14A1, CDKN2D, FAM129C, AC008397.1, LRRC25, AC002398.11, AC002398.9, AD000671.6, IGFLR1, LIN37, PSENEN, U2AF1L4, AC002398.12, C19orf55, HSPB6, OSR1, AC005041.17, LBX2-AS1, LBX2, RP11-523H20.3, TLX2, NCK2, AC009505.2, SLA2, HELZ2, RP11-188P20.3, SNRK-AS1, KLHL6, CTD-3080P12.3, CTC-436P18.1, SMIM15, CLK4, HIST1H2AL, HIST1H2BPS2, HCG14, HLA-E, AC073957.15, C7orf50, AC093734.1, MAFK, TMEM184A, BRAT1, IQCE, CEBPD, SPIDR, PVT1, FAM78A

CD4 Tcells

Genes with sigCpGs in promoter and connected to sigCpGs in enhancer through cell type specific chromatin contact

TNKS1BP1, LAG3, MLF2, PTMS, CD4, C12orf57, PTPN6, U47924.31, LMBR1L, SPATA13-AS1, SPATA13, AC108004.3, ARSG, SLC16A6, WIPI1, CCDC57, FASN, RP13-516M14.2, SLC16A3, TEX19, AC009505.2, HELZ2, KLHL6, HLA-E, AC093734.1, MAFK, TMEM184A, FAM78A

Macrophages

Genes with sigCpGs in promoter and connected to sigCpGs in enhancer through cell type specific chromatin contact

LMBR1L COPZ1 NFE2 PRMT5-AS1 RBM23 CYTH1 AC174470.1 FAM195B GCGR PPP1R27 ARHGDIA P4HB RP11-498C9.3 CCDC57 FASN SLC14A1 CAPG SH2D6 KLHL6 HCG14 BRAT1 IQCE KB-1980E6.2 UBR5 FAM78A

Link

Monocyte

Genes with sigCpGs in promoter and connected to sigCpGs in enhancer through cell type specific chromatin contact

LMBR1L, PRMT5-AS1, RBM23, CCDC57, FASN, CLK4, BRAT1, IQCE

40 newly added genes

ACLY, ARHGDIA, ARSG, ATG4D, BCL2L2, C7orf50, CBX2, CDKN2D, COPZ1, CYTH1, DCUN1D2, DNMBP, ERI1, FASN, GCGR, GLS2, HELZ2, HIST1H2AL, HLA-E, IQCE, LBX2, LIN37, MAFK, MIP, MLF2, MYBPC3, P4HB, PSENEN, RAVER1, RPN1, SLC16A6, SPIDR, SYNJ2, TLX2, TMCO3, TMEM184A, TNKS1BP1, UBR5, ZNF641, ZNF668