Gene Regulatory Networks (GRNs)

Gene Regulatory Networks - 2012:

Description: This lecture is delivered as part of the "Advanced Molecular Genetics I: Gene Regulation" course (see details below) and will focus on computational approaches to understand gene regulatory networks in higher eukaryotes. This 2-day lecture mainly aims to give an overview of databases and servers/tools which can assist in analyzing and interpreting the gene regulatory networks.

Course Title:  Advanced Molecular Genetics I: Gene Regulation

Course Number: 26 MG 710-001

Course Director: Iain Cartwright

Lecture/Topic Title: Comparative Genomics and Gene Regulatory Networks

Presenter: Anil Jegga, Assistant Professor, Division of Biomedical Informatics, CCHMC

Date: February 23 through February 24, 2012

Time: 10:00 AM - 11:00 AM

Location: University of Cincinnati College of Medicine

Download the presentation:

• Session 1 - Feb 23, 2012: Power point OR pdf
• Session 2 - Feb 24, 2012: Power point OR pdf

Gene Regulatory Networks - 2011:

Description: This lecture is delivered as part of the "Advanced Molecular Genetics I: Gene Regulation" course (see details below) and will focus on computational approaches to understand gene regulatory networks in higher eukaryotes. This 2-day lecture mainly aims to give an overview of databases and servers/tools which can assist in analyzing and interpreting the gene regulatory networks.

Course Title:  Advanced Molecular Genetics I: Gene Regulation

Course Number: 26 MG 710-001

Course Director: Iain Cartwright

Lecture/Topic Title: Comparative Genomics and Gene Regulatory Networks

Presenter: Anil Jegga, Assistant Professor, Division of Biomedical Informatics, CCHMC

Date: February 23 through February 24, 2011

Time: 10:00 AM - 11:00 AM

Location: Room E602 MSB, University of Cincinnati College of Medicine

Gene Regulatory Networks - 2010:

Description: This lecture is delivered as part of the "Advanced Molecular Genetics I: Gene Regulation" course (see details below) and will focus on computational approaches to understand gene regulatory networks in higher eukaryotes. This 3-day lecture mainly aims to give hands on experience to the participants to databases and tools to analyze and interpret the gene regulatory networks. Topics covered include an overview of comparative genomics, gene regulatory network analysis (transcriptional and post-transcriptional) and functional enrichment analysis.

Course Title:  Advanced Molecular Genetics I: Gene Regulation

Course Number: 26 MG 710-001

Course Director: Iain Cartwright

Lecture/Topic Title: Comparative Genomics and Gene Regulatory Networks

Presenter: Anil Jegga, Assistant Professor, Division of Biomedical Informatics, CCHMC

Date: January 20 through January 22, 2010

Time: 10:00 AM - 10:50 AM

Location: Room E602 MSB, University of Cincinnati College of Medicine

Additional Exercises

1. Using the following two gene lists, identify conserved and non-conserved common binding sites within the upstream 500 bp (Hint: when downloading the promoter sequences use 500 bp)
Gene List 1:
ADORA1
AGTRAP
CD37
COL3A1
COL4A2
COL6A1
COL6A3
DCN
E2F4
FN1
LOC374395
LOXL1
LRP3
LRP5
LUM
MMP9
NUMA1
PPARBP
PPARD
PPP2R1A
PSG9
PTGDS
PTPRN
ROM1
SNN
SPARC
THBS2

Gene List 2:
APAF1
BAD
BAX
BCL2
BID
BIRC2
BNIP3L
CASP1
CASP2
CHUK
CYCS
DFFA
DFFB
FADD
FAS
MDM2
MYC
NFKB1
NFKBIA
PRF1
RELA
RIPK1
TNF
TNFRSF10B
TP53
TP73
TRAF1

2. Using each of the known regulatory sequences given below, identify:

1. What species do they belong to?
2. What genes do they belong to or what is the nearest neighboring gene(s)?
3. How conserved are these regions evolutionarily?
4. What is the cis-element composition of these regions?
5. Identify reported SNPs in these regions?

>Example-1
GAATTCTTAGGCAAATGGATGGAAATATAACTCTTAGGGAATNGGGAATTTTAATTAAAGGTAAAGGGTT
AGTGGGGAGATGGCTCAGTGGCGAAAGTGCTTGGCATGCATGATGCCTTGGGTTTGATCCCTGGGACCCA
CATAAAAAGCCAGGCATGGCAGCATATATGGATTAATCCCTGTGCTGGGAAGGTGGAGACAGGCTCTCTG
GGGCTTGCTGGCCAGCCAGTGTTTCTCTGAATCAGTGGGCTTCAGATTCAGTGAGAGACTGTCTCAAAAT
TCAGGTGGAGAGGATAAGAGAAAGCTAACTGATGTTGATCGCCGACCTGAAAATGCACACACATGAACTA
AGGGAAAGCAGTAATAAAGTGACTTGAGTGCCCGCTCTGACNACCCAGGAGAACTAACTCAGAGACAACC
TGTCAGGCCATCTGAATTTCAATCTTCAAATATGGAGGACAATTCAAAATATAGTTTATTAAAATAGGTT
TATATATATTTTGCCTGCATTTATTTATATGTGTACCATACGTGTGTCTGGTGACCATGAGTTCAGAAGT
GGGAAGGCATTGAAGCCCGAGTAACTGGAATTACATGCAGTTGAAAAGCCACCATGTGGGTAAACTGAAA
TGGGTCTTCTAAAAGAGCAATAAATATTCTTAACTGCTGAGCAATCTCCCTAGCCCGGATTCTATTTTAT
ACATGGTCTTATCTCTACATGGTTTACAAATGAATAGTTTTAATATTTAAATACCTTTATTTAACCTCAA
TTTTCCACTCAAGATGTGTCATTGGATCCAGACTTCATTTACCAATAGTGGGAAAAAAGGGTAACTAAAT
CTACGGATGAAATCATAAAATGTTGTTTGCTTGNATACCATTTATTATTTTTAAAACTGTTTTCAAATCA
TTNTTGATTTTGAAACTTGTTTTGAAAAACACTTTTAAGTTAGAAATGAGACAAAATTTTGTGAGAAATT
GTTTCCACAATATGAAAGTACTGAAAACCAGTTATGGTAGTGCTTTTCTGTAATCCCAGCCCGGGGGAGT
TGGGGCAGAACGGTCACCATGGGTTTCAGGCAAATCTGAGATACATAGTGAGATTATGTCTCAAAACCAC
CAAAAATCAGCCAAGCAACAAAACAGAAAGAACAACCTTGGGAAGTTCAAGAAACAGTAAAATCTTGTAA
CTACTAATAGGGAACCAGTGAGTGATACTTGGTAATTAGGAGATATGAAGTGGCATTTTAGGAAACATGA
ATATTGNAAACAATGAATCTAGCTTCCAAGTTCACAGTGAAACTTCTACAACAGTATTTGTAATGGCTGA
AAGTATTACCCGCCCATTCCTTTATTAAAAAGTTGAATAATACGGGAATAATGCTATTAAGACTTAGGCA
AAGTAGATTGTGGGAGAGCACTTCCACAGCATGTGTGAGGCCCTAGATTGATTCCTGTGTCATTAACAAA
ACANACAAAAAATTGAAATAAATACAGAGGGAGGGGAGAGGGAGACCATAATTACATGCAGGGATAGCTG
AAGTCCTGAGCCACAAATCGAAGGATGTTCCCCAGCATATGGAGTAGTCTTCATGTTCTCCCAGGGACAG
TCAGCACTATGTTCACCTCAGGATCATCAAGATGAGGTAAACTGTCAAGTATGATTTCAGTCATAGGGAG
GTCTGCTTGGGATCATCAGTATTATGCAATCACGATAGATAGTTTATACAGCACCAAACTGCCACTTGGG
AAATCTTGAACTCAAACAAAAGCTCAGNNATTATTACTGTCAAAAGGTACACNTTAGACAAAATTNGGTT
GGCAGTAAGAAAGATGNGTCAAAGAGGAAAAAAAACCCATCTAATTTGTATAATCAAAATAACAAATATT
TTGTCGTTGGTAACTACTTTTAAGTTTCAGCAAAGTTATATGCTATTATCTCTATTATCATTATACTTAA
AAATATTATCACTGATAATACTTAAAATGTTTCTATACAGCAATGTATTTGTAGAGACACAACTTAGAAT
CACATATACTTTCTTACTCAAAATCTTTATTTTCAACATGATTCAGAGTAAAGAATCTTTTATATATAGG
AATAAGTAGTAACATTGAAAACATTGGACCATTTTATGTTTTTCCTTTAGCTAAATAGTCAAAAAAAAAC
TTTAAAAGAGAAGACTTAGTTTTCTGGAAATATTTAAACATGCTAAAATCATGTCAGTCTGATGACTTTT
ACAGAAAATAAAAGCATGAACTTAAAATATAAACTGATGTAACGAATCCCAGAAATTCCTCAGATATCTT
GTAAGCACTGGAACAATGTATACTTATAAATGATACAACACATTATTCTATTAGCAAACATAAACTTTAC
TATCTTTAAATCAGCCCCCACCCATACTCTCAAAAGGAATGTCGTCGAGCGTCAGTGCCTGAAGTGATAC
GCTCTGACAAATCTAACAGCTCTCTCTGTGTCATTCCTAATGCACTTGTCACTCAGCATTATCCATCCTC
ATTAATGACAATGGGAAAGTTTATCTTGGGAACACGTTTTAAATCATCTACTCTTTACAATGGGACCATG
AAATCTCTTACAAAACATGAGGCGGGAACTACTCTGACAACAAAACCCCTTCCTGGCAGCTTTATTCTTA
ATTCCTGTTCAAGGAGTAATCTGTTTATTATAAAATCATACAGAACAATATATTAAACAGAATTTGAAAC
AAGAATAGCTAGTGTGATTTTCAAGCTTACAAGTATTTTTACAACATTTTTATTAAGCTGAAAACACTGT
TGAGCCTTTTTGTGTGGTTTCATGCAATCATTTTTTTTTCTATTCTACATTATATCAACCTTTGAAAAGG
GGTTTTGCTTTGCCCAATTTTAAAATAAACTAATGACCTAGCTCTTATATATATTAAAATGCAATAATTT
GCATTACCTTAAAAGCAATTACTTAGAACCAAATNTATCCTATTAAAAAGGCTGAAAAAGTGCTGAAAAC
TCAAGTTACCTAGTNTACNTTAAAATTANCT

>Example-2
CCCACCTCTCCTCTGCTCCTTTGTCGGAATCACAAAACCCTAAAGGTTGTCTCACTTGGGAAGGCAGCAG
ATAGGTACATTTCCGTAGCCCAGAAATGCCACTTTTATGGCCCTGTTTGTCTCCCTGCTCTAGGTTCTGA
ATGGGGCTGAACAAAACAGCAGTGCAGAGCTGGCTAGACGTCTGGGCTTAATTGTTTTATGGTTTAAATA
AGGTGGACACTCTTTCCTTTGAAATCGGATTATAGGAATGTTTTGTCTATGGCCCACGGAGATCAGGATC
TTTCTGGCTGAGAGGGAGAGGTGAAGAGCATTCAAGGAATGGGCTACAAACTGGGGAGTGGGGGCAGCCT
GGAACAGTCAGAGTCCTACTCTGAAGTCTTGCAGGCAGCAGCGGAAATAAACTGTGCATCAGGATAAGGG
GGCCTGGGAGTTTAGGGTACGTGCCAGGAGCAGAGGTCCTGGGAGCTTCGGATAGAGTGGTGCATCCGCG
TGCGCAAAGGGTTTTCTAGACTAGAAAAACGCCTGAGTGGAGGAGATTCTGGCCATTCCTTTGCAATGTT
TCTTTATTCCTGAAGGGAGGGTAACAAAAGAGGACAGTGTGGAACCCTTCTCAAGGTTTATTTCAAGAAT
TTAGAGAACTAAAGAACAGAGGCAACTACCTTCCGGGAATCCCTCTCCTTTGGAGCTGTTTAGAGGCTTC
TTTCTCCCAACTTGCCTTCGGCTCAGCCTGGGATCTCTGCTGGCTTTTCTCCAACCAGTTTGCATTGGAA
CAAGTGAACGCGAGGTGGCGCTGTTGCTCAATGTTAGAGGC

>Example-3
AGATCTCACCTAAGAAGGCATCATGTGACACCCCCCCCTTCTGTGGGCTCCTGGGAACCCCAGGACCCAG
CTCCAAAAGCCTCCGTTTGCATGTCCCCTAAGATTCCCTGGCTTGGACGTTGGAGCTACAAGCCCCTGCT
TCACATCCCCCCTTCGGATGTTCCAGCTGCCTTTATCTCCCTGTGGTAACAGAGCAAATATACTCAGGCC
CTGGAGCAGGGCACATGCAGGCTGTTGACTCTTGAGCAAAGTCTTCCCTCCGGAGGGCGCAGCACAGGCT
GCTGGACATGTGTGGAGAGGCCAATGGCCTCTTGCATAACCCAGGAGGCCTCCTGCCCACCCCGGGGCCT
TTTCAGGGTTAGGGGTGAGACAAATTGCAAACTCATGCCCAGTTAATTTTTTAAAGCAAGACCAACAGGC
TCAGCAATGATTAGCAGACAGGTAAGTTCATCTTAATCACACTGAGGACAGGGAGGGAGGAAGAGGCTAC
TGGAGGCCCCAGGGATGGGGCCCAGTTATCAGTTAACCACACAAATGTTTCTTTCTAAAACCGCTGGCCT
TCAGCCCCCAACACTCTCATCTTCCTCTCTGAGATTCTGTGGTCAATGAGCAAGCTAGTGGCCAACAGCC
ATTGAGTGAAGCGACATGTAGCCATCCACAGTCTGTGGGATAGAAAAGCGACAGGATCC

>Example-4
GGTACCTTTTTCCCAGCAGATAGAGCTACATCTGTTGGGTTTGTAATGTAATTTGTAATTACTGCCCTTC
ATGTGGTCCAATGCCTTGAACCATCTTTAATTAAAAGCATAATTAAGGGAAGATCTAAAGGAAGACAATT
ACCAGATGGTCTTTTTTTTTTTTTTTTTTAGAAGCGGTTCGTTGCTCGGAGGGCGCAGCCCGGTCCGCTT
CGGACTCGGCTTAAGGGCCGGAGGGGTCGGAGAGGGAGGGGGGGGGGGGTCCGAGCCAGGGCTCGGG

>Example-5
AGGCTTTAATGACGGGAGATCTTTCCGCTCATTGCCCTTTCAAATACAATTGTAGATCGAACTCAGCCTT
GTCACGTTGAGGAGCGGTGCGTCCCTAACATCCAGGACGTGCCTGTCGGCTCTCGGCGGATTGCATCCCA
TCACCCCCGGGGAATGCAGC

>Example-6
AACAATTGAGAAAGTGAAACGAAGACAAAATGTGACCCACCCTTCAAACAGTTCACACCCTGAAAAATAA
GAGCAACAAATAGATAACGTAAACTTGAAAGAGCATGGCTAGATGCAGGATATGCTGGCATGTACGTGGT
TAACTGAAAGAGTTTATGGGAAGCTCAGACAGCTGGGAACTCCTGATTAAGGAGAGGCTGAAGGGCAGAA
CAGAAGCCATGTGAACAGCTGCTAAAAGGGCTAGAAGATTTCCTCTGGATTAGGTGTCCCCAGCCCATCC
CTAATGGGCCATTTCAGCACGCATCAAGTGTTATCAAGGGGTTC

>Example-7
AGACACCAGGAGATGACCTTGGCCTCTAGCCCTGTTTCTTTTCTTGGACCCTCTCCATTCCTTCACGCTG
TTATAACTGAACTTGTAGGTCCTGCCCGTCATTTATCACTGACTTTGGCTCCCAACTTGCAGACTTCCCC
CACCCTGTTCCTTCTGTAATCCTCCCAATGACATCACTAACCACGCAGATGGTGACCTGGCTGTACTCTG
ACCTCTGAGTGGCTGGTTGTGATAGCGCATG

>Example-8
TATGAACTTGTTTACAGGGCTTCATGGCTCAGAACCTACCCAGAGAATTTTCTGTTCTACATCCCCAACC
AAGCCAAGGTGTTGGGGTTCAAATTTGAGCCCCAGCTGTTAGCCCTCTGCAAAGAAAAAAAAAAAAAAAA
AAGAACAAAGGGCCTAGATTTCCCTTCTGAGCCCCACCCTAAGATGAAGCCTCTTCTTTCAAGGGAGTGG
GGTTGGGGTGGAGGCGGATCCTGTCAGCTTTGCTCTCTCTGTGGCTGGCAGTTTCTCCAAAGGGTAACAG
GTGTCAGCTGGCTGAGCCTAGGCTGAACCCTGAGACATGCTACCTCTGTCTTCTCATGGCTGGAGGCAGC
CTTTGTAAGTCACAGAAAGTAGCTGAGGGGCTCTGGAAAAAAGACAGCCAGGGTGGAGGTAGATTGGTCC
TTCTAGTTGCAGCTTCCAAGGTGCCGCCAGGTCTGGGCGTTTCACCCCACACCAAGGAGAAGCCTTTGTA
ACCCAGCCCAGCTACCGACCCAAGCCCACCCCACAGCTATTTTGCGGGAGTTTCAGTGCTATAGCAGATG
GTTTCTGTAACGAGGTCACCACAGGGCTGCACCTGGTGCTCCACTTCCATCGTCCTCATCTCTAATACAC
TGGCCTCCTCTAGTGCTCTTTTGGCAGCCTCTCACAGTGTCCGGGCCCCTGCTTCCTTTCTCCCATTTGG
TCACCTTCCCCTCTTCTAGCTAGAAGCACAGAATATGGACAGCAAACATAGCTCCAAACAAGAACTAGGA
AT

>Example-9
GCTAGCCTTAGCATAGACGTTCCACTTTTTTCTAAGGTGGAGCTTACTTCTTTGATTTGATCTTTTGTGA
AACTTTTGGAAATTACCCATCTTCCTAAGCTTCTGCTTCTCTCAGTTTTCTGCTTGCTCATTCCACTTTT
CCAGCTGACCCTGCCCCCTACCAACATTGCTCCACAAGTACAAATTCATCCAGAGAAAATAAATTCTAAG
TTTTATAGTTGTTTGGATCGCATAGGTAGCTAAAGAGGTGGCAACCCACACATCCTTAGGCATGAGCTTG
ATTTTTTTTGATTTAGAACCTTCCCCTCTCTGTTCCTAGATTACATTACACATTCTGCAAGCATAGCACA
GAGCAATGTTCTACTTTAATTACTTTCATTTTCTTGTATCCTCACAGCCTAGAAAATAACCTGCGTTACA
GCATCCACTCAGTATCCCTTGAGCATGAGGTGACACTACTTAACATAGGGACGAGATGGTACTTTGTGTC
TCCTGCTCTGTCAGCAGGGCACTGTACTTGCTGATACCAGGGAATGTTTGTTCTTAAATACCATCATTCC
GGACGTGTTTGCCTTGGCCAGTTTTCCATGTACATGCAGAAAGAAGTTTGGACTGATCAATACAGTCCTC
TGCCTTTAAAGCAATAGGAAAAGGCCAACTTGTCTACGTTTAGTATGTGGCTGTAGAAAGGGTATAGATA
TAAAAATTAAAACTAATGAAATGGCAGTCTTACACATTTTTGGCAGCTTATTTAAAGTCTTGGTGTTAAG
TACGCTGGAGCTGTCACAGCTACCAATCAGGCATGTCTGGGAATGAGTACACGGGGACC

>Example-10
GGTACCTTTTTCCCAGCAGATCCTGCTACGTCTGTCGGGTTTGTAATGTAATTTGTAATTACTGCCCTTC
ATGTGGTCCGGTGCCTTGAACCATCTTTAATTAAAAGCATAATTAAGGGAAGATCTAAAGAAAGACAATT
ACCAGATGGTCTTTTTTTTAGAGGCGGTAGTTGCGCAGAGAGGGGCTCGGGGTCTGTCCCCGGGACCCCA
CGCCTTGGGAGGGGGCGGCGGGCCCGAACGGCGCCTGCGCACTGAGGAGGCCTTGGC

>Example-11
CAAACACTTACACCCGGTCTTCAAGGCGATCTCCAGGTTCCCACCGGAGCCTTGAGAGAAGGGCAGGGCC
CCACCCTCTTGGCTCACAATTTTCAAACTTATCACCAGGTTTGCACCCTCACAGGTTCACACACAGGCTG
AGAGATGCCCAGTACACAGCCAGAGCCGAGCCCCTTCATCTGGACACACACATGTCCACGAACTCACTTG
TGTGTGCCCAAGAAAGACTACCCTGATATACTTTCCTACAGACTAAGGCTCTACAGTTTCCTATGAACCA
ACTTGGGTCAGGGTCCCGGACTCTTCTCCTGTCCCTGTTCCCCATTTCCGTCCCATTTCCCTCCATCTGT
CTGTCTCTTTCCATTAGCCAGTCTCAGGGGGACCCAGCTTACTCCTGCCCAGCCCCCTTGAGCCATCCAT
CCGTCTGTCTGCAACTACCCTGGCAGGGAATCGTTCCCCACCTCACTGGGTCCTGTCCTTCATCTCAGCC
ACACCCACCACAGAGGACCCCTCTCCCTTCCTCAGCAGGGCCTCTCATCACTCACCCGGACCCTCACTCA
CCCCTCCCTCCTCCTCCTATCTGTTTCCCTAATCTGTCAGTCAGTCTGTCTGTACACCCATCCATCCACC
CTTCCTTCCTTCCTTCCCCGCTGGGCCCCATCTCTCTCAACAATCCCAGTGTCCCATCCATCAACCTACA
GACAGCCCTGTGCTGCCAGGTAGTCTCCTCCTGGCTGCTCATCTGTTTGTCTGTCCACCCGCCCATCCAT
CCATCTGTCTCCAAGCCCATCCATCCATCTATCCACCAGCCCATCCATCATGCAAGCCACTTGCAAGTTC
TGGTGTAGGCTTCCTCAGCAAG

3. Using the gene lists (based on published microarray data; Appendix 1 below), and the applications oPOSSUM, PScan, GenomeTrafac and ConciseScanner:

1. Find the potential common transcription factor binding site clusters that could be responsible for the co-expression.
2. Find additional genome-wide targets for the signature cis-regulatory modules identified (Hint: use the feature ConciseScanner to find genome-wide additional targets for a specific transcription factor).

4. Using gene list 1 from (1) above, obtain the mouse orthologs. For the mouse orthologs, download the promoter sequences.

5. How many of the genes in the gene lists 1 and 2 have a conserved NF-kappaB site (Hint: In oPOSSUM, use "select specific profiles" option and select "NF-kappaB")?

6. Use gene lists 2, 4 and 6 from Appendix 1 (see below) and identify the enriched TFBSs, in the up and down regulated genes.

APPENDIX 1: Co-expressed gene lists

1: Nitric Oxide. 2002 Nov;7(3):165-86.
A DNA microarray study of nitric oxide-induced genes in mouse hepatocytes: implications for hepatic heme oxygenase-1 expression in ischemia/reperfusion.
Zamora R, Vodovotz Y, Aulak KS, Kim PK, Kane JM 3rd, Alarcon L, Stuehr DJ, Billiar TR.

#NAME inos_10_dn
#DESCRIPTION Ten most-downregulated genes following iNOS induction in hepatocytes
#GENES: CD151, EIF5A, EEF2, CD81, PKM2, ACT6

#NAME inos_10_up
#DESCRIPTION Ten most-upregulated genes following iNOS induction in hepatocytes
#GENES: EED, CSRP1, PCNA, HMOX1, MCM2, CDK2, MCM6, GNB1, TUBB1

2: J Nutr. 2004 Apr;134(4):762-70.
Gene expression profiling in human preadipocytes and adipocytes by microarray analysis.
Urs S, Smith C, Campbell B, Saxton AM, Taylor J, Zhang B, Snoddy J, Jones Voy B, Moustaid-Moussa N.

#NAME adip_human_dn
#DESCRIPTION Down-regulated in primary human adipocytes, versus preadipocytes
#GENES: PPARD, CEBPA, MMP2, SNN, SPARC, COL5A1, DCN, COL3A1, LRP3, COL6A3, PSG9, ATRAP, CD37, ROM1, COL4A2, LUM, PPP2R1A, LRP5, LOX, PTPRN, OKL38, IL18BP, THBS4, FN1, THBS1, LOXL1, COL6A1, ADORA1, MMP9, PPARBP, E2F4, PTGDS, THBS2

#NAME adip_human_up
#DESCRIPTION Up-regulated in primary human adipocytes, versus preadipocytes
#GENES: PFKFB3, ABCE1, PLCD1, AGTRL1, CROC4, HSD11B2, AGT, FABP4, DGKG, PTPN21, PTPRZ1, SCD, FABP5, RXRA, SMARCB1, COL1A2, CRYAB, DGAT1, ZNF336, LRP8, CTSG, 3-PAP, APM1, DPT, CAP2, IL22R, SCAP1, USP8, LYPLA1, HPCA, STAT5B, CYB5, E2F5, ALDH6A1, MMP7, LBP, GPD1, GLUL, GPX3, INSR, FXYD1, FACL2, ALDH1A2, MGST1, MAP4K3, MASP1, ECM2, PTPRS, CEBPD, KCNH2, ATP2B2, ACOX3, SPTBN4, TNFAIP2, LIPE, VN, FABP7, UCP4, LPL, ADFP, PPAR- , E2F1, IGFBP2, CHST1, GDF8, ADORA2B, ATP8A2, ATIP1, LIPC, REQ, PLEK, APOB, TAP1, AMT, PLIN, TFCP2, RXRB

3: Science. 2000 Mar 31;287(5462):2486-92.
Mitotic misregulation and human aging.
Ly DH, Lockhart DJ, Lerner RA, Schultz PG.

#NAME middleage_dn
#DESCRIPTION Downregulated in fibroblasts from middle-age individuals, compared to young
#GENES: CCNB, PLK, FOXM1, KIF11, PTGS2, KIF2C, CENPA, CDC20, H2AFX, KIF23, HMGN2, UBE2C, CCNF, CCNA, CENPF, MYB

#NAME middleage_up
#DESCRIPTION Upregulated in fibroblasts from middle-age individuals, compared to young
#GENES: COL15A1, TNFRSF11B, SERPINB2, COL6A2, IL8, FMOD, MMP12, DPT, CST6, COMP, THBS2, PTGS1, CRYBB2, MMP10, PRSS11

4: Oncogene. 2001 Jun 21;20(28):3674-82.
Distinctive gene expression profiles associated with Hepatitis B virus x protein.
Wu CG, Salvay DM, Forgues M, Valerie K, Farnsworth J, Markin RS, Wang XW.

#NAME hbx_dn
#DESCRIPTION Downregulated by expression of Hepatitis HBx protein in hepatocytes
#GENES: CD4, GSTA4, GLG1, WT1, TGFB1, MAP3K1, IL6, APR-3, TP53, CDKN1A, GSTM5, APC, GAS6

#NAME hbx_up
#DESCRIPTION Upregulated by expression of Hepatitis HBx protein in hepatocytes
#GENES: CCNI, DAD1, GSTM4, AP4B1, CDK4, TYMS, TNFRSF6, MYC, CCND3, PDCD2, PTK9, AP4S1, IGF1R, BCL2L1, TUBG1, TUBA4, TUBG2, VCL, IFNGR1, SLC5A1, MFNG, IFNAR2, CASP4, AP4E1, CDKN3

5: Nat Rev Cancer. 2002 Jan;2(1):38-47.
Hypoxia--a key regulatory factor in tumour growth.
Harris AL.

#NAME hypoxia_review
#DESCRIPTION Genes known to be induced by hypoxia
#GENES: EDN1, PFKP, MMP13, HSF, AK3, BIK, TGM2, P4HA, TEK, CDKN1B, SLC2A3, TF, CCNG2, CD99, SAT, FTL, PFKL, BNIP3, TH, RP1, STC1, HIF2A, PDGFB, VIM, IL8, LDHA, SPP1, CA9, PTGS2, PRPS1, BHLHB2, HK1, IGFBP2, TGFB1, APEX1, TFRC, ALDOA, CCL2, CA12, IL6, SLC2A1, ANGPT2, ACAT, L1CAM, TAGLN, HMOX1, FLT1, ANXA, TGFB3, PGF, IGF2, VEGF, IGFBP1, DDIT3, FOS, LRP8, ENPEP, HK2, G22P1, NOS, ADRA, HIF1A, TGFA, ENO1, PKM2, FGF3, HDAC, CDKN1A, ITGA, BNIP3L, ADM, XRCC5, EDN2, MIF, NFKB1, SERPINE, TXN, IGFBP3, COL5A1, F3, JUN, GAPD, PLAUR, TFF3, EPO, CP, HGF, PGK1

6: Science. 1999 Aug 27;285(5432):1390-3.
Gene expression profile of aging and its retardation by caloric restriction.
Lee CK, Klopp RG, Weindruch R, Prolla TA.

#NAME aged_mouse_muscle_dn
#DESCRIPTION Downregulated in the gastrocnemius muscle of aged adult mice (30-month) vs. young adult (5-month)
#GENES: IL6ST, CALM3, SIN3A, GFER, USP4, ABCB4, COL1A2, PRKCSH, PTPRR, POLA2, PLA2G7, HNRPD, COL1A1, PPP1R2, PRSS15, CLTB, FDFT1, PMP22, PSMB8, MYH2, TST, BMP8B, ADAM28, SRPR, PSMC3, CDC2L2, PPP3CC, S100A10, RAI2, NR2F1, PHOX2A, WNT4

#NAME aged_mouse_muscle_up
#DESCRIPTION Upregulated in the gastrocnemius muscle of aged adult mice (30-month) vs. young adult (5-month)
#GENES: GDF9, ARF5, MFAP5, HSPA6, HSPB1, ETV4, TFAP2B, ISLR, GADD45A, CKMT2, USP53, ATF3, ACTR1B, PBEF1, RAB1A, DCTN1, STARD7, DDX5, TM4SF3, U2AF2, SOX17, RAB21, AP3S2, CDC42, PLAGL1, AMY2B, PRSS11, ZFP90, POU3F2, HINT1, TGFB1I1, TGIF, ARHGDIB