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Table 5 Functional clusters among target genes or their regulatory candidates

From: Using a large-scale knowledge database on reactions and regulations to propose key upstream regulators of various sets of molecules participating in cell metabolism

Regulated targetsa

Regulatory candidatesb

Fatty acid metabolism c

Cluster 1: ACAA2, ACADL, ACADVL, ACSS2, ALDH9A1, CLU, DECR1, DGAT2, DHRS4, ECH1, ARCC1, FNTB, HADHB, HMGCS2, LSS, MBLN3, NME4, PAPSS2, PDK1, PEX11A, PNPLA2, PYCR1, RETSAT, UCP2

Cluster 1: PNPLA2, PPARA, PPARG, SERPINA3, TGFB1

Cluster 2: ACADL, ACADVL, ALDH9A1, DECR1, DHRS4, EGLN3, PYCR1, RETSAT

Cluster 2: ACAA2, ACADL, ACADVL, ECH1, HADHB, PNPLA2, PPARA, PPARD

Cholesterol metabolism

Cluster 4: ACAA2, ACSS2, DGAT2, HMGCS2

Cluster 3: ACAA2, ACSS2, DGAT2, HMGCS2, LSS, PPARD, RXRA

Cell adhesion and migration

Cluster 7: CDH11, CLU, COL18A1, DPT, LAMA2, LAMA4, PTK7, SERPINE2

Cluster 4: COL18A1, LAMA2, LAMA4, SERPINE2, TGFB1

Cell development

Cluster 3: SERPINA3, SERPINE1, SERPINE2

Cluster 6: CLU, COL18A1, DPT, EGLN3, FNTB, PPARD, PPARG, RXRA , SERPINE1, TGFB1

 

Cluster 5: EGLN3, LAMA2, LAMA4, PPARD, PPARG, RXRA, RXRG, TGFB1

 

Cluster 8: CLU, JUNB, JUND , PPARD, PPARG, TGFB1

Cell signaling

Cluster 6: APCDD1, CA6, CDH11, CLU, COL18A1, DGAT2, DPT, HTRA3, LAMA2, LAMA4, LCN2, LGALS9, NPR3, PNPLA2, OPDC3, PTK7, RETSAT, SERPINA3, SERPINE1, SERPINE2, STRA6

Cluster 7: (PPAR signaling pathway) : ARNTL, ARNTL2, CLOCK, CLU, COL18A1, DPT, GLN3, ERCC1, FNTB, HLTF, HMGCS2, JUNB, JUND, LAMA2, LAMA4, MBNL3, PAPSS2, PNPLA2, PPARA, PPARD, PPARG, RXRA, RXRG, SERPINA3, SERPINE1, TGFB1

Peroxisome microbody

Cluster 5: DHRS4, ECH1, PEX11A

 

Cluster 9: CDH11, JUND, NPR3, PAPSS2, TGFB1

  1. aTranscripts experimentally identified as responsive to PPARA agonists in cell culture[21] (see Additional file2: Table S2 for details) were clustered using the DAVID functional annotation tool[5]. Only clusters with an enrichment > 0.5 and a Benjamini score < 0.15 were kept. Eventually, a synthetic description was chosen to name the cluster.
  2. bFifty upstream regulatory candidates that were automatically-proposed according to best specificity scores (see Additional file2: Table S2 for a detailed list) were clustered. All molecules were first linked to their related genes, with heterodimer protein complexes (e.g., PPARA:RXRA) being switched in the two genes (e.g., PPARA and RXRA).
  3. cThe results show that the input list of regulated transcripts and the output list of proposed candidates notably shared clusters related to fatty acid and cholesterol metabolisms. All clusters were enriched in transcription factors, and especially in peroxisome proliferator-activated receptors (PPAR) isotypes and their partners RXR (indicated in bold face) when calculated from the list of regulatory candidates.
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BMC Systems Biology

ISSN: 1752-0509

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