Table 1.
Retrieved differentially expressed genes in CF (adapted from [31]).
The lower part of the table shows genes shared between two or more studies when all six studies are combined. Common genes in at least three studies are underlined.
Fig 1.
Common genes in CF, PI and Liver Disease were retrieved from OMIM, CTD and HuGE. Candidate genes were also retrieved from published works (PubMed) and datasets were re-analyzed in GEO. Potential modifier genes from the 3 different origins were compared and analyzed to search for pathways and protein-protein interactions.
Fig 2.
Venn diagrams of the OMIM search.
42 different genes were found to be common in CF and CF associated genes (left). 46 genes were shared by PI and Liver Disease (right).
Fig 3.
Venn diagrams showing the common genes in CF, CF associated genes and Liver Disease (OMIM).
24 genes were found in common in CF, CF associated genes and Liver Disease.
Fig 4.
Venn diagrams of the CTD database search.
The 3 shared genes in CF, Pancreatic diseases and Liver Disease were TGFB1, TNFRSF1A and CFM1.
Fig 5.
Venn diagrams of the HuGE Navigator database search.
Common genes in PI, CF and Liver Disease were CFTR, SPINK1, GSTP1, PRSS1, ADRB2, GSTM1, GSTT1, HRAS, MIF, OGG1 and TNF. (score > 5).
Table 2.
Retrieved differentially expressed genes in Liver Disease (from [38–41]).
When possible, names or abbreviations as well as OMIM accession number were added (in italic). The number sign # is used because α1-antitrypsin deficiency is caused by mutation in the SERPINA1 gene (OMIM: 107400). “?” is used when no result was obtained in our OMIM search for the corresponding gene name or when several results could be retrieved. The lower list is retrieved from [21] shows the Solute Carrier Family (SLC, sodium/potassium/chloride transporter family) with differential gene expression in NASH.
Table 3.
Retrieved differentially expressed genes in Chronic Pancreatitis (from [43]).
Some genes were withdrawn according to the reasons explained in Methods.
Table 4.
Combined differentially expressed genes in Chronic Pancreatitis [43, 44].
Some genes were withdrawn according to the reasons explained in Methods. OMIM ID and full names were searched for each gene. 23 genes were found to be decreased and 229 genes were found to be increased in Chronic Pancreatitis (p<0.05).
Table 5.
List of the genes retrieved from SE40445, GSE48452 and GSE44314.
Genes that were found in at least two groups are underlined.
Table 6.
Genes involved in CF, Chronic Pancreatitis and Liver Disease.
Common genes present in our re-analyzed data of the GEO database and in our bibliographic analysis. Common genes in CF and in pancreatic and in liver affections are underlined.
Fig 6.
Gene-pathway association of the new potential modifier genes in KEGG and REACTOME.
The 3 common genes in CF, which were retrieved from Table 6, were submitted to the pathway search, using VennViewer in CTD. 1, 1 and 9 pathways were retrieved for IFI16, IGFBP2 and CCNE2, respectively. No pathway was common between those genes.
Table 7.
Associated pathways with the retrieved potential modifiers in CF, in CF and Chronic Pancreatitis and in CF and Liver Disease.
Common pathways are underlined.
Table 8.
Associated diseases with the retrieved potential modifiers in CF, in CF and Chronic Pancreatitis and in CF and Liver Disease.
The list of genes was submitted to CTD search and associated diseases were retrieved. In bold: diseases which may present relevant involvement in CF physiopathology.
Fig 7.
PPI networks association of the new potential modifier genes.
The recent 10.0 version of STRING (High confidence ≥ 0.7) was used to search for PPI. A. PPI between proteins encoded by IFI16, CCNE2 and IGFBP2 (CF candidates). We observed that CFTR and IFI16 have a common partner: UBC. B. Interactions involving the proteins encoded by common genes in CF and Chronic Pancreatitis (EPHX1, HLA-DQA1 -DQB1, DSP and CFTR). EPHX1, DSP and CFTR were found to be linked by UBC. C. Networks formed by the proteins encoded by the genes found in CF in link to Liver Disease (SLC33A1, GPNMB, NCF2, RASGRP1, LGALS3 and PTPN13). SLC33A1 forms a protein complex together with CFTR, with UBC as an intermediate. D. Network formed by the proteins encoded by the genes involved in CF, in CF plus Chronic Pancreatitis and in CF plus Liver Disease, which were found in a network linked to the CFTR protein. UBC was observed as a central node. UBC is likely a key component in CF physiopathology. The proteins used in the search tool are marked by a red arrow.
Fig 8.
Schematic representation of the results.
Candidate genes are shown in each organ. The corresponding proteins presenting PPI are linked by a red line.