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. 2021 Jul 22;8:713170. doi: 10.3389/fcvm.2021.713170

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Copyright © 2021 Liu, Wu, Xu, Saaoud, Vasilopoulos, Shao, Zhang, Wang, Shen, Yang, Lu, Sun, Drummer, Liu, Li, Hu, Yu, Praticò, Sun, Jiang, Wang and Yang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Venn diagram shows that there are several shared OCRGs in acute inflammations (AIs), metabolic diseases (MDs), autoimmune diseases (ADs), and organ failures (OFs). (A) Venn diagram shows 17 genes are shared among acute inflammatory diseases (AIs). SERPINA1 and AZU1 are shared upregulated genes; TOMM20 and ECI2 are shared downregulated genes by sepsis/ARDS, sepsis/shock, and trauma. CD24, FKBP8, and GRN are shared upregulated genes by sepsis and trauma. HSPD1, BNIP3, HSPA9, SET, DDHD2, TOMM70, KLRG1, ZNF266, AFG3L2, and CLIP4 are 10 genes that are commonly downregulated in sepsis and trauma groups. After removing five uncertain genes (upregulated in one type of disease and downregulated in another type of disease), 21 genes are upregulated and 58 genes are downregulated in AIs. (B) Venn diagram shows seven genes are shared among metabolic diseases (MDs). VAMP8 and SERPINA1 are shared upregulated genes by obese and atherosclerosis; DNM2 and MTFP1 are shared upregulated genes by type 2 diabetes (T2D) and atherosclerosis. AASS is shared a downregulated gene by three metabolic diseases, and CD24 and CYB5A are shared downregulated genes by T2D and atherosclerosis. After removal of 12 uncertain genes, 34 genes are upregulated and 34 genes are downregulated in MDs. (C) Venn diagram shows 33 genes are shared among autoimmune diseases. GPRC5A, LAMP3, and MX2 are shared upregulated genes; PPARGC1A and AASS are shared downregulated genes by rheumatoid arthritis (RA), autoimmune skin disease (ASD), and inflammatory bowel disease (IBD). Other 28 genes are common genes between two autoimmune diseases. After removal of 21 uncertain genes, 59 genes are upregulated, and 68 genes are downregulated in ADs. (D) Venn diagram shows 16 genes are shared in organ failure datasets. BAX and GRN are shared upregulated genes by hepatitis B virus-associated acute liver failure (HBV-ALF). AKAP9 is the common downregulated gene in HBV-ALF, end-stage renal failure (ESRF), and hemodialysis; NPC1, RAB7A, CLOCK, KLRG1, SEC23IP, and SNX1 are the common downregulated genes in ESRF and hemodialysis. After removal of 13 uncertain genes, 26 genes are upregulated and 99 genes are downregulated in OFs. (E) Venn diagram shows the shared and exclusive upregulated and downregulated OCRGs in these four diseases. In upregulated OCRGs, a total of 24 genes were shared by two or three different diseases. AIs and MDs shared four genes, two vesicle-related genes (RAB20 and CTSA), and two mitophagy genes (FKBP8 and ATG7). AIs and ADs shared mitophagy gene (MAP1LC3A). AIs, MDs, and OFs shared vesicle genes (GRN). MDs and OFs shared three genes autophagosome–endosome/lysosome fusion regulator (VAMP8), MT fission gene (MTFR2), and vesicle gene (POU2F2). AIs, MD, and ADs shared mitophagy (VMP1), MT fission (MX2), and vesicle (SERPINA1) genes. MDs, ADs, and OFs shared sarcoplasmic reticulum–MT gene (OSBPL8). ADs and OFs shared two mitophagy genes (ATG3 and ATG12), one MT fission gene (DCN), and three vesicle genes (CLTA, ZDHHC13, and SAMD9). MDs and ADs shared five genes including one ER–PM junctions gene (JPH3), one MT fission and fusion regulator (GDAP1), and three vesicle genes (RPTOR, ACBD5, and CCZ1). Other exclusive upregulated genes in these four diseases are listed in Supplementary Table 4A. (F) In downregulated OCRGs, a total of 67 genes were shared by two or more than two different diseases. Two MT fission genes (DDHD2 and MAPT) and two vesicle genes (AASS and CYB5A), were shared by four types of diseases (red box). ADs and OFs shared 17 OCRGs, including one ER–PM junction regulator (JPH2) and one MT contact site gene (APOOL), two MT fission regulators (DNM3 and PINK1) (also mitophagy regulator), two genes with MT fusion and mitophagy function (OMA1 and USP30), and 11 vesicle genes. AIs and OFs shared 12 OCRGs, RAB7A (ER–endosome and autophagosome–endosome/lysosome fusion), JPH3 (ER–PM junctions), VDAC1 (mitophagy, ER–MT contact, and sarcoplasmic reticulum–MT), HSPD1 (MT biogenesis), DHODH (MT fission), BNIP3 (MT fission and fusion, and mitophagy), PID1 (MT fusion), TOMM70 (MT translocation), and four vesicle genes (DNAJA3, KLRG1, SEC23IP, and STX16). MDs and OFs shared 11 OCRGs including ER–endosome genes (NPC1), ER–MT contact and ER–GC interaction regulator VAPA, ER–MT contact, ER–GC interaction and sarcoplasmic reticulum–MT regulator VAPB, two MT fission genes MYO19 and DNM1, and six vesicle genes. AIs and MDs, AIs and ADs, and MDs and ADs shared two, five, and three downregulated OCRGs, respectively. AIs, MDs, and ADs shared three downregulated OCRGs, ITPR1 (ER–MT contact, sarcoplasmic reticulum–MT), OPTN (mitophagy), and DYRK4 (vesicle gene). AIs, MDs, and OFs shared four OCRGs (EGFR, INF2, RAB30, and NOV). AIs, ADs, and OFs shared six OCRGs, VPS41 (autophagosome–endosome/lysosome fusion), two MT fission regulators DDHD1 and TMEM135, and three vesicle regulators (ECI2, CLIP4, and SNX1). Other exclusive downregulated genes in these four diseases are listed in Supplementary Table 4B. Abbreviations: AIs, acute inflammations; MDs, metabolic diseases; ADs, autoimmune diseases; OFs, organ failures; ARDS, acute respiratory distress syndrome; T2D, type 2 diabetes; HF, heart failure; HBV-ALF, hepatitis B virus-associated acute liver failure; ESRF, end-stage renal failure.