title: Molecular Mechanisms of Mild and Severe Pneumonia: Insights from RNA Sequencing.
abstract: BACKGROUND This study aimed to uncover the molecular mechanisms underlying mild and severe pneumonia by use of mRNA sequencing (RNA-seq). MATERIAL AND METHODS RNA was extracted from the peripheral blood of patients with mild pneumonia, severe pneumonia, and healthy controls. Sequencing was performed on the HiSeq4000 platform. After filtering, clean reads were mapped to the human reference genome hg19. Differentially expressed genes (DEGs) were identified between the control group and the mild or severe group. A transcription factor-gene network was constructed for each group. Biological process (BP) terms enriched by DEGs in the network were analyzed and these genes were also mapped to the Connectivity map to search for small-molecule drugs. RESULTS A total of 199 and 560 DEGs were identified from the mild group and severe group, respectively. A transcription factor-gene network consisting of 215 nodes and another network consisting of 451 nodes were constructed in the mild group and severe group, respectively, and 54 DEGs (e.g., S100A9 and S100A12) were found to be common, with consistent differential expression changes in the 2 groups. Genes in the transcription factor-gene network for the mild group were mainly enriched in 13 BP terms, especially defense and inflammatory response (e.g., S100A8) and spermatogenesis, while the top BP terms enriched by genes in the severe group include response to oxidative stress (CCL5), wound healing, and regulation of cell differentiation (CCL5), and of the cellular protein metabolic process. CONCLUSIONS S100A9 and S100A12 may have a role in the pathogenesis of pneumonia: S100A9 and CXCL1 may contribute solely in mild pneumonia, and CCL5 and CXCL11 may contribute in severe pneumonia.
authors.affiliation: Department of Emergency, General Hospital of The People's Liberation Army (PLA), Beijing, China (mainland).|Department of Hematology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China (mainland).
authors.forename: Sai
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Emergency, General Hospital of The People's Liberation Army (PLA), Beijing, China (mainland).
authors.forename: Cong
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Emergency, General Hospital of The People's Liberation Army (PLA), Beijing, China (mainland).
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Electrical and Computer Engineering, Purdue University, Indianapolis, IN, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Emergency, General Hospital of The People's Liberation Army (PLA), Beijing, China (mainland).
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Emergency, General Hospital of The People's Liberation Army (PLA), Beijing, China (mainland).
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Emergency, General Hospital of The People's Liberation Army (PLA), Beijing, China (mainland).
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Emergency, General Hospital of The People's Liberation Army (PLA), Beijing, China (mainland).
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Ultrasound, General Hospital of The People's Liberation Army (PLA), Beijing, China (mainland).
authors.forename: Fa-Qin
authors.initials: FQ
authors.lastname: Lv
authors.affiliation: Department of Emergency, General Hospital of The People's Liberation Army (PLA), Beijing, China (mainland).
authors.forename: Tan-Shi
authors.initials: TS
authors.lastname: Li
mesh_terms: D000328:Adult; D040502:Calgranulin B / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000097:blood / Q000235:genetics; D054360:Chemokine CXCL1 / Q000097:blood / Q000235:genetics; D054371:Chemokine CXCL11 / Q000097:blood / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology; D011014:Pneumonia / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D000067616:S100A12 Protein / Q000097:blood / Q000235:genetics; D017423:Sequence Analysis, RNA / Q000379:methods*
chemical_list: C483024:CCL5 protein, human; C475829:CXCL1 protein, human; C515202:CXCL11 protein, human; D040502:Calgranulin B; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; D054371:Chemokine CXCL11; D012333:RNA, Messenger; D000067616:S100A12 Protein; C090441:S100A12 protein, human