生物信息学在肺动脉高压中的研究进展

彭威, 张泽盈, 肖云彬

中国当代儿科杂志 ›› 2024, Vol. 26 ›› Issue (4) : 425-431.

PDF(532 KB)
HTML
PDF(532 KB)
HTML
中国当代儿科杂志 ›› 2024, Vol. 26 ›› Issue (4) : 425-431. DOI: 10.7499/j.issn.1008-8830.2310076
综述

生物信息学在肺动脉高压中的研究进展

  • 彭威1, 张泽盈2, 肖云彬1
作者信息 +

Research progress on bioinformatics in pulmonary arterial hypertension

  • PENG Wei, ZHANG Ze-Ying, XIAO Yun-Bin
Author information +
文章历史 +

摘要

肺动脉高压(pulmonary arterial hypertension, PAH)是一种以肺血管异常重塑和右心室压力负荷增加为特征的严重疾病,对患者健康构成重大威胁。尽管PAH的部分病理机制已被揭示,但更深入的致病机制尚待阐明。近年来,生物信息学通过多组学分析、人工智能和孟德尔随机化等技术的融合,为深入理解PAH的复杂机制提供了强有力的工具。该综述着重探讨在PAH研究中所采用的生物信息学方法和技术,总结其在疾病机制研究、诊断和预后评估方面的应用现状。此外,该文深入分析了生物信息学面临的现有挑战,以及未来其在PAH临床和基础研究领域的潜在应用。

Abstract

Pulmonary arterial hypertension (PAH) is a severe disease characterized by abnormal pulmonary vascular remodeling and increased right ventricular pressure load, posing a significant threat to patient health. While some pathological mechanisms of PAH have been revealed, the deeper mechanisms of pathogenesis remain to be elucidated. In recent years, bioinformatics has provided a powerful tool for a deeper understanding of the complex mechanisms of PAH through the integration of techniques such as multi-omics analysis, artificial intelligence, and Mendelian randomization. This review focuses on the bioinformatics methods and technologies used in PAH research, summarizing their current applications in the study of disease mechanisms, diagnosis, and prognosis assessment. Additionally, it analyzes the existing challenges faced by bioinformatics and its potential applications in the clinical and basic research fields of PAH in the future.

关键词

肺动脉高压 / 生物信息学 / 人工智能 / 机器学习

Key words

Pulmonary arterial hypertension / Bioinformatics / Artificial intelligence / Machine learning

引用本文

导出引用
彭威, 张泽盈, 肖云彬. 生物信息学在肺动脉高压中的研究进展[J]. 中国当代儿科杂志. 2024, 26(4): 425-431 https://doi.org/10.7499/j.issn.1008-8830.2310076
PENG Wei, ZHANG Ze-Ying, XIAO Yun-Bin. Research progress on bioinformatics in pulmonary arterial hypertension[J]. Chinese Journal of Contemporary Pediatrics. 2024, 26(4): 425-431 https://doi.org/10.7499/j.issn.1008-8830.2310076

参考文献

1 Vandereyken K, Sifrim A, Thienpont B, et al. Methods and applications for single-cell and spatial multi-omics[J]. Nat Rev Genet, 2023, 24(8): 494-515. PMID: 36864178. PMCID: PMC9979144. DOI: 10.1038/s41576-023-00580-2.
2 Klimontov VV, Koshechkin KA, Orlova NG, et al. Medical genetics, genomics and bioinformatics—2022[J]. Int J Mol Sci, 2023, 24(10): 8968. PMID: 37240312. PMCID: PMC10219379. DOI: 10.3390/ijms24108968.
3 Taichman DB, Leopold JA, Elliott G. Continued progress in therapy for pulmonary arterial hypertension[J]. N Engl J Med, 2023, 388(16): 1524-1526. PMID: 36876747. DOI: 10.1056/NEJMe2300324.
4 Welch CL, Chung WK. Channelopathy genes in pulmonary arterial hypertension[J]. Biomolecules, 2022, 12(2): 265. PMID: 35204766. PMCID: PMC8961593. DOI: 10.3390/biom12020265.
5 Eichstaedt CA, Sa?mannshausen Z, Shaukat M, et al. Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension[J]. Respir Res, 2022, 23(1): 74. PMID: 35346192. PMCID: PMC8962083. DOI: 10.1186/s12931-022-01987-x.
6 Hassoun PM. Pulmonary arterial hypertension[J]. N Engl J Med, 2021, 385(25): 2361-2376. PMID: 34910865. DOI: 10.1056/NEJMra2000348.
7 Salmon RM, Guo J, Wood JH, et al. Molecular basis of ALK1-mediated signalling by BMP9/BMP10 and their prodomain-bound forms[J]. Nat Commun, 2020, 11(1): 1621. PMID: 32238803. PMCID: PMC7113306. DOI: 10.1038/s41467-020-15425-3.
8 Austin ED, Elliott CG. TBX4 syndrome: a systemic disease highlighted by pulmonary arterial hypertension in its most severe form[J]. Eur Respir J, 2020, 55(5): 2000585. PMID: 32409426. DOI: 10.1183/13993003.00585-2020.
9 Gairhe S, Awad KS, Dougherty EJ, et al. Type I interferon activation and endothelial dysfunction in caveolin-1 insufficiency-associated pulmonary arterial hypertension[J]. Proc Natl Acad Sci U S A, 2021, 118(11): e2010206118. PMID: 33836561. PMCID: PMC7980434. DOI: 10.1073/pnas.2010206118.
10 Best DH, Sumner KL, Smith BP, et al. EIF2AK4 mutations in patients diagnosed with pulmonary arterial hypertension[J]. Chest, 2017, 151(4): 821-828. PMID: 27884767. DOI: 10.1016/j.chest.2016.11.014.
11 Mondéjar-Parre?o G, Cogolludo A, Perez-Vizcaino F. Potassium (K+) channels in the pulmonary vasculature: implications in pulmonary hypertension physiological, pathophysiological and pharmacological regulation[J]. Pharmacol Ther, 2021, 225: 107835. PMID: 33744261. DOI: 10.1016/j.pharmthera.2021.107835.
12 Liu M, Liu Q, Pei Y, et al. Aqp-1 gene knockout attenuates hypoxic pulmonary hypertension of mice[J]. Arterioscler Thromb Vasc Biol, 2019, 39(1): 48-62. PMID: 30580569. DOI: 10.1161/ATVBAHA.118.311714.
13 Santos-Ferreira CA, Abreu MT, Marques CI, et al. Micro-RNA analysis in pulmonary arterial hypertension: current knowledge and challenges[J]. JACC Basic Transl Sci, 2020, 5(11): 1149-1162. PMID: 33294743. PMCID: PMC7691282. DOI: 10.1016/j.jacbts.2020.07.008.
14 Zhang C, Ma C, Zhang L, et al. MiR-449a-5p mediates mitochondrial dysfunction and phenotypic transition by targeting Myc in pulmonary arterial smooth muscle cells[J]. J Mol Med (Berl), 2019, 97(3): 409-422. PMID: 30715622. DOI: 10.1007/s00109-019-01751-7.
15 Niu Z, Fu M, Li Y, et al. Osthole alleviates pulmonary vascular remodeling by modulating microRNA-22-3p mediated lipid metabolic reprogramming[J]. Phytomedicine, 2022, 96: 153840. PMID: 34836745. DOI: 10.1016/j.phymed.2021.153840.
16 Iwatani N, Kubota K, Ikeda Y, et al. Different characteristics of mitochondrial dynamics-related miRNAs on the hemodynamics of pulmonary artery hypertension and chronic thromboembolic pulmonary hypertension[J]. J Cardiol, 2021, 78(1): 24-30. PMID: 33836917. DOI: 10.1016/j.jjcc.2021.03.008.
17 Chouvarine P, Legchenko E, Geldner J, et al. Hypoxia drives cardiac miRNAs and inflammation in the right and left ventricle[J]. J Mol Med (Berl), 2019, 97(10): 1427-1438. PMID: 31338525. DOI: 10.1007/s00109-019-01817-6.
18 Ma H, Ye P, Zhang AK, et al. Upregulation of miR-335-5p contributes to right ventricular remodeling via calumenin in pulmonary arterial hypertension[J]. Biomed Res Int, 2022, 2022: 9294148. PMID: 36246958. PMCID: PMC9557250. DOI: 10.1155/2022/9294148.
19 Yen TA, Huang HC, Wu ET, et al. Microrna-486-5P regulates human pulmonary artery smooth muscle cell migration via endothelin-1[J]. Int J Mol Sci, 2022, 23(18): 10400. PMID: 36142307. PMCID: PMC9499400. DOI: 10.3390/ijms231810400.
20 Zhang J, He Y, Yan X, et al. MicroRNA-483 amelioration of experimental pulmonary hypertension[J]. EMBO Mol Med, 2020, 12(5): e11303. PMID: 32324970. PMCID: PMC7207157. DOI: 10.15252/emmm.201911303.
21 Ma Y, Chen SS, Jiang F, et al. Bioinformatic analysis and validation of microRNA-508-3p as a protective predictor by targeting NR4A3/MEK axis in pulmonary arterial hypertension[J]. J Cell Mol Med, 2021, 25(11): 5202-5219. PMID: 33942991. PMCID: PMC8178270. DOI: 10.1111/jcmm.16523.
22 Cui M, Cheng C, Zhang L. High-throughput proteomics: a methodological mini-review[J]. Lab Invest, 2022, 102(11): 1170-1181. PMID: 35922478. PMCID: PMC9362039. DOI: 10.1038/s41374-022-00830-7.
23 Singh N, Ventetuolo CE. Prime time for proteomics in pulmonary arterial hypertension risk assessment?[J]. Am J Respir Crit Care Med, 2022, 205(9): 988-990. PMID: 35143371. PMCID: PMC9851471. DOI: 10.1164/rccm.202201-0040ED.
24 Abdul-Salam VB, Wharton J, Cupitt J, et al. Proteomic analysis of lung tissues from patients with pulmonary arterial hypertension[J]. Circulation, 2010, 122(20): 2058-2067. PMID: 21041689. DOI: 10.1161/CIRCULATIONAHA.110.972745.
25 Hemnes AR, Luther JM, Rhodes CJ, et al. Human PAH is characterized by a pattern of lipid-related insulin resistance[J]. JCI insight, 2019, 4(1): e123611. PMID: 30626738. PMCID: PMC6485674. DOI: 10.1172/jci.insight.123611.
26 Rhodes CJ, Wharton J, Ghataorhe P, et al. Plasma proteome analysis in patients with pulmonary arterial hypertension: an observational cohort study[J]. Lancet Respir Med, 2017, 5(9): 717-726. PMID: 28624389. PMCID: PMC5573768. DOI: 10.1016/S2213-2600(17)30161-3.
27 Swietlik EM, Ghataorhe P, Zalewska KI, et al. Plasma metabolomics exhibit response to therapy in chronic thromboembolic pulmonary hypertension[J]. Eur Respir J, 2021, 57(4): 2003201. PMID: 33060150. PMCID: PMC8012591. DOI: 10.1183/13993003.03201-2020.
28 Harbaum L, Ghataorhe P, Wharton J, et al. Reduced plasma levels of small HDL particles transporting fibrinolytic proteins in pulmonary arterial hypertension[J]. Thorax, 2019, 74(4): 380-389. PMID: 30478197. PMCID: PMC6475111. DOI: 10.1136/thoraxjnl-2018-212144.
29 Greener JG, Kandathil SM, Moffat L, et al. A guide to machine learning for biologists[J]. Nat Rev Mol Cell Biol, 2022, 23(1): 40-55. PMID: 34518686. DOI: 10.1038/s41580-021-00407-0.
30 Krishnan R, Rajpurkar P, Topol EJ. Self-supervised learning in medicine and healthcare[J]. Nat Biomed Eng, 2022, 6(12): 1346-1352. PMID: 35953649. DOI: 10.1038/s41551-022-00914-1.
31 Bauer Y, de Bernard S, Hickey P, et al. Identifying early pulmonary arterial hypertension biomarkers in systemic sclerosis: machine learning on proteomics from the DETECT cohort[J]. Eur Respir J, 2021, 57(6): 2002591. PMID: 33334933. PMCID: PMC8276065. DOI: 10.1183/13993003.02591-2020.
32 Barrios JP, Tison GH. Advancing cardiovascular medicine with machine learning: progress, potential, and perspective[J]. Cell Rep Med, 2022, 3(12): 100869. PMID: 36543095. PMCID: PMC9798021. DOI: 10.1016/j.xcrm.2022.100869.
33 Vadapalli S, Abdelhalim H, Zeeshan S, et al. Artificial intelligence and machine learning approaches using gene expression and variant data for personalized medicine[J]. Brief Bioinform, 2022, 23(5): bbac191. PMID: 35595537. PMCID: PMC10233311. DOI: 10.1093/bib/bbac191.
34 Negi V, Yang J, Speyer G, et al. Computational repurposing of therapeutic small molecules from cancer to pulmonary hypertension[J]. Sci Adv, 2021, 7(43): eabh3794. PMID: 34669463. PMCID: PMC8528428. DOI: 10.1126/sciadv.abh3794.
35 Zhang GJ, Zhou YB. Artificial intelligence and machine learning in clinical medicine[J]. N Engl J Med, 2023, 388(25): 2397-2398. PMID: 37342935. DOI: 10.1056/NEJMc2305287.
36 Liu CM, Shih ESC, Chen JY, et al. Artificial intelligence-enabled electrocardiogram improves the diagnosis and prediction of mortality in patients with pulmonary hypertension[J]. JACC Asia, 2022, 2(3): 258-270. PMID: 36338407. PMCID: PMC9627911. DOI: 10.1016/j.jacasi.2022.02.008.
37 Alabed S, Alandejani F, Dwivedi K, et al. Validation of artificial intelligence cardiac MRI measurements: relationship to heart catheterization and mortality prediction[J]. Radiology, 2022, 305(1): 68-79. PMID: 35699578. PMCID: PMC9527336. DOI: 10.1148/radiol.212929.
38 Prohaska CC, Zhang X, Schwantes-An TL, et al. RASA3 is a candidate gene in sickle cell disease-associated pulmonary hypertension and pulmonary arterial hypertension[J]. Pulm Circ, 2023, 13(2): e12227. PMID: 37101805. PMCID: PMC10124178. DOI: 10.1002/pul2.12227.
39 Pu A, Ramani G, Chen YJ, et al. Identification of novel genetic variants, including PIM1 and LINC01491, with ICD-10 based diagnosis of pulmonary arterial hypertension in the UK Biobank cohort[J]. Front Drug Discov (Lausanne), 2023, 3: 1127736. PMID: 37089865. PMCID: PMC10121214. DOI: 10.3389/fddsv.2023.1127736.
40 Hafeez N, Kirillova A, Yue Y, et al. Single nucleotide polymorphism rs9277336 controls the nuclear alpha actinin 4-human leukocyte antigen-DPA1 axis and pulmonary endothelial pathophenotypes in pulmonary arterial hypertension[J]. J Am Heart Assoc, 2023, 12(7): e027894. PMID: 36974749. PMCID: PMC10122886. DOI: 10.1161/JAHA.122.027894.
41 Thomeas-McEwing V, Psotka MA, Gamazon ER, et al. Two polymorphic gene loci associated with treprostinil dose in pulmonary arterial hypertension[J]. Pharmacogenet Genomics, 2022, 32(4): 144-151. PMID: 35383711. DOI: 10.1097/FPC.0000000000000463.
42 Zhu N, Swietlik EM, Welch CL, et al. Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH[J]. Genome Med, 2021, 13(1): 80. PMID: 33971972. PMCID: PMC8112021. DOI: 10.1186/s13073-021-00891-1.
43 Swietlik EM, Greene D, Zhu N, et al. Bayesian inference associates rare KDR variants with specific phenotypes in pulmonary arterial hypertension[J]. Circ Genom Precis Med, 2020, 14(1): e003155. PMID: 33320693. PMCID: PMC7892262. DOI: 10.1161/CIRCGEN.120.003155.
44 Hodgson J, Swietlik EM, Salmon RM, et al. Characterization of GDF2 mutations and levels of BMP9 and BMP10 in pulmonary arterial hypertension[J]. Am J Respir Crit Care Med, 2020, 201(5): 575-585. PMID: 31661308. PMCID: PMC7047445. DOI: 10.1164/rccm.201906-1141OC.
45 Wang XJ, Xu XQ, Sun K, et al. Association of rare PTGIS variants with susceptibility and pulmonary vascular response in patients with idiopathic pulmonary arterial hypertension[J]. JAMA Cardiol, 2020, 5(6): 677-684. PMID: 32236489. PMCID: PMC7113838. DOI: 10.1001/jamacardio.2020.0479.
46 Ulrich A, Otero-Nú?ez P, Wharton J, et al. Expression quantitative trait locus mapping in pulmonary arterial hypertension[J]. Genes (Basel), 2020, 11(11): 1247. PMID: 33105808. PMCID: PMC7690609. DOI: 10.3390/genes11111247.
47 Rhodes CJ, Batai K, Bleda M, et al. Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis[J]. Lancet Respir Med, 2019, 7(3): 227-238. PMID: 30527956. PMCID: PMC6391516. DOI: 10.1016/S2213-2600(18)30409-0.
48 Molvin J, Jujic A, Nilsson PM, et al. A diabetes-associated genetic variant is associated with diastolic dysfunction and cardiovascular disease[J]. ESC Heart Fail, 2020, 7(1): 348-356. PMID: 31860786. PMCID: PMC7083427. DOI: 10.1002/ehf2.12573.
49 Ramírez J, van Duijvenboden S, Aung N, et al. Cardiovascular predictive value and genetic basis of ventricular repolarization dynamics[J]. Circ Arrhythm Electrophysiol, 2019, 12(10): e007549. PMID: 31607149. DOI: 10.1161/CIRCEP.119.007549.
50 Zhang M, Zeng Q, Zhou S, et al. Mendelian randomization study on causal association of IL-6 signaling with pulmonary arterial hypertension[J]. Clin Exp Hypertens, 2023, 45(1): 2183963. PMID: 36871578. DOI: 10.1080/10641963.2023.2183963.

基金

国家自然科学基金(81500041);湖南省儿童心血管病临床医学研究中心(2021SK4019);湖南省研究生科研创新项目(CX20231013)。

PDF(532 KB)
HTML

Accesses

Citation

Detail

段落导航
相关文章

/