Establishment of artificial neural network model based on mitochondria-associated genes in Crohn's disease

DU Fengming; CAO Xiaohua; LIU Ruichen; HU Chaoyang; SUN Yan

doi:10.7619/jcmp.20242822

Journal of Clinical Medicine in Practice > 2024 > 28(23): 8-15. > DOI: 10.7619/jcmp.20242822

DU Fengming, CAO Xiaohua, LIU Ruichen, HU Chaoyang, SUN Yan. Establishment of artificial neural network model based on mitochondria-associated genes in Crohn's disease[J]. Journal of Clinical Medicine in Practice, 2024, 28(23): 8-15. DOI: 10.7619/jcmp.20242822

Citation:

PDF (6085 KB)

Establishment of artificial neural network model based on mitochondria-associated genes in Crohn's disease

1.
College of Management, Shanxi Medical University, Taiyuan, Shanxi, 030600
2.
College of Basic Medicine, Shanxi Medical University, Taiyuan, Shanxi, 030600

More Information

Received Date: July 02, 2024
Revised Date: September 17, 2024

Graphical Abstract

Abstract

Abstract

Objective
To screen mitochondria-related genes in Crohn's disease (CD) based on the Gene Expression Omnibus (GEO) database, construct an artificial neural network diagnostic model and evaluate its performance.
Methods
The CD-related datasets GSE186582 and GSE102133 were downloaded from the GEO database for differential expression genes (DEGs) screening. The intersection of DEGs and mitochondrial genes from the MitoCarta 3.0 database was obtained. Least absolute shrinkage and selection operator regression and random forest algorithms were used to identify CD-specific genes and construct an artificial neural network diagnostic model. The model was further validated by the validation set GSE95095, and the diagnostic performance was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve. The immune cell infiltration in CD was assessed by the CIBERSORT algorithm, and the relationship between biomarkers and infiltrated immune cells was investigated.
Results
A total of 551 DEGs were obtained, including 275 upregulated and 276 downregulated genes. There were 20 mitochondria-related genes associated with CD. A total of 9 mitochondria-related feature genes (SOD2, MTHFD2, BPHL, PXMP2, RMND1, AGXT2, MAOA, HMGCS2, MAOB) were screened by two machine learning algorithms. An artificial neural network diagnostic model was constructed by the selected feature genes. The values of AUC of the model in the training and validation groups were 0.956 and 0.736 respectively. Immune cell infiltration analysis showed that the feature genes were associated with resting memory CD4⁺ T cells, activated memory CD4⁺ T cells, activated dendritic cells, neutrophils, and CD8⁺ T cells.
Conclusion
The artificial neural network diagnostic model for CD based on 9 mitochondrial genes has good predictive performance.
- Crohn's disease,
- mitochondria,
- artificial neural network,
- machine learning,
- differential analysis,
- immune cell infiltration

FullText(HTML)

References (37)

References

[1]	TAVASSOLIFAR M J, CHANGAEI M, SALEHI Z, et al. Redox imbalance in Crohn's disease patients is modulated by Azathioprine[J]. Redox Rep, 2021, 26(1): 80-84. doi: 10.1080/13510002.2021.1915665
[2]	AMODEO G, FRANCHI S, GALIMBERTI G, et al. The prokineticin system in inflammatory bowel diseases: a clinical and preclinical overview[J]. Biomedicines, 2023, 11(11): 2985. doi: 10.3390/biomedicines11112985
[3]	苏培强, 钟壮霞, 陈益耀, 等. 胞外-5'-核苷酸酶在克罗恩病小鼠结肠组织中的表达及意义[J]. 中国热带医学, 2023, 23(10): 1071-1076.
[4]	NAYAR S, MORRISON J K, GIRI M, et al. A myeloid-stromal niche and gp130 rescue in NOD2-driven Crohn's disease[J]. Nature, 2021, 593(7858): 275-281. doi: 10.1038/s41586-021-03484-5
[5]	PETAGNA L, ANTONELLI A, GANINI C, et al. Pathophysiology of Crohn's disease inflammation and recurrence[J]. Biol Direct, 2020, 15(1): 23. doi: 10.1186/s13062-020-00280-5
[6]	KANG Y, PARK H, CHOE B H, et al. The role and function of mucins and its relationship to inflammatory bowel disease[J]. Front Med, 2022, 9: 848344. doi: 10.3389/fmed.2022.848344
[7]	CROSS E, PRIOR J A, FARMER A D, et al. Patients'views and experiences of delayed diagnosis of inflammatory bowel disease: a qualitative study[J]. BJGP Open, 2023, 7(4): BJGPO. 2023, 70: 1-10.
[8]	SÁNCHEZ-QUINTERO M J, RODRÍGUEZ-DÍAZ C, RODRÍGUEZ-GONZÁLEZ F J, et al. Role of mitochondria in inflammatory bowel diseases: a systematic review[J]. Int J Mol Sci, 2023, 24(23): 17124. doi: 10.3390/ijms242317124
[9]	HO G T, THEISS A L. Mitochondria and inflammatory bowel diseases: toward a stratified therapeutic intervention[J]. Annu Rev Physiol, 2022, 84: 435-459. doi: 10.1146/annurev-physiol-060821-083306
[10]	NUNNARI J, SUOMALAINEN A. Mitochondria: in sickness and in health[J]. Cell, 2012, 148(6): 1145-1159. doi: 10.1016/j.cell.2012.02.035
[11]	BLAGOV A, ZHIGMITOVA E B, SAZONOVA M A, et al. Novel models of Crohn's disease pathogenesis associated with the occurrence of mitochondrial dysfunction in intestinal cells[J]. Int J Mol Sci, 2022, 23(9): 5141. doi: 10.3390/ijms23095141
[12]	RATH S, SHARMA R, GUPTA R, et al. MitoCarta3. 0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations[J]. Nucleic Acids Res, 2021, 49(D1): D1541-D1547. doi: 10.1093/nar/gkaa1011
[13]	吴胜男, 蒋环宇, 陈浩然, 等. 基于生物信息学分析溃疡性结肠炎的差异表达基因和相关微小RNA[J]. 实用临床医药杂志, 2024, 28(1): 48-55.
[14]	ALI H, SHAHZAD M, SARFRAZ S, et al. Application and impact of Lasso regression in gastroenterology: a systematic review[J]. Indian J Gastroenterol, 2023, 42(6): 780-790. doi: 10.1007/s12664-023-01426-9
[15]	TOTH R, SCHIFFMANN H, HUBE-MAGG C, et al. Random forest-based modelling to detect biomarkers for prostate cancer progression[J]. Clin Epigenetics, 2019, 11(1): 148. doi: 10.1186/s13148-019-0736-8
[16]	左志威, 孟庆良, 崔家康, 等. 基于硬皮病线粒体相关基因的人工神经网络模型的构建[J]. 南方医科大学学报, 2024, 44(5): 920-929.
[17]	KAWADA J I, TAKEUCHI S, IMAI H, et al. Immune cell infiltration landscapes in pediatric acute myocarditis analyzed by CIBERSORT[J]. J Cardiol, 2021, 77(2): 174-178. doi: 10.1016/j.jjcc.2020.08.004
[18]	KMIECZ, CYMAN M, SLEBIODA T J. Cells of the innate and adaptive immunity and their interactions in inflammatory bowel disease[J]. Adv Med Sci, 2017, 62(1): 1-16. doi: 10.1016/j.advms.2016.09.001
[19]	ALATEYAH N, GUPTA I, RUSYNIAK R S, et al. SOD2, a potential transcriptional target underpinning CD44-promoted breast cancer progression[J]. Molecules, 2022, 27(3): 811. doi: 10.3390/molecules27030811
[20]	MELEK J, STANCLOVÁM, DÉDEK P, et al. Infliximab plus azathioprine is more effective than azathioprine alone in achieving mucosal healing in pediatric patients with Crohn's disease[J]. J Dig Dis, 2020, 21(12): 705-710. doi: 10.1111/1751-2980.12927
[21]	SHANG M, NI L N, SHAN X, et al. MTHFD2 reprograms macrophage polarization by inhibiting PTEN[J]. Cell Rep, 2023, 42(5): 112481. doi: 10.1016/j.celrep.2023.112481
[22]	SUGIURA A, ANDREJEVA G, VOSS K, et al. MTHFD2 is a metabolic checkpoint controlling effector and regulatory Tcell fate and function[J]. Immunity, 2022, 55(1): 65-81, e9. doi: 10.1016/j.immuni.2021.10.011
[23]	TANG H, HOU N. Whether MTHFD2 plays a new role: from anticancer targets to anti-inflammatory disease[J]. Front Pharmacol, 2023, 14: 1257107. doi: 10.3389/fphar.2023.1257107
[24]	REN P F, ZHAI J X, WANG X L, et al. Inhibition of BPHL inhibits proliferation in lung carcinoma cell lines[J]. Transl Lung Cancer Res, 2023, 12(5): 1051-1061. doi: 10.21037/tlcr-23-225
[25]	BOROS E, ELILIÉ MAWA ONGOTH F, HEINRICHS C, et al. Primary ovarian insufficiency in RMND1 mitochondrial disease[J]. Mitochondrion, 2022, 66: 51-53. doi: 10.1016/j.mito.2022.07.004
[26]	KÖMHOFF M, GRACCHI V, DIJKMAN H, et al. Hyporeninemic hypoaldosteronism in RMND1-related mitochondrial disease[J]. Pediatr Nephrol, 2024, 39(1): 125-129. doi: 10.1007/s00467-023-06079-6
[27]	KUMON H, MIYAKE Y, YOSHINO Y, et al. Functional AGXT2 SNP rs180749 variant and depressive symptoms: baseline data from the Aidai Cohort Study in Japan[J]. J Neural Transm, 2024, 131(3): 267-274. doi: 10.1007/s00702-024-02742-w
[28]	DATTA C, DAS P, DUTTA S, et al. AMPK activation reduces cancer cell aggressiveness via inhibition of monoamine oxidase A (MAO-A) expression/activity[J]. Life Sci, 2024, 352: 122857. doi: 10.1016/j.lfs.2024.122857
[29]	NAM M H, NA H, JUSTIN LEE C, et al. A key mediator and imaging target in Alzheimer's disease: unlocking the role of reactive astrogliosis through MAOB[J]. Nucl Med Mol Imaging, 2024, 58(4): 177-184. doi: 10.1007/s13139-023-00837-y
[30]	CHEN D L, RUAN X, LIU Y, et al. HMGCS₂ silencing attenuates high glucose-induced in vitro diabetic cardiomyopathy by increasing cell viability, and inhibiting apoptosis, inflammation, and oxidative stress[J]. Bioengineered, 2022, 13(5): 11417-11429. doi: 10.1080/21655979.2022.2063222
[31]	ZOU X Z, HAO J F, HOU M X. Hmgcs2 regulates M2 polarization of macrophages to repair myocardial injury induced by sepsis[J]. Aging, 2023, 15(15): 7794-7810.
[32]	LI Q, HUANG Z C, YANG H S, et al. Intestinal mRNA expression profiles associated with mucosal healing in ustekinumab-treated Crohn's disease patients: bioinformatics analysis and prospective cohort validation[J]. J Transl Med, 2024, 22(1): 595. doi: 10.1186/s12967-024-05427-w
[33]	SENSI B, SIRAGUSA L, EFRATI C, et al. The role of inflammation in Crohn's disease recurrence after surgical treatment[J]. J Immunol Res, 2020, 2020: 8846982.
[34]	LI N, SHI R H. Updated review on immune factors in pathogenesis of Crohn's disease[J]. World J Gastroenterol, 2018, 24(1): 15-22. doi: 10.3748/wjg.v24.i1.15
[35]	THERRIEN A, CHAPUY L, BSAT M, et al. Recruitment of activated neutrophils correlates with disease severity in adult Crohn's disease[J]. Clin Exp Immunol, 2019, 195(2): 251-264. doi: 10.1111/cei.13226
[36]	AYDEMIR Y, PINAR A, HIZAL G, et al. Neutrophil volume distribution width as a new marker in detecting inflammatory bowel disease activation[J]. Int J Lab Hematol, 2017, 39(1): 51-57. doi: 10.1111/ijlh.12574
[37]	SAEZ A, HERRERO-FERNANDEZ B, GOMEZ-BRIS R, et al. Pathophysiology of inflammatory bowel disease: innate immune system[J]. Int J Mol Sci, 2023, 24(2): 1526. doi: 10.3390/ijms24021526

Cited By

Cited by

Periodical cited type(14)

1.	李小叶，李德忠，刘叶君. 白细胞介素及胎儿纤维连接蛋白水平对早产的预测价值. 中国医师杂志. 2022(01): 101-104 .
2.	郝灿灿. 硝苯地平联合盐酸利托君治疗先兆早产的临床研究. 大医生. 2022(20): 29-31 .
3.	马依努·阿尔沙. 盐酸利托君配伍紧急宫颈环扎治疗晚期难免流产的效果. 中国继续医学教育. 2021(25): 149-153 .
4.	张红敏，宋继荣. 先兆早产患者应用盐酸利托君和硫酸镁的临床价值对比. 海峡药学. 2020(01): 146-147 .
5.	费腾. 分析不同宫缩抑制剂治疗先兆早产患者的疗效及对产妇和围生儿结局的影响. 中国医药指南. 2020(19): 52-53 .
6.	罗丽萍，童焰. 硫酸镁联合盐酸利托君在胎膜早破患者中的疗效观察及对妊娠结局的影响研究. 当代医学. 2019(30): 157-158 .
7.	冯敏. 利托君治疗胎膜早破型先兆早产的临床效果观察. 中外医学研究. 2019(30): 129-130 .
8.	张青霞，吴思懿，吴莹莹. 盐酸利托君治疗先兆早产的临床效果观察. 临床合理用药杂志. 2019(35): 82-83 .
9.	莫小跃，吴敏. 盐酸利托君与硫酸镁治疗先兆早产的效果及不良反应探讨. 中国医药科学. 2018(05): 79-81+98 .
10.	沈雪艳，张国华，张微. 乳杆菌对先兆早产患者生殖道免疫微环境的影响及意义. 山东医药. 2018(28): 83-85 .
11.	李翠丽. 盐酸利托君对于早产胎膜早破患者的临床治疗效果探究. 天津药学. 2018(03): 39-41 .
12.	亓露，齐慧丽. 盐酸利托君在妊娠期糖尿病孕妇先兆早产中的应用. 北方药学. 2018(12): 48-49 .
13.	魏然. 保胎灵胶囊辅助治疗先兆早产的可行性分析. 实用中西医结合临床. 2018(12): 135-137 .
14.	王慧娟. 硝苯地平与盐酸利托君在早产产妇中的应用效果及安全性比较. 临床医学. 2017(12): 113-114 .

Other cited types(1)

Get Citation

PDF

XML

Article views (140) PDF downloads (27) Cited by(15)

Turn off MathJax

Article Contents

Abstract

References

Establishment of artificial neural network model based on mitochondria-associated genes in Crohn's disease

Abstract

References

Cited by

Periodical cited type(14)

Other cited types(1)

Catalog

Export File

Citation

Format

Content