Unraveling the Dysbiosis of Vaginal Microbiome to Understand Cervical Cancer Disease Etiology-An Explainable AI Approach

被引:6
作者
Sekaran, Karthik [1 ]
Varghese, Rinku Polachirakkal [1 ]
Gopikrishnan, Mohanraj [1 ]
Alsamman, Alsamman M. [2 ]
Allali, Achraf El [3 ]
Zayed, Hatem [4 ]
Doss, C. George Priya [1 ]
机构
[1] Vellore Inst Technol, Sch Biosci & Technol, Vellore 632014, India
[2] Agr Genet Engn Res Inst, Genome Mapping Dept, Mol Genet & Genome Mapping Lab, Cairo 12619, Egypt
[3] Mohammed VI Polytech Univ, African Genome Ctr, Ben Guerir 43150, Morocco
[4] Qatar Univ, Coll Hlth Sci, Dept Biomed Sci, QU Hlth, Doha, Qatar
关键词
cervical cancer; eXplainable AI; vaginal microbiome; SHapley Additive exPlanations; HUMAN-PAPILLOMAVIRUS INFECTION; INTRAEPITHELIAL NEOPLASIA; RISK; DIVERSITY; HPV; PERSISTENCE; PROGRESSION; COMMUNITY; SMOKING;
D O I
10.3390/genes14040936
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Microbial Dysbiosis is associated with the etiology and pathogenesis of diseases. The studies on the vaginal microbiome in cervical cancer are essential to discern the cause and effect of the condition. The present study characterizes the microbial pathogenesis involved in developing cervical cancer. Relative species abundance assessment identified Firmicutes, Actinobacteria, and Proteobacteria dominating the phylum level. A significant increase in Lactobacillus iners and Prevotella timonensis at the species level revealed its pathogenic influence on cervical cancer progression. The diversity, richness, and dominance analysis divulges a substantial decline in cervical cancer compared to control samples. The beta diversity index proves the homogeneity in the subgroups' microbial composition. The association between enriched Lactobacillus iners at the species level, Lactobacillus, Pseudomonas, and Enterococcus genera with cervical cancer is identified by Linear discriminant analysis Effect Size (LEfSe) prediction. The functional enrichment corroborates the microbial disease association with pathogenic infections such as aerobic vaginitis, bacterial vaginosis, and chlamydia. The dataset is trained and validated with repeated k-fold cross-validation technique using a random forest algorithm to determine the discriminative pattern from the samples. SHapley Additive exPlanations (SHAP), a game theoretic approach, is employed to analyze the results predicted by the model. Interestingly, SHAP identified that the increase in Ralstonia has a higher probability of predicting the sample as cervical cancer. New evidential microbiomes identified in the experiment confirm the presence of pathogenic microbiomes in cervical cancer vaginal samples and their mutuality with microbial imbalance.
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页数:15
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