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Deep vein thrombosis (DVT) is a serious health issue that often leads to considerable morbidity and mortality. Diagnosis of DVT in a clinical setting, however, presents considerable challenges. The fusion of metabolomics techniques and machine learning methods has led to high diagnostic and prognostic accuracy for various pathological conditions. This study explored the synergistic potential of dual-platform metabolomics (specifically, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)) to expand the detection of metabolites and improve the precision of DVT diagnosis. Sixty-one differential metabolites were identified in serum from DVT patients: 22 from GC-MS and 39 from LC-MS. Among these, five key metabolites were highlighted by SHapley Additive exPlanations (SHAP)-guided feature engineering and then used to develop a stacking diagnostic model. Additionally, a user-friendly interface application system was developed to streamline and automate the application of the diagnostic model, enhancing its practicality and accessibility for clinical use. This work showed that the integration of dual-platform metabolomics with a stacking machine learning model enables faster and more accurate diagnosis of DVT in clinical environments.
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The microbial communities may undergo a meaningful successional change during the progress of decay and decomposition that could aid in determining the post-mortem interval (PMI). However, there are still challenges to applying microbiome-based evidence in law enforcement practice. In this study, we attempted to investigate the principles governing microbial community succession during decomposition of rat and human corpse, and explore their potential use for PMI of human cadavers. A controlled experiment was conducted to characterize temporal changes in microbial communities associated with rat corpses as they decomposed for 30 days. Obvious differences of microbial community structures were observed among different stages of decomposition, especially between decomposition of 0-7d and 9-30d. Thus, a two-layer model for PMI prediction was developed based on the succession of bacteria by combining classification and regression models using machine learning algorithms. Our results achieved 90.48% accuracy for discriminating groups of PMI 0-7d and 9-30d, and yielded a mean absolute error of 0.580d within 7d decomposition and 3.165d within 9-30d decomposition. Furthermore, samples from human cadavers were collected to gain the common succession of microbial community between rats and humans. Based on the 44 shared genera of rats and humans, a two-layer model of PMI was rebuilt to be applied for PMI prediction of human cadavers. Accurate estimates indicated a reproducible succession of gut microbes across rats and humans. Together these results suggest that microbial succession was predictable and can be developed into a forensic tool for estimating PMI.
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Microbioma Gastrointestinal , Microbiota , Humanos , Ratas , Animales , Cambios Post Mortem , Cadáver , Aprendizaje AutomáticoRESUMEN
The determination of sudden cardiac death (SCD) is one of the difficult tasks in the forensic practice, especially in the absence of specific morphological changes in the autopsies and histological investigations. In this study, we combined the metabolic characteristics from corpse specimens of cardiac blood and cardiac muscle to predict SCD. Firstly, ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS)-based untargeted metabolomics was applied to obtain the metabolomic profiles of the specimens, and 18 and 16 differential metabolites were identified in the cardiac blood and cardiac muscle from the corpses of those who died of SCD, respectively. Several possible metabolic pathways were proposed to explain these metabolic alterations, including the metabolism of energy, amino acids, and lipids. Then, we validated the capability of these combinations of differential metabolites to distinguish between SCD and non-SCD through multiple machine learning algorithms. The results showed that stacking model integrated differential metabolites featured from the specimens showed the best performance with 92.31% accuracy, 93.08% precision, 92.31% recall, 91.96% F1 score, and 0.92 AUC. Our results revealed that the SCD metabolic signature identified by metabolomics and ensemble learning in cardiac blood and cardiac muscle has potential in SCD post-mortem diagnosis and metabolic mechanism investigations.
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Metaboloma , Metabolómica , Humanos , Metabolómica/métodos , Espectrometría de Masas/métodos , Cromatografía Líquida de Alta Presión , Muerte Súbita CardíacaRESUMEN
Determining postmortem interval (PMI) is one of the most challenging and essential endeavors in forensic science. Developments in PMI estimation can take advantage of machine learning techniques. Currently, applying an algorithm to obtain information on multiple organs and conducting joint analysis to accurately estimate PMI are still in the early stages. This study aimed to establish a multi-organ stacking model that estimates PMI by analyzing differential compounds of four organs in rats. In a total of 140 rats, skeletal muscle, liver, lung, and kidney tissue samples were collected at each time point after death. Ultra-performance liquid chromatography coupled with high-resolution mass spectrometry was used to determine the compound profiles of the samples. The original data were preprocessed using multivariate statistical analysis to determine discriminant compounds. In addition, three interrelated and increasingly complex patterns (single organ optimal model, single organ stacking model, multi-organ stacking model) were established to estimate PMI. The accuracy and generalized area under the receiver operating characteristic curve of the multi-organ stacking model were the highest at 93% and 0.96, respectively. Only 1 of the 14 external validation samples was misclassified by the multi-organ stacking model. The results demonstrate that the application of the multi-organ combination to the stacking algorithm is a potential forensic tool for the accurate estimation of PMI.
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Metabolómica , Cambios Post Mortem , Ratas , Animales , Ratas Sprague-Dawley , Autopsia , Metabolómica/métodos , Aprendizaje AutomáticoRESUMEN
Acute myocardial ischemia (AMI) remains the leading cause of death worldwide, and the post-mortem diagnosis of AMI represents a current challenge for both clinical and forensic pathologists. In the present study, the untargeted metabolomics based on ultra-performance liquid chromatography combined with high-resolution mass spectrometry was applied to analyze serum metabolic signatures from AMI in a rat model (n = 10 per group). A total of 28 endogenous metabolites in serum were significantly altered in AMI group relative to control and sham groups. A set of machine learning algorithms, namely gradient tree boosting (GTB), support vector machine (SVM), random forest (RF), logistic regression (LR), and multilayer perceptron (MLP) models, was used to screen the more valuable metabolites from 28 metabolites to optimize the biomarker panel. The results showed that classification accuracy and performance of MLP model were better than other algorithms when the metabolites consisting of L-threonic acid, N-acetyl-L-cysteine, CMPF, glycocholic acid, L-tyrosine, cholic acid, and glycoursodeoxycholic acid. Finally, 17 blood samples from autopsy cases were applied to validate the classification model's value in human samples. The MLP model constructed based on rat dataset achieved accuracy of 88.23%, and ROC of 0.89 for predicting AMI type II in autopsy cases of sudden cardiac death. The results demonstrated that MLP model based on 7 molecular biomarkers had a good diagnostic performance for both AMI rats and autopsy-based blood samples. Thus, the combination of metabolomics and machine learning algorithms provides a novel strategy for AMI diagnosis.
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Algoritmos , Isquemia Miocárdica , Humanos , Ratas , Animales , Aprendizaje Automático , Isquemia Miocárdica/diagnóstico , Metabolómica , Biomarcadores , Máquina de Vectores de SoporteRESUMEN
OBJECTIVES: To explore the correlation between intestinal microbiota and postmortem interval(PMI) in rats by using 16S rRNA high-throughput sequencing technology. METHODS: Rats were killed by anesthesia and placed at 16 â, and DNA was extracted in caecum at 14 time points of 0, 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 24, 27 and 30 d after death. The 16S rRNA high-throughput sequencing technology was used to detect intestinal microbiota in rat cecal contents, and the results were used to analyze the rat intestinal microbiota diversity and differences. RESULTS: The total number of intestinal microbial communities did not change significantly within 30 days after death, but the diversity showed an upward trend. A total of 119 bacterial communities were significantly changed at 13 time points after death. The models for PMI estimation were established by using partial least squares (PLS) regression at all time points, before 9 days and after 12 days, reaching an R2 of 0.795, 0.767 and 0.445, respectively; and the root mean square errors (RMSEs) were 6.57, 1.96 and 5.37 d, respectively. CONCLUSIONS: Using 16S rRNA high-throughput sequencing technology, the composition and structure of intestinal microbiota changed significantly within 30 d after death. In addition, the established PLS regression model suggested that the PMI was highly correlated with intestinal microbiota composition, showing a certain time series change.
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Microbioma Gastrointestinal , Microbiota , Animales , Microbioma Gastrointestinal/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Microbiota/genética , Cambios Post Mortem , ARN Ribosómico 16S/genética , Ratas , TecnologíaRESUMEN
Wound age estimation is a complex, multifactorial issue. It is considered to have great practical significance that combining multi-biomarkers and multi-methods for injury time estimation. We optimized our earlier "up, no change, or down" model by adding data on the expression levels of mRNAs encoding ABHD2, MAD2L2, and ARID5A, and we converted the relative quantitative expression levels of seven genes into a vector rather than a color model. We used Python to derive the cosine similarity (CS) between a test set and the vector matrix; the highest similarity most accurately reflected the injury time. For the optimized model, the internal and external verifications were approximately 0.71 and 0.66, respectively. The good double-blinded results indicated that the model was stable and reliable. In summary, we used a vector matrix and cosine similarities derived by Python to mine the levels of genes expressed in contused skeletal muscle. We are the first to combine several biomarkers and methods for wound age estimation.