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Cell morphology-based machine learning models for human cell state classification.

ABSTRACT: Herein, we implement and access machine learning architectures to ascertain models that differentiate healthy from apoptotic cells using exclusively forward (FSC) and side (SSC) scatter flow cytometry information. To generate training data, colorectal cancer HCT116 cells were subjected to miR-34a treatment and then classified using a conventional Annexin V/propidium iodide (PI)-staining assay. The apoptotic cells were defined as Annexin V-positive cells, which include early and late apoptotic cells, necrotic cells, as well as other dying or dead cells. In addition to fluorescent signal, we collected cell size and granularity information from the FSC and SSC parameters. Both parameters are subdivided into area, height, and width, thus providing a total of six numerical features that informed and trained our models. A collection of logistical regression, random forest, k-nearest neighbor, multilayer perceptron, and support vector machine was trained and tested for classification performance in predicting cell states using only the six aforementioned numerical features. Out of 1046 candidate models, a multilayer perceptron was chosen with 0.91 live precision, 0.93 live recall, 0.92 live f value and 0.97 live area under the ROC curve when applied on standardized data. We discuss and highlight differences in classifier performance and compare the results to the standard practice of forward and side scatter gating, typically performed to select cells based on size and/or complexity. We demonstrate that our model, a ready-to-use module for any flow cytometry-based analysis, can provide automated, reliable, and stain-free classification of healthy and apoptotic cells using exclusively size and granularity information.

SUBMITTER: Li Y

PROVIDER: S-EPMC8155075 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In recent years, functional brain network topological features have been widely used as classification features. Previous studies have found that network node scale differences caused by different network parcellation definitions significantly affect the structure of the constructed network and its topological properties. However, we still do not know how network scale differences affect the classification accuracy, performance of classification features, and effectiveness of the feature selection strategy using P values in terms of the machine learning method. This study used five scale parcellations, involving 90, 256, 497, 1003, and 1501 nodes. Three local properties of resting-state functional brain networks were selected (degree, betweenness centrality, and nodal efficiency), and the support vector machine method was used to construct classifiers to identify patients with major depressive disorder. We analyzed the impact of the five scales on classification accuracy. In addition, the effectiveness and redundancy of features obtained by the different scale parcellations were compared. Finally, traditional statistical significance (P value) was verified as a feature selection criterion. The results showed that the feature effectiveness of different scales was similar; in other words, parcellation with more regions did not provide more effective discriminative features. Nevertheless, parcellation with more regions did provide a greater quantity of discriminative features, which led to an improvement in the accuracy of the classification. However, due to the close distance between brain regions, the redundancy of parcellation with more regions was also greater. The traditional P value feature selection strategy is feasible with different scales, but our analysis showed that the traditional P < 0.05 threshold was too strict for feature selection. This study provides an important reference for the selection of network scales when applying topological properties of brain networks to machine learning methods.

Project description:Background:To evaluate the association of multiparametric and multiregional MRI-features with key molecular characteristics in patients with newly-diagnosed glioblastoma. Methods:Retrospective data evaluation was approved by the local ethics committee of the University of Heidelberg (ethics approval number: S-320/2012) and informed consent was waived. Preoperative MRI-features were correlated with key molecular characteristics within a single-institutional cohort of 152 patients with newly-diagnosed glioblastoma. Preoperative MRI-features (n=31) included multiparametric (anatomical, diffusion-, perfusion-, and susceptibility-weighted images) and multiregional (contrast enhancing and non-enhancing FLAIR-hyperintense) information with (histogram) quantification of tumor volumes, volume ratios, apparent diffusion coefficients, cerebral blood flow / volume (CBF / CBV) and intratumoral susceptibility signals. Molecular characteristics determined with the Illumina Infinium HumanMethylation450 array included global DNA-methylation subgroups (e.g. mesenchymal (MES), RTK I “PGFRA”, RTK II “classic”), MGMT-promoter methylation status and hallmark copy-number-variations (EGFR-, PDGFRA-, MDM4- and CDK4-amplification; PTEN-, CDKN2A-, NF1- and RB1-loss). Univariate analyses (voxel-lesion-symptom-mapping for tumor location, Wilcoxon-test for all other MRI-features) as well as machine-learning models were applied to study the strength of association and discriminative value of MRI-features for predicting underlying molecular characteristics. Results: There was no tumor location predilection for any of the assessed molecular parameters (permutation-adjusted p>0.05 each). Univariate imaging parameter associations were noted for EGFR amplification and CDKN2A loss, both demonstrating increased nrCBV and nrCBF values (performance of these parameters, as assessed by the area under the ROC curve ranged from 63 to 69%, FDR-adjusted p<0.05, respectively). Subjecting all MRI-features to machine-learning-based classification allowed to predict EGFR amplification status and the RTK II “classic” GB subgroup with a moderate, yet significantly greater accuracy (63% for EGFR [p<0.01] and 61% for RTK II [p=0.01]) than the prediction by chance, whereas prediction accuracy for all other molecular parameters was non-significant (p>0.05, all models). Conclusions: In summary, we found univariate associations between established MRI-features and molecular characteristics, however not of sufficient strength to allow the generation of machine-learning classification models for reliable and clinically meaningful prediction of the assessed molecular characteristics in patients with newly-diagnosed glioblastoma.

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Cell morphology-based machine learning models for human cell state classification.

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