A 6-gene panel as a signature to predict recovery from advanced heart failure using transcriptomic analysis

Zou, Shangjie; Khoo, Bee Luan

doi:10.1016/j.gendis.2021.12.001

Cited by 2 publications

(2 citation statements)

References 5 publications

(7 reference statements)

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“…These findings serve as clear evidence of the potential of our system in identifying phenotypic heterogeneity and in practical applications 33 , such as patient stratification or staging based on metastatic potential.…”

Section: Resultsmentioning

confidence: 69%

A deformability-based biochip for precise label-free stratification of metastatic subtypes using deep learning

Hua,

Zou,

et al. 2023

Microsyst Nanoeng

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Cellular deformability is a promising biomarker for evaluating the physiological state of cells in medical applications. Microfluidics has emerged as a powerful technique for measuring cellular deformability. However, existing microfluidic-based assays for measuring cellular deformability rely heavily on image analysis, which can limit their scalability for high-throughput applications. Here, we develop a parallel constriction-based microfluidic flow cytometry device and an integrated computational framework (ATMQcD). The ATMQcD framework includes automatic training set generation, multiple object tracking, segmentation, and cellular deformability quantification. The system was validated using cancer cell lines of varying metastatic potential, achieving a classification accuracy of 92.4% for invasiveness assessment and stratifying cancer cells before and after hypoxia treatment. The ATMQcD system also demonstrated excellent performance in distinguishing cancer cells from leukocytes (accuracy = 89.5%). We developed a mechanical model based on power-law rheology to quantify stiffness, which was fitted with measured data directly. The model evaluated metastatic potentials for multiple cancer types and mixed cell populations, even under real-world clinical conditions. Our study presents a highly robust and transferable computational framework for multiobject tracking and deformation measurement tasks in microfluidics. We believe that this platform has the potential to pave the way for high-throughput analysis in clinical applications, providing a powerful tool for evaluating cellular deformability and assessing the physiological state of cells.

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Section: Resultsmentioning

confidence: 69%

A deformability-based biochip for precise label-free stratification of metastatic subtypes using deep learning

Hua,

Zou,

et al. 2023

Microsyst Nanoeng

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“…Mitochondrial dysfunction secondary to oxidative stress has been demonstrated to drive the pathogenesis of numerous retinal diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO) (8)(9)(10)(11). Oxidative stress results from the accumulation of reactive oxygen species that exceeds the antioxidant defense capacity of the cell (12). In healthy cells, reactive oxygen species are scavenged by antioxidant enzymes like manganese superoxide dismutase (5).…”

Section: Introductionmentioning

confidence: 99%

Flavoprotein fluorescence elevation is a marker of mitochondrial oxidative stress in patients with retinal disease

et al. 2023

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PurposeRecent studies of glaucoma, age-related macular degeneration, and diabetic retinopathy have demonstrated that flavoprotein fluorescence (FPF) can be utilized non-invasively as an indicator of mitochondrial oxidative stress in the retina. However, a comprehensive assessment of the validity and reliability of FPF in differentiating between healthy and diseased eyes across multiple disease states is lacking. Here, we evaluate the sensitivity and specificity of FPF in discriminating between healthy and diseased eyes in four leading causes of visual impairment worldwide, one of which has not been previously evaluated using FPF. We also evaluate the association between FPF and visual acuity.MethodsA total of 88 eyes [21 eyes of 21 unaffected controls, 20 eyes from 20 retinal vein occlusion (RVO) patients, 20 eyes from 20 diabetic retinopathy (DR) patients, 17 eyes from 17 chronic exudative age-related macular degeneration (exudative AMD) patients, and 10 eyes from 10 central serous retinopathy (CSR) patients] were included in the present cross-sectional observational study. Eyes were imaged non-invasively using a specially configured fundus camera OcuMet Beacon® (OcuSciences, Ann Arbor, MI). The macula was illuminated using a narrow bandwidth blue light (455 – 470 nm) and fluorescence was recorded using a narrow notch filter to match the peak emission of flavoproteins from 520 to 540 nm. AUROC analysis was used to determine the sensitivity of FPF in discriminating between diseased eyes and healthy eyes. Nonparametric Kruskal-Wallis Tests with post-hoc Mann Whitney U tests with the Holm-Bonferroni correction were performed to assess differences in FPF intensity, FPF heterogeneity, and best corrected visual acuity (BCVA) between the five groups. Spearman rank correlation coefficients were calculated to assess the relationship between FPF and BCVA.ResultsAUROC analysis indicated that FPF intensity is highly sensitive for detecting disease, particularly for exudative AMD subjects (0.989; 95% CI = 0.963 – 1.000, p=3.0 x 107). A significant difference was detected between the FPF intensity, FPF heterogeneity, and BCVA in all four disease states compared to unaffected controls (Kruskal-Wallis Tests, p = 1.06 x 10-8, p = 0.002, p = 5.54 x 10-8, respectively). Compared to healthy controls, FPF intensity values were significantly higher in RVO, DR, exudative AMD, and CSR (p < 0.001, p < 0.001, p < 0.001, and p = 0.001, respectively). Spearman rank correlation coefficient between FPF intensity and BCVA was ρ = 0.595 (p = 9.62 x 10-10).ConclusionsDespite variations in structural retinal findings, FPF was found to be highly sensitive for detecting retinal disease. Significant FPF elevation were seen in all four disease states, with the exudative AMD patients exhibiting the highest FPF values compared to DR, CSR, and RVO subjects. This is consistent with the hypothesis that there is elevated oxidative stress in all of these conditions as previously demonstrated by blood studies. FPF intensity is moderately correlated with the late-in disease-marker BCVA, which suggests that the degree of FPF elevation can be used as a metabolic indicator of disease severity.

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A 6-gene panel as a signature to predict recovery from advanced heart failure using transcriptomic analysis

Cited by 2 publications

References 5 publications

A deformability-based biochip for precise label-free stratification of metastatic subtypes using deep learning

A deformability-based biochip for precise label-free stratification of metastatic subtypes using deep learning

Flavoprotein fluorescence elevation is a marker of mitochondrial oxidative stress in patients with retinal disease

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