Kernel Fusion Method for Detecting Cancer Subtypes via Selecting Relevant Expression Data
FRONTIERS IN GENETICS
Authors: Li, Shuhao; Jiang, Limin; Tang, Jijun; Gao, Nan; Guo, Fei
Abstract
Recently, cancer has been characterized as a heterogeneous disease composed of many different subtypes. Early diagnosis of cancer subtypes is an important study of cancer research, which can be of tremendous help to patients after treatment. In this paper, we first extract a novel dataset, which contains gene expression, miRNA expression, and isoform expression of five cancers from The Cancer Genome Atlas (TCGA). Next, to avoid the effect of noise existing in 60, 483 genes, we select a small number of genes by using LASSO that employs gene expression and survival time of patients. Then, we construct one similarity kernel for each expression data by using Chebyshev distance. And also, We used SKF to fused the three similarity matrix composed of gene, Iso, and miRNA, and finally clustered the fused similarity matrix with spectral clustering. In the experimental results, our method has betterP-value in the Cox model than other methods on 10 cancer data from Jiang Dataset and Novel Dataset. We have drawn different survival curves for different cancers and found that some genes play a key role in cancer. For breast cancer, we find out that HSPA2A, RNASE1, CLIC6, and IFITM1 are highly expressed in some specific groups. For lung cancer, we ensure that C4BPA, SESN3, and IRS1 are highly expressed in some specific groups. The code and all supporting data files are available from.
Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis
THERAPEUTIC ADVANCES IN CHRONIC DISEASE
Authors: Blanco, Francisco J.; Camacho-Encina, Maria; Gonzalez-Rodriguez, Lucia; Rego-Perez, Ignacio; Mateos, Jesus; Fernandez-Puente, Patricia; Lourido, Lucia; Rocha, Beatriz; Picchi, Florencia; Silva-Diaz, Maria T.; Herrero, Marta; Martinez, Helena; Verges, Josep; Ruiz-Romero, Cristina; Calamia, Valentina
Abstract
Background: In the present study, we explored potential protein biomarkers useful to predict the therapeutic response of knee osteoarthritis (KOA) patients treated with pharmaceutical grade Chondroitin sulfate/Glucosamine hydrochloride (CS+GH; Droglican, Bioiberica), in order to optimize therapeutic outcomes. Methods: A shotgun proteomic analysis by iTRAQ labelling and liquid chromatography-mass spectrometry (LC-MS/MS) was performed using sera from 40 patients enrolled in the Multicentre Osteoarthritis interVEntion trial with Sysadoa (MOVES). The panel of proteins potentially useful to predict KOA patient's response was clinically validated in the whole MOVES cohort at baseline (n = 506) using commercially available enzyme-linked immunosorbent assays kits. Logistic regression models and receiver-operating-characteristics (ROC) curves were used to analyze the contribution of these proteins to our prediction models of symptomatic drug response in KOA. Results: In the discovery phase of the study, a panel of six putative predictive biomarkers of response to CS+GH (APOA2, APOA4, APOH, ITIH1, C4BPa and ORM2) were identified by shotgun proteomics. Data are available via ProteomeXchange with identifier PXD012444. In the verification phase, the panel was verified in a larger set of KOA patients (n = 262). Finally, ITIH1 and ORM2 were qualified by a blind test in the whole MOVES cohort at baseline. The combination of these biomarkers with clinical variables predict the patients' response to CS+GH with a specificity of 79.5% and a sensitivity of 77.1%. Conclusions: Combining clinical and analytical parameters, we identified one biomarker that could accurately predict KOA patients' response to CS+GH treatment. Its use would allow an increase in response rates and safety for the patients suffering KOA.