scholarly journals Personalized Survival Prediction of Patients With Acute Myeloblastic Leukemia Using Gene Expression Profiling

2021 ◽  
Vol 11 ◽  
Author(s):  
Adrián Mosquera Orgueira ◽  
Andrés Peleteiro Raíndo ◽  
Miguel Cid López ◽  
José Ángel Díaz Arias ◽  
Marta Sonia González Pérez ◽  
...  

Acute Myeloid Leukemia (AML) is a heterogeneous neoplasm characterized by cytogenetic and molecular alterations that drive patient prognosis. Currently established risk stratification guidelines show a moderate predictive accuracy, and newer tools that integrate multiple molecular variables have proven to provide better results. In this report, we aimed to create a new machine learning model of AML survival using gene expression data. We used gene expression data from two publicly available cohorts in order to create and validate a random forest predictor of survival, which we named ST-123. The most important variables in the model were age and the expression of KDM5B and LAPTM4B, two genes previously associated with the biology and prognostication of myeloid neoplasms. This classifier achieved high concordance indexes in the training and validation sets (0.7228 and 0.6988, respectively), and predictions were particularly accurate in patients at the highest risk of death. Additionally, ST-123 provided significant prognostic improvements in patients with high-risk mutations. Our results indicate that survival of patients with AML can be predicted to a great extent by applying machine learning tools to transcriptomic data, and that such predictions are particularly precise among patients with high-risk mutations.

Leukemia ◽  
2021 ◽  
Author(s):  
Adrián Mosquera Orgueira ◽  
Marta Sonia González Pérez ◽  
José Ángel Díaz Arias ◽  
Beatriz Antelo Rodríguez ◽  
Natalia Alonso Vence ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Liye Zhou ◽  
Zhifei Guo ◽  
Bijue Wang ◽  
Yongqing Wu ◽  
Zhi Li ◽  
...  

Heart failure with preserved ejection fraction (HFpEF) has become a major health issue because of its high mortality, high heterogeneity, and poor prognosis. Using genomic data to classify patients into different risk groups is a promising method to facilitate the identification of high-risk groups for further precision treatment. Here, we applied six machine learning models, namely kernel partial least squares with the genetic algorithm (GA-KPLS), the least absolute shrinkage and selection operator (LASSO), random forest, ridge regression, support vector machine, and the conventional logistic regression model, to predict HFpEF risk and to identify subgroups at high risk of death based on gene expression data. The model performance was evaluated using various criteria. Our analysis was focused on 149 HFpEF patients from the Framingham Heart Study cohort who were classified into good-outcome and poor-outcome groups based on their 3-year survival outcome. The results showed that the GA-KPLS model exhibited the best performance in predicting patient risk. We further identified 116 differentially expressed genes (DEGs) between the two groups, thus providing novel therapeutic targets for HFpEF. Additionally, the DEGs were enriched in Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways related to HFpEF. The GA-KPLS-based HFpEF model is a powerful method for risk stratification of 3-year mortality in HFpEF patients.


Cell Cycle ◽  
2018 ◽  
Vol 17 (4) ◽  
pp. 486-491 ◽  
Author(s):  
Nicolas Borisov ◽  
Victor Tkachev ◽  
Maria Suntsova ◽  
Olga Kovalchuk ◽  
Alex Zhavoronkov ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Shuhei Kaneko ◽  
Akihiro Hirakawa ◽  
Chikuma Hamada

In the past decade, researchers in oncology have sought to develop survival prediction models using gene expression data. The least absolute shrinkage and selection operator (lasso) has been widely used to select genes that truly correlated with a patient’s survival. The lasso selects genes for prediction by shrinking a large number of coefficients of the candidate genes towards zero based on a tuning parameter that is often determined by a cross-validation (CV). However, this method can pass over (or fail to identify) true positive genes (i.e., it identifies false negatives) in certain instances, because the lasso tends to favor the development of a simple prediction model. Here, we attempt to monitor the identification of false negatives by developing a method for estimating the number of true positive (TP) genes for a series of values of a tuning parameter that assumes a mixture distribution for the lasso estimates. Using our developed method, we performed a simulation study to examine its precision in estimating the number of TP genes. Additionally, we applied our method to a real gene expression dataset and found that it was able to identify genes correlated with survival that a CV method was unable to detect.


2020 ◽  
Vol 21 (S14) ◽  
Author(s):  
Evan A. Clayton ◽  
Toyya A. Pujol ◽  
John F. McDonald ◽  
Peng Qiu

Abstract Background Machine learning has been utilized to predict cancer drug response from multi-omics data generated from sensitivities of cancer cell lines to different therapeutic compounds. Here, we build machine learning models using gene expression data from patients’ primary tumor tissues to predict whether a patient will respond positively or negatively to two chemotherapeutics: 5-Fluorouracil and Gemcitabine. Results We focused on 5-Fluorouracil and Gemcitabine because based on our exclusion criteria, they provide the largest numbers of patients within TCGA. Normalized gene expression data were clustered and used as the input features for the study. We used matching clinical trial data to ascertain the response of these patients via multiple classification methods. Multiple clustering and classification methods were compared for prediction accuracy of drug response. Clara and random forest were found to be the best clustering and classification methods, respectively. The results show our models predict with up to 86% accuracy; despite the study’s limitation of sample size. We also found the genes most informative for predicting drug response were enriched in well-known cancer signaling pathways and highlighted their potential significance in chemotherapy prognosis. Conclusions Primary tumor gene expression is a good predictor of cancer drug response. Investment in larger datasets containing both patient gene expression and drug response is needed to support future work of machine learning models. Ultimately, such predictive models may aid oncologists with making critical treatment decisions.


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