Disease modelling using evolved discriminate function

Precocious diagnosis increases the survival time and patient quality of life. It is a binary classification, exhaustively studied in the literature. This paper innovates proposing the application of genetic programming to obtain a discriminate function. This function contains the disease dynamics used to classify the patients with as little false negative diagnosis as possible. If its value is greater than zero then it means that the patient is ill, otherwise healthy. A graphical representation is proposed to show the influence of each dataset attribute in the discriminate function. The experiment deals with Breast Cancer and Thrombosis & Collagen diseases diagnosis. The main conclusion is that the discriminate function is able to classify the patient using numerical clinical data, and the graphical representation displays patterns that allow understanding of the model

Disease modeling using Evolved Discriminate Function

Precocious diagnosis increases the survival time and patient quality of life. It is a binary classification, exhaustively studied in the literature. This paper innovates proposing the application of genetic programming to obtain a discriminate function. This function contains the disease dynamics used to classify the patients with as little false negative diagnosis as possible. If its value is greater than zero then it means that the patient is ill, otherwise healthy. A graphical representation is proposed to show the influence of each dataset attribute in the discriminate function. The experiment deals with Breast Cancer and Thrombosis & Collagen diseases diagnosis. The main conclusion is that the discriminate function is able to classify the patient using numerical clinical data, and the graphical representation displays patterns that allow understanding of the model

Detecting high-order interactions of single nucleotide polymorphisms using genetic programming

Motivation: Not individual single nucleotide polymorphisms (SNPs), but high-order interactions of SNPs are assumed to be responsible for complex diseases such as cancer. Therefore, one of the major goals of genetic association studies concerned with such genotype data is the identification of these high-order interactions. This search is additionally impeded by the fact that these interactions often are only explanatory for a relatively small subgroup of patients. Most of the feature selection methods proposed in the literature, unfortunately, fail at this task, since they can either only identify individual variables or interactions of a low order, or try to find rules that are explanatory for a high percentage of the observations. In this paper, we present a procedure based on genetic programming and multi-valued logic that enables the identification of high-order interactions of categorical variables such as SNPs. This method called GPAS (Genetic Programming for Association Studies) cannot only be used for feature selection, but can also be employed for discrimination. Results: In an application to the genotype data from the GENICA study, an association study concerned with sporadic breast cancer, GPAS is able to identify high-order interactions of SNPs leading to a considerably increased breast cancer risk for different subsets of patients that are not found by other feature selection methods. As an application to a subset of the HapMap data shows, GPAS is not restricted to association studies comprising several ten SNPs, but can also be employed to analyze whole-genome data. --

Spatiotemporal switching signals for cancer stem cell activation in pediatric origins of adulthood cancer: Towards a watch-and-wait lifetime strategy for cancer treatment.

Pediatric origin of cancer stem cell hypothesis holds great promise and potential in adult cancer treatment, however; the road to innovation is full of obstacles as there are plenty of questions left unanswered. First, the key question is to characterize the nature of such stem cells (concept). Second, the quantitative imaging of pediatric stem cells should be implemented (technology). Conceptually, pediatric stem cell origins of adult cancer are based on the notion that plasticity in early life developmental programming evolves local environments to cancer. Technologically, such imaging in children is lacking as all imaging is designed for adult patients. We postulate that the need for quantitative imaging to measure space-time changes of plasticity in early life developmental programming in children may trigger research and development of the imaging technology. Such quantitative imaging of pediatric origin of adulthood cancer will help develop a spatiotemporal monitoring system to determine cancer initiation and progression. Clinical validation of such speculative hypothesis-that cancer originates in a pediatric environment-will help implement a wait-and-watch strategy for cancer treatment

A statistical approach for array CGH data analysis

BACKGROUND: Microarray-CGH experiments are used to detect and map chromosomal imbalances, by hybridizing targets of genomic DNA from a test and a reference sample to sequences immobilized on a slide. These probes are genomic DNA sequences (BACs) that are mapped on the genome. The signal has a spatial coherence that can be handled by specific statistical tools. Segmentation methods seem to be a natural framework for this purpose. A CGH profile can be viewed as a succession of segments that represent homogeneous regions in the genome whose BACs share the same relative copy number on average. We model a CGH profile by a random Gaussian process whose distribution parameters are affected by abrupt changes at unknown coordinates. Two major problems arise : to determine which parameters are affected by the abrupt changes (the mean and the variance, or the mean only), and the selection of the number of segments in the profile. RESULTS: We demonstrate that existing methods for estimating the number of segments are not well adapted in the case of array CGH data, and we propose an adaptive criterion that detects previously mapped chromosomal aberrations. The performances of this method are discussed based on simulations and publicly available data sets. Then we discuss the choice of modeling for array CGH data and show that the model with a homogeneous variance is adapted to this context. CONCLUSIONS: Array CGH data analysis is an emerging field that needs appropriate statistical tools. Process segmentation and model selection provide a theoretical framework that allows precise biological interpretations. Adaptive methods for model selection give promising results concerning the estimation of the number of altered regions on the genome