PubMed Health⌕ Search

Biomedical subjects

Sara Alvarez de Andrés

Publications and source records attributed to Sara Alvarez de Andrés.

3 recordsLinked to original sources

Gene selection and classification of microarray data using random forest.

BACKGROUND: Selection of relevant genes for sample classification is a common task in most gene expression studies, where researchers try to identify the smallest possible set of genes that can still achieve good predictive performance (for instance, for future use with diagnostic purposes in clinical practice). Many gene selection approaches use univariate (gene-by-gene) rankings of gene relevance and arbitrary thresholds to select the number of genes, can only be applied to two-class problems, and use gene selection ranking criteria unrelated to the classification algorithm. In contrast, random forest is a classification algorithm well suited for microarray data: it shows excellent performance even when most predictive variables are noise, can be used when the number of variables is much larger than the number of observations and in problems involving more than two classes, and returns measures of variable importance. Thus, it is important to understand the performance of random forest with microarray data and its possible use for gene selection. RESULTS: We investigate the use of random forest for classification of microarray data (including multi-class problems) and propose a new method of gene selection in classification problems based on random forest. Using simulated and nine microarray data sets we show that random forest has comparable performance to other classification methods, including DLDA, KNN, and SVM, and that the new gene selection procedure yields very small sets of genes (often smaller than alternative methods) while preserving predictive accuracy. CONCLUSION: Because of its performance and features, random forest and gene selection using random forest should probably become part of the "standard tool-box" of methods for class prediction and gene selection with microarray data.

Algorithms↗

Analysis of myelodysplastic syndromes with complex karyotypes by high-resolution comparative genomic hybridization and subtelomeric CGH array.

Molecular cytogenetic techniques enabled us to clarify numerical and structural alterations previously detected by conventional cytogenetic techniques in 37 patients who had myelodysplastic syndromes with complex karyotypes. Using high-resolution comparative genomic hybridization (HR-CGH), we found the most recurrent alterations to be deletion of 5q (70%), 18q (35%), 7q (32%), 11q (30%), and 20q (24%), gain of 11q (35%) and 8q (24%), and trisomy of chromosome 8 (19%). Furthermore, in 35% of the patients, 20 amplifications were identified. These amplifications were shown by FISH to involve some genes previously described as amplified in hematological malignancies, such as ERBB2, MLL, and RUNX1. In addition, two other genes, BCL6 and BCL2, which are classically related to apoptosis and non-Hodgkin lymphoma, were shown for the first time to be involved in amplification. Genomic alterations involving different subtelomeric regions with losses in 4p16, 5p15.3, 6q27, 18p11.3, and 18q23 and gains in 1p36.3 and 19p13.3 were detected by HR-CGH. Array CGH analysis of the subtelomeric regions in some samples was able to confirm a number of these alterations and found some additional alterations not detected by conventional CGH.

Aged↗

Molecular cytogenetic characterization of rhabdomyosarcoma cell lines.

Alveolar rhabdomyosarcomas (ARMS) are soft-tissue tumors that are genetically characterized by the presence of reciprocal translocations that generate the fusion gene PAX3-FOXO1A or PAX7-FOXO1A. For the study of the biologic consequences of such rearrangements, several cell lines have been generated. However, established cell lines accumulate chromosome and genetic aberrations that make it difficult to draw significant conclusions. We have applied a set of techniques that includes spectral karyotyping, fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), and microarray CGH, to the most commonly used cell lines carrying the two fusion genes that are present in ARMS. We have identified the bacterial artificial chromosomes that cover the breakpoints at genes PAX3, PAX7, and FOXO1A, which can be used as FISH probes for the translocations. The RH30 cell line, positive for the PAX3-FOXO1A fusion gene, was found to be highly complex: wide range of chromosome number, more than 50 chromosome rearrangements, amplification of the hybrid gene, 24 DNA changes detected by conventional CGH, and 21 gene copy changes detected by microarray CGH (including several high-level amplifications). RMZ-RC2 cell line, positive for the PAX7-FOXO1A, was in the near-tetraploid range with only nonclonal structural rearrangements, amplification of the hybrid gene, 24 DNA changes by CGH, and 8 gene copy changes, confirming the previously reported high-level amplification of MYCN.

Cell Line, Tumor↗