ABSTRACT
Discovering states of genetic expression that are true to a high degree of certainty is likely to predict gene function behind biological phenotypes. The states of expression (up- or down-regulated) of 19200 cDNAs in 10 meningiomas are compared with normal brain by an algorithm that detects only 1 false measurement per 192000; 364 genes are discovered. The expression data accurately predict activation of signaling pathways and link gene function to specific phenotypes. Meningiomas appear to acquire aberrant phenotypes by disturbing the balanced expression of molecules that promote opposing functions. The findings expose interconnected genes and propose a role of genomic expression discovery in functional genomics of living systems.
Subject(s)
Gene Expression Profiling/methods , Meningioma/genetics , RNA, Neoplasm/analysis , Algorithms , Brain/metabolism , Brain/pathology , Case-Control Studies , Gene Expression Regulation , Humans , Oligonucleotide Array Sequence Analysis , Phenotype , Signal TransductionABSTRACT
The microarray array experimental system generates noisy data that require validation by other experimental methods for measuring gene expression. Here we present an algebraic modeling of noise that extracts expression measurements true to a high degree of confidence. This work profiles the expression of 19 200 cDNAs in 35 human gliomas; the experiments are designed to generate four replicate spots/gene with switching of probes. The validity of the extracted measurements is confirmed by: (1) cluster analysis that generates a molecular classification differentiating glioblastoma from lower-grade tumors and radiation necrosis; (2) By what other investigators have reported in gliomas using paradigms for assaying molecular expression other than gene profiling; and (3) Real-time RT-PCR. The results yield a genetic analysis of gliomas and identify classes of genetic expression that link novel genes to the biology of gliomas.
Subject(s)
Gene Expression , Glioma/genetics , Models, Theoretical , Brain Neoplasms/genetics , Gene Expression Profiling , Glioblastoma/genetics , Humans , Multigene Family , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Our experience in treating 10 patients with intractable pain with paraplegia employing percutaneous epidural or dorsal column stimulation is presented. Initial and long-term results in this group are contrasted with those of 9 patients with intractable post-amputation or post-traumatic neuroma pain. The successful results of neurostimulation treatment of peripheral nerve pain contasts with the disappointing results in the treatment of paraplegic pain.
