17 research outputs found
Compositionality, stochasticity and cooperativity in dynamic models of gene regulation
We present an approach for constructing dynamic models for the simulation of
gene regulatory networks from simple computational elements. Each element is
called a ``gene gate'' and defines an input/output-relationship corresponding
to the binding and production of transcription factors. The proposed reaction
kinetics of the gene gates can be mapped onto stochastic processes and the
standard ode-description. While the ode-approach requires fixing the system's
topology before its correct implementation, expressing them in stochastic
pi-calculus leads to a fully compositional scheme: network elements become
autonomous and only the input/output relationships fix their wiring. The
modularity of our approach allows to pass easily from a basic first-level
description to refined models which capture more details of the biological
system. As an illustrative application we present the stochastic repressilator,
an artificial cellular clock, which oscillates readily without any cooperative
effects.Comment: 15 pages, 8 figures. Accepted by the HFSP journal (13/09/07
O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction
Background: The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP. Methods A computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance. Results Of 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value. Conclusions Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably