Abstract: Interestingly, for prognosis, the significant biomarkers for Gefitinib-treated GBM patients (RTOG 0211) appeared to differ compared to historical, RT and non-Gefitinib-treated GBM patients. In Gefitinib-treated patients, those with higher levels of nuclear pAKT driven by PTEN loss, higher levels of nuclear pMAPK, and lower levels of nuclear pmTOR had significantly worse clinical outcomes. In contrast, in non-Gefitinib-treated patients, patients with PTEN-deficiency, and higher levels of EGFRvIII, total EGFR, IGFR1, NFkB and lower levels of nuclear Survivin appeared to have adverse clinical outcomes, highlighting the treatment-dependency of these biomarkers.

Abstract: A method is described for the reproducible quantification of biomarker expression, including biomarker expression in a tissue sample. Methods and systems are described whereby reproducible scores for biomarker expression are obtained independent of instrument, its location, or operator.

Abstract: Methods of cancer diagnosis and prognosis using biomarkers.

Abstract: A method and system for automatically evaluating quality of a slide-mounted tissue sample includes receiving a digital image of a magnified portion of the slide-mounted tissue sample. At least one quantitative quality indicator is automatically determined for at least one of the samples, and the digital image of the magnified portion of the sample. Each of the quantitative quality indicators is automatically compared to a respective minimum acceptable quality threshold. The quantitative quality indicators and associated quality thresholds are selected for suitability with an automated quantitative immunoassay. Failure of one or more of the quantitative quality indicators to meet its respective minimum acceptable quality threshold suggests that the sample is unsuitable for subsequent automated pathological evaluation.

Abstract: A system and method for automatically and quantitatively determining the optimal dilution of a reagent is provided. In one embodiment of the claimed method, a plurality of dilution sets are received, where each of the dilution sets consist of a different respective dilution value and a respective plurality of immunoassay staining intensity values. A respective dynamic range metric is determining for each of the plurality of dilution sets relative to the respective plurality immunoassay staining intensity values. Having found the respective dynamic range metric, a dilution set having the numerically optimal dynamic range metric is selected and the dilution value of that dilution set is selected as being representative of an optimal dilution level of the reagent for use in a quantitative immunoassay. In one embodiment, a system is provided with a microscope, an image sensor, and processor module configured determine an optimal dilution of a reagent for use in an quantitative immunoassay.

Abstract: The present invention relates generally to improved methods of defining areas or compartments within which biomarker expression is detected and quantified. In particular, the present invention relates to automated methods for delineating marker-defined compartments objectively with minimal operator intervention or decision making. The method provides for precise definition of tissue, cellular or subcellular compartments particularly in histological tissue sections in which to quantitatively analyzing protein expression.

Abstract: Methods and apparatus for standardizing quantitative measurements from a microscope system. The process includes a calibration procedure whereby an image of a calibration slide is obtained through the optics of the microscope system. The calibration slide produces a standard response, which can be used to determine a machine intrinsic factor for the particular system. The machine intrinsic factor can be stored for later reference. In use, images are acquired of a target sample and of the excitation light source. The excitation light source sample is obtained using a calibration instrument configured to sample intensity. The calibration instrument has an associated correction factor to compensate its performance to a universally standardized calibration instrument. The machine intrinsic factor, sampled intensity, and calibration instrument correction factor are usable to compensate a quantitative measurement of the target sample in order to normalize the results for comparison with other microscope systems.

Abstract: Disclosed are methods and compositions for manipulating and detecting nucleic acids. The method generally involves association of a rolling circle replication primer with a cDNA strand. Preferred forms of the methods involve replicating one or more amplification target circles to produce one or more tandem sequence DNAs. Such replication is referred to as rolling circle replication. Preferably, each tandem sequence DNA is coupled to a rolling circle replication primer and the rolling circle replication primer is associated with a cDNA strand. In some embodiments the rolling circle replication primer comprises a capture tag and the association occurs via the capture tag. In some embodiments the cDNA strand is hybridized to a capture probe. Preferably, the cDNA strand comprises an RT primer, wherein the cDNA strand is produced by reverse transcribing a nucleic acid sample with the RT primer.

Abstract: This invention describes novel photoactive ribonucleotides that contain photocrosslinking agents placed at specific internal positions within a ribonucleotide. The invention also provides methods for identifying novel, sequence-specific target molecules, using the photoactive ribonucleotides of the invention, as well as improved nucleic acid hybridization analysis methods.