Abstract: A method of in situ immunohistochemical analysis of a biological sample is provided. The method allows for the multiplex and simultaneous detection of multiple antigens, including multiple nuclear antigens, in a tissue sample.

Abstract: The present invention relates to a method for detecting one or more nascent RNAs in a tissue sample using FISH. In the method, a plurality of probes (8 to 82) may be used to detect a single species of nascent RNA. Further, a plurality of nascent RNA species may be detected simultaneously using between 8 and 82 probes for each nascent RNA. The invention comprises, in addition, methods of preparing a sample for nascent RNA detection by reducing autofluorescence of the tissue sample. These techniques may be synergistically combined to achieve significantly improved results.

Abstract: A method of producing a model for use in predicting time to an event includes obtaining multi-dimensional, non-linear vectors of information indicative of status of multiple test subjects, at least one of the vectors being right-censored, lacking an indication of a time of occurrence of the event with respect to the corresponding test subject, and performing regression using the vectors of information to produce a kernel-based model to provide an output value related to a prediction of time to the event based upon at least some of the information contained in the vectors of information, where for each vector comprising right-censored data, a censored-data penalty function is used to affect the regression, the censored-data penalty function being different than a non-censored-data penalty function used for each vector comprising non-censored data.

Abstract: This present invention systems and methods of accessing/monitoring the responsiveness of a breast cancer to a therapeutic compound.

Abstract: Methods and systems are provided for feature selection in machine learning, in which the features selected for inclusion in a prediction rule are selected based on statistical metric(s) of feature contribution and/or model fitness.

Abstract: Clinical information, molecular information and/or computer-generated morphometric information is used in a predictive model for predicting the occurrence of a medical condition. In an embodiment, a model predicts whether a patient is likely to have a favorable pathological stage of prostate cancer, where the model is based on features including one or more (e.g., all) of preoperative PSA, Gleason Score, a measurement of expression of androgen receptor (AR) in epithelial and stromal nuclei and/or a measurement of expression of Ki67-positive epithelial nuclei, a morphometric measurement of a ratio of area of epithelial nuclei outside gland units to area of epithelial nuclei within gland units, and a morphometric measurement of area of epithelial nuclei distributed away from gland units. In some embodiments, quantitative measurements of protein expression in cell lines are utilized to objectively assess assay (e.g.

Abstract: Systems and methods are provided for automated diagnosis and grading of tissue images based on morphometric data extracted from the images by a computer. The morphometric data may include image-level morphometric data such as fractal dimension data, fractal code data, wavelet data, and/or color channel histogram data. The morphometric data may also include object-level morphometric data such as color, structural, and/or textural properties of segmented image objects (e.g., stroma, nuclei, red blood cells, etc.).

Abstract: Clinical information, molecular information and/or computer-generated morphometric information is used in a predictive model for predicting the occurrence of a medical condition. In an embodiment, a model predicts risk of prostate cancer progression in a patient, where the model is based on features including one or more (e.g., all) of preoperative PSA, dominant Gleason Grade, Gleason Score, at least one of a measurement of expression of AR in epithelial and stromal nuclei and a measurement of expression of Ki67-positive epithelial nuclei, a morphometric measurement of average edge length in the minimum spanning tree (MST) of epithelial nuclei, and a morphometric measurement of area of non-lumen associated epithelial cells relative to total tumor area. In some embodiments, the morphometric information is based on image analysis of tissue subject to multiplex immunofluorescence and may include characteristic(s) of a minimum spanning tree (MST) and/or a fractal dimension observed in the images.

Abstract: Embodiments of the present invention are directed to methods and systems for training a neural network having weighted connections for classification of data, as well as embodiments corresponding to the use of such a neural network for the classification of data, including, for example, prediction of an event (e.g., disease). The method may include inputting input training data into the neural network, processing, by the neural network, the input training data to produce an output, determining an error between the output and a desired output corresponding to the input training data, rating the performance neural network using an objective function, wherein the objective function comprises a function C substantially in accordance with an approximation of the concordance index and adapting the weighted connections of the neural network based upon results of the objective function.

Abstract: Methods and systems are provided that use clinical information, molecular information and computer-generated morphometric information in a predictive model for predicting the occurrence (e.g., recurrence) of a medical condition, for example, cancer. In an embodiment, a model that predicts prostate cancer recurrence is provided, where the model is based on features including one or more (e.g., all) of biopsy Gleason score, seminal vesicle invasion, extracapsular extension, preoperative PSA, dominant prostatectomy Gleason grade, the relative area of AR+ epithelial nuclei, a morphometric measurement of epithelial nuclei, and a morphometric measurement of epithelial cytoplasm. In another embodiment, a model that predicts clinical failure post-prostatectomy is provided, wherein the model is based on features including one or more (e.g.

Abstract: A method of producing a model for use in predicting time to an event includes obtaining multi-dimensional, non-linear vectors of information indicative of status of multiple test subjects, at least one of the vectors being right-censored, lacking an indication of a time of occurrence of the event with respect to the corresponding test subject, and performing regression using the vectors of information to produce a kernel-based model to provide an output value related to a prediction of time to the event based upon at least some of the information contained in the vectors of information, where for each vector comprising right-censored data, a censored-data penalty function is used to affect the regression, the censored-data penalty function being different than a non-censored-data penalty function used for each vector comprising non-censored data.

Abstract: Embodiments of the present invention are directed to quantitative analysis of tissues enabling the measurement of objects and parameters of objects found in images of tissues including perimeter, area, and other metrics of such objects. Measurement results may be input into a relational database where they can be statistically analyzed and compared across studies. The measurement results may be used to create a pathological tissue map of a tissue image, to allow a pathologist to determine a pathological condition of the imaged tissue more quickly.

Abstract: Methods and systems are provided for feature selection in machine learning, in which the features selected for inclusion in a prediction rule are selected based on statistical metric(s) of feature contribution and/or model fitness.

Abstract: A method, a system, and a computer-readable medium for predicting a risk in a survival analysis for a plurality of individuals characterized by at least one predictor are disclosed. A method for estimating risk order of an individual, given information about a set of individuals, characterized by one or many predictors, and provided that direction of association between each predictor and the risk order is known, comprising the step of comparing the individual with each individual within the set of individuals, and estimating risk of individual based on set comparisons.

Abstract: A method of producing a model for use in predicting time to an event includes obtaining multi-dimensional, non-linear vectors of information indicative of status of multiple test subjects, at least one of the vectors being right-censored, lacking an indication of a time of occurrence of the event with respect to the corresponding test subject, and performing regression using the vectors of information to produce a kernel-based model to provide an output value related to a prediction of time to the event based upon at least some of the information contained in the vectors of information, where for each vector comprising right-censored data, a censored-data penalty function is used to affect the regression, the censored-data penalty function being different than a non-censored-data penalty function used for each vector comprising non-censored data.

Abstract: Embodiments of the present invention are directed to quantitative analysis of tissues enabling the measurement of objects and parameters of objects found in images of tissues including perimeter, area, and other metrics of such objects. Measurement results may be input into a relational database where they can be statistically analyzed and compared across studies. The measurement results may be used to create a pathological tissue map of a tissue image, to allow a pathologist to determine a pathological condition of the imaged tissue more quickly.

Abstract: Methods and systems are provided that use clinical information, molecular information and computer-generated morphometric information in a predictive model for predicting the occurrence (e.g., recurrence) of a medical condition, for example, cancer.

Abstract: Embodiments of the present invention are directed to methods and systems for training a neural network having weighted connections for classification of data, as well as embodiments corresponding to the use of such a neural network for the classification of data, including, for example, prediction of an event (e.g., disease). The method may include inputting input training data into the neural network, processing, by the neural network, the input training data to produce an output, determining an error between the output and a desired output corresponding to the input training data, rating the performance neural network using an objective function, wherein the objective function comprises a function C substantially in accordance with an approximation of the concordance index and adapting the weighted connections of the neural network based upon results of the objective function.

Abstract: Methods and systems are provided that use clinical information, molecular information and computer-generated morphometric information in a predictive model for predicting the occurrence (e.g., recurrence) of a medical condition, for example, cancer. In an embodiment, a model that predicts prostate cancer recurrence is provided, where the model is based on features including seminal vesicle involvement, surgical margin involvement, lymph node status, androgen receptor (AR) staining index of tumor, a morphometric measurement of epithelial nuclei, and at least one morphometric measurement of stroma.

Abstract: Embodiments of the present invention are directed to methods and systems for training a neural network having weighted connections for classification of data, as well as embodiments corresponding to the use of such a neural network for the classification of data, including, for example, prediction of an event (e.g., disease). The method may include inputting input training data into the neural network, processing, by the neural network, the input training data to produce an output, determining an error between the output and a desired output corresponding to the input training data, rating the performance neural network using an objective function, wherein the objective function comprises a function C substantially in accordance with an approximation of the concordance index and adapting the weighted connections of the neural network based upon results of the objective function.