Abstract: A computer-implemented method for generating a tumor fraction estimate from a DNA sample of a subject is disclosed. The method may include receiving a dataset of methylation sequence reads from the sample of the subject. The method may also include dividing the dataset into a plurality of variants. The method may further include determining methylation states of the plurality of variants. The method may further include filtering the plurality of variants based on a bank of reference sequence reads to generate a filtered subset of variants. The bank may include reads generated from non-cancer samples and biopsy samples of a plurality of tissues of reference individuals. The counts of the methylation states of variants in the filtered subset are determined and input to a model that is trained based on recurrence rates of the variants in the reference sequence reads. The tumor fraction estimate may be generated by the model.

Abstract: Methods and systems for predictive measures of anti-EGFR therapy response in wild type RAS/EGFR+ samples, e.g., histochemical staining methods for staining EGFR, AREG, and EREG, digital analysis of stained slides, and scoring algorithms that allow prediction of a response to anti-EGFR therapies. Analysis of the stained slides and scoring algorithms may include but are not limited to: a percent tumor cell positivity, computerized clustering algorithms, area density (e.g., area of tumor positive for one or more markers over total tumor area), average intensity (e.g., computerized methodology measuring average gray scale pixel intensity), average intensity broken down according to membrane, cytoplasmic, or punctate staining patterns), or any other appropriate parameter or combination of parameters. The methods of the present invention allow for resolving spatial expression patterns of the ligands and the receptor to determine what patterns are predictive for response to anti-EGFR therapies.

Abstract: The present disclosure is directed, among other things, to automated systems and methods for analyzing, storing, and/or retrieving information associated with biological objects having irregular shapes. In some embodiments, the systems and methods partition an input image into a plurality of sub-regions based on localized colors, textures, and/or intensities in the input image, wherein each sub-region represents biologically meaningful data.

Abstract: Techniques for acquiring focused images of a microscope slide are disclosed. During a calibration phase, a “base” focal plane is determined using non-synthetic and/or synthetic auto-focus techniques. Furthermore, offset planes are determined for color channels (or filter bands) and used to generate an auto-focus model. During subsequent scans, the auto-focus model can be used to quickly estimate the focal plane of interest for each color channel (or filter band) rather than re-employing the non-synthetic and/or synthetic auto-focus techniques.

Abstract: The present application provides for systems and methods for detecting and estimating signals corresponding to one or more biomarkers in biological samples stained for the presence of protein and/or nucleic acid biomarkers. On particular aspect is directed to a method of estimating an amount of signal corresponding to at least one biomarker in an image of a biological sample. The method includes detecting isolated spots in a first image, deriving an optical density value of a representative isolated spot based on signal features from the detected isolated spots, estimating a number of predictive spots in signal aggregates in each of a plurality of sub-regions based on the derived optical density value of the representative isolated spot, and storing the estimated number of predictive spots and detected isolated spots in each of the plurality of generated sub-regions in a database.

Abstract: The present disclosure is directed, among other things, to automated systems and methods for analyzing, storing, and/or retrieving information associated with biological objects having irregular shapes. In some embodiments, the systems and methods partition an input image into a plurality of sub-regions based on localized colors, textures, and/or intensities in the input image, wherein each sub-region represents biologically meaningful data.

Abstract: A method for extracting information from a dataset, e.g., a document, includes: receiving the dataset at an information handling device, optionally, extracting, via optical character recognition implemented by a processor of the information handling device, textual information associated with the dataset, and classifying the dataset into one of a plurality of classes. Classifying the dataset may include computing a similarity score for each of the plurality of classes for each of a plurality of window regions of the dataset, calculating a subset of highest similarity scores for each of the plurality of classes for each of the plurality of window regions, determining overall similarity scores for each of the plurality of classes, and classifying the dataset as corresponding to a class with a highest overall similarity score.

Abstract: Techniques for acquiring focused images of a microscope slide are disclosed. During a calibration phase, a “base” focal plane is determined using non-synthetic and/or synthetic auto-focus techniques. Furthermore, offset planes are determined for color channels (or filter bands) and used to generate an auto-focus model. During subsequent scans, the auto-focus model can be used to quickly estimate the focal plane of interest for each color channel (or filter band) rather than re-employing the non-synthetic and/or synthetic auto-focus techniques.

Abstract: The present disclosure is directed, among other things, to automated systems and methods for analyzing, storing, and/or retrieving information associated with biological objects having irregular shapes. In some embodiments, the systems and methods partition an input image into a plurality of sub-regions based on localized colors, textures, and/or intensities in the input image, wherein each sub-region represents biologically meaningful data.

Abstract: Immune context scores are calculated for tumor tissue samples using continuous scoring functions. Feature metrics for at least one immune cell marker are calculated for a region or regions of interest, the feature metrics including at least a quantitative measure of human CD3 or total lymphocyte counts. A continuous scoring function is then applied to a feature vector including the feature metric and at least one additional metric related to an immunological biomarker, the output of which is an immune context score. The immune context score may then be plotted as a function of a diagnostic or treatment metric, such as a prognostic metric (e.g. overall survival, disease-specific survival, progression-free survival) or a predictive metric (e.g. likelihood of response to a particular treatment course). The immune context score may then be incorporated into diagnostic and/or treatment decisions.

Abstract: The subject disclosure presents systems and methods for automatically selecting meaningful regions on a whole-slide image and performing quality control on the resulting collection of FOVs. Density maps may be generated quantifying the local density of detection results. The heat maps as well as combinations of maps (such as a local sum, ratio, etc.) may be provided as input into an automated FOV selection operation. The selection operation may select regions of each heat map that represent extreme and average representative regions, based on one or more rules. One or more rules may be defined in order to generate the list of candidate FOVs. The rules may generally be formulated such that FOVs chosen for quality control are the ones that require the most scrutiny and will benefit the most from an assessment by an expert observer.

Abstract: The present application provides for systems and methods for detecting and estimating signals corresponding to one or more biomarkers in biological samples stained for the presence of protein and/or nucleic acid biomarkers. On particular aspect is directed to a method of estimating an amount of signal corresponding to at least one biomarker in an image of a biological sample. The method includes detecting isolated spots in a first image, deriving an optical density value of a representative isolated spot based on signal features from the detected isolated spots, estimating a number of predictive spots in signal aggregates in each of a plurality of sub-regions based on the derived optical density value of the representative isolated spot, and storing the estimated number of predictive spots and detected isolated spots in each of the plurality of generated sub-regions in a database.

Abstract: The subject disclosure presents systems and methods for automatically selecting meaningful regions on a whole-slide image and performing quality control on the resulting collection of FOVs. Density maps may be generated quantifying the local density of detection results. The heat maps as well as combinations of maps (such as a local sum, ratio, etc.) may be provided as input into an automated FOV selection operation. The selection operation may select regions of each heat map that represent extreme and average representative regions, based on one or more rules. One or more rules may be defined in order to generate the list of candidate FOVs. The rules may generally be formulated such that FOVs chosen for quality control are the ones that require the most scrutiny and will benefit the most from an assessment by an expert observer.

Abstract: The present description provides a cancer assay panel for targeted detection of cancer-specific methylation patterns. Further provided herein includes methods of designing, making, and using the cancer assay panel to detect cancer and particular types of cancer.

Abstract: The present description provides a cancer assay panel for targeted detection of cancer-specific methylation patterns. Further provided herein includes methods of designing, making, and using the cancer assay panel for detection of cancer tissue of origin (e.g., types of cancer).

Abstract: The present description provides a cancer assay panel for targeted detection of cancer-specific methylation patterns. Further provided herein includes methods of designing, making, and using the cancer assay panel to detect cancer and particular types of cancer.

Abstract: The present description provides a hematological disorder (HD) assay panel for targeted detection of methylation patterns or variants specific to various hematological disorders, such as clonal hematopoiesis of indeterminate potential (CHIP) and blood cancers, such as leukemia, lymphoid neoplasms (e.g. lymphoma), multiple myeloma, and myeloid neoplasm. Further provided herein includes methods of designing, making, and using the HD assay panel for detection of various hematological disorders.

Abstract: Immune context scores are calculated for tumor tissue samples using continuous scoring functions. Feature metrics for at least one immune cell marker are calculated for a region or regions of interest, the feature metrics including at least a quantitative measure of human CD3 or total lymphocyte counts. A continuous scoring function is then applied to a feature vector including the feature metric and at least one additional metric related to an immunological biomarker, the output of which is an immune context score. The immune context score may then be plotted as a function of a diagnostic or treatment metric, such as a prognostic metric (e.g. overall survival, disease-specific survival, progression-free survival) or a predictive metric (e.g. likelihood of response to a particular treatment course). The immune context score may then be incorporated into diagnostic and/or treatment decisions.

Abstract: Systems and methods disclosed herein describe a platform that automatically creates and executes a scoring guide for use in anatomical pathology. The platform can employ a fully-automated workflow for clustering the biological objects of interest and for providing cell-by-cell read-outs of heterogeneous tumor biomarkers based on their stain appearance. The platform can include a module for automatically creating and storing a scoring guide in a training database based on training digital images (240, 250), and an object classification module that executes the scoring guide when presented with new digital images to be scored pursuant to the scoring guide (299).

Abstract: Systems and methods described herein include detecting a presence or absence of HPV in a biological sample having cell-free nucleic acids from a subject and potentially cell-free nucleic acids from an HPV strain. Based on a detection of HPV viral nucleic acids in the biological sample, an HPV-based multiclass classifier that predicts a score for each HPV-associated cancer type is applied. The HPV-based multiclass classifier is trained on a training set of HPV-positive cancer samples. An HPV-associated cancer associated with the biological sample is determined based on the scores predicted by the HPV multiclass classifier.