Method For Automated Tissue Analysis
AssigneeCernostics, Inc.
InventorsAlbert H. Gough, Kenneth A. Giuliano, D. Lansing Taylor
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Abstract
The invention provides an improved method for identifying and interpreting tissue specimens and/or cells derived from tissue specimens. A panel of cell-based reagents provides a number of readouts of cellular states or biomarkers that together define a profile of a diversity of cellular states or biomarkers in a tissue specimen representing the ‘systems” nature of biology. This cellular profile is interpreted using informatics tools, to identify similarities between specimens, in vivo medical conditions, and suggest options for treating medical conditions.
Claims21
A method for producing a cellular systems biology profile of one or more tissue samples comprising:
- a) obtaining at least two sections from one or more tissue samples;
- b) labeling at least one section with a histological stain, thereby producing a histologically stained section;
- c) labeling at least one section with a panel of fluorescently labeled reagents, thereby producing a fluorescently labeled section, wherein each fluorescently labeled reagent is specific for a biomarker, and wherein the panel of fluorescently labeled reagents detects at least four different biomarkers, and wherein the detection of a biomarker is a read-out of one or more features of a cellular systems biology profile;
- d) imaging the histologically stained section with at least a first optical mode, wherein the imaging produces a first set of data;
- e) imaging the fluorescently labeled section with at least a second optical mode, wherein the imaging produces a second set of data;
- f) analyzing the first set of data and the second set of data to identify five or more features, wherein at least one feature is identified in each of the first set of data and the second set of data, and wherein the combination of the five or more features generates a cellular systems biology profile of the one or more tissue samples,
- wherein at least the steps of e) and f) are automated, thereby providing a method for producing a cellular systems biology profile of the one or more tissue samples.
A method for producing a cellular systems biology profile of one or more tissue samples comprising:
- a) obtaining at least one section from one or more tissue samples;
- b) labeling the at least one section with a panel of fluorescently labeled reagents, thereby producing a fluorescently labeled section, wherein each fluorescently labeled reagent is specific for a biomarker, and wherein the panel of fluorescently labeled reagents detects at least four different biomarkers, and wherein the detection of a biomarker is a read-out of one or more features of a cellular systems biology profile;
- c) imaging the fluorescently labeled section with at least a first optical mode, wherein the imaging produces a first set of data;
- d) analyzing the first set of data to identify five or more features, wherein at least one feature is identified in the first set of data, and wherein the combination of the five or more features is a cellular systems biology profile the one or more tissue samples,
- wherein at least the steps of e) and f) are automated, thereby providing a method for cellular systems biology profiling of the one or more tissue samples.
A method for producing a cellular systems biology profile of one or more tissue samples, wherein the tissue sample is profiled for the presence of cancer, the stage of a cancer, the diagnosis of a cancer, the prognosis of a cancer, or combination thereof, comprising:
- a) obtaining at least two sections from one or more tissue samples, wherein the one or more tissue samples is selected from the group consisting a suspected cancerous tissue, a lymph node, and a combination thereof;
- b) labeling at least one section with a histological stain, thereby producing a histologically stained section;
- c) labeling at least one section with a panel of fluorescently labeled reagents, thereby producing a fluorescently labeled section, wherein each fluorescently labeled reagent is specific for a biomarker, and wherein the panel of fluorescently labeled reagents comprises fluorescently labeled reagents selected from the group consisting of:
- i) a set of fluorescently labeled reagents specific for at least four cancer cell biomarkers;
- ii) a set of fluorescently labeled reagents specific for at least four migratory immune cell biomarkers;
- iii) a combination of:
- A) a set of fluorescently labeled reagents specific for at least three cancer cell biomarkers;
- and
- B) a set of fluorescently labeled reagents specific for at least three migratory immune cell biomarkers;
- and
- iv) combinations thereof,
- wherein the panel of fluorescently labeled reagents detects at least four different biomarkers, and wherein the detection of a biomarker is a read-out of one or more features of a cellular systems biology profile;
- d) imaging the histologically stained section with at least a first optical mode, wherein the imaging produces a first set of data;
- e) imaging the fluorescently labeled section with at least a second optical mode, wherein the imaging produces a second set of data;
- f) analyzing the first set of data and second set of data to identify five or more features, wherein at least one feature is identified in each of the first set of data and the second set of data, and wherein the combination of the five or more features is a cellular systems biology profile of the one or more tissue samples,
- thereby providing a method for producing a cellular systems biology profile of the one or more tissue samples, wherein the tissue sample is profiled for the presence of a cancer, the stage of a cancer, the diagnosis of a cancer, the prognosis of a cancer or combination thereof.
A method for producing a cellular systems biology profile of one or more tissue samples, wherein the tissue sample is profiled for the presence, severity or absence of a tissue toxicity, comprising:
- a) obtaining at least two sections from one or more tissue samples;
- b) labeling at least one section with a histological stain, thereby producing a histologically stained section;
- c) labeling at least one section with a panel of fluorescently labeled reagents, thereby producing a fluorescently labeled section, wherein each fluorescently labeled reagent is specific for a biomarker, and wherein the panel of fluorescently labeled reagents comprises a set of fluorescently labeled reagents selected from the group consisting of:
- i) one or more fluorescently labeled reagents specific for cell metabolism biomarkers;
- ii) one or more fluorescently labeled reagents specific for DNA damage biomarkers;
- iii) one or more fluorescently labeled reagents specific for cell morphology biomarkers;
- iv) one or more fluorescently labeled reagents specific for DNA damage biomarkers;
- v) one or more fluorescently labeled reagents specific for cell differentiation biomarkers;
- vi) one or more fluorescently labeled reagents specific for stress-induced transcription activation or inhibition biomarkers;
- vii) one or more fluorescently labeled reagents specific for phosphorylation status of stress kinase biomarkers;
- viii) one or more fluorescently labeled reagents specific for apoptosis or necrosis biomarkers;
- ix) one or more fluorescently labeled reagents specific for cytoskeleton biomarkers;
- x) one or more fluorescently labeled reagents specific for organelle biomarkers;
- xi) one or more fluorescently labeled reagents specific for presence or activation of immune cell biomarkers;
- and
- xii) combinations thereof,
- wherein the panel of fluorescently labeled reagents detects at least four different biomarkers, and wherein the detection of a biomarker is a read-out of one or more features of a cellular systems biology profile;
- d) imaging the histologically stained section with at least a first optical mode, wherein the imaging produces a first set of data;
- e) imaging the fluorescently labeled section with at least a second optical mode, wherein the imaging produces a second set of data;
- f) analyzing the first set of data and second set of data to identify five or more features, wherein at least one feature is identified in each of the first set of data and the second set of data, and wherein the combination of the five or more features is a cellular systems biology profile of the one or more tissue samples,
- wherein at least the steps of d), e) and f) are automated, thereby providing a method for producing a cellular systems biology profile of the one or more tissue samples, wherein the tissue sample is profiled for the presence, severity or absence of a tissue toxicity.
Dependencies are inferred from the claim text.