Morphometric detection of DNA mismatch repair deficiency
AssigneeVisiongate, Inc.
InventorsDaniel J. Sussman, Michael G. Meyer, Randall Mastrangelo, Alan C. Nelson
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Abstract
A method to develop one or more morphometric classifiers to identify a mismatch repair deficiency (MMRD). The method provides a non-invasive method of characterizing MMRD that is responsive to a tumor in its early stages of development and irrespective of the tumor size. The method allows targeting cancer therapy to the specific characteristics of the cancer that the patient may have, allowing more efficient cancer management with far fewer side effects.
Claims4
A method for developing at least one more morphometric classifier to identify cells exhibiting Mismatch Repair Deficiency (MMRD), the method comprising:
- actuating a mirror to sweep a plane of focus through transduced cells, wherein projection images are integrated by the camera to create a pseudoprojection from each single perspective;
- deriving selected clones from the transduced cells, using a software-executed process that interfaces with opto-mechanical devices;
- using a 3D optical tomography system for MLH1 expression to identify a subset of MLH1 expression clones by viewing the projection images of the selected clones from multiple angular positions;
- using immunohistochemistry antibodies to select the subset of MLH1 expression clones to identify those with MLH1 expression levels reduced in comparison to a parental cell line to identify a second subset of the selected clones;
- expanding the second subset of the selected clones in culture;
- harvesting the second subset of the selected clones;
- using the selected clones and 3D cell classifications to generate a morphometric classifier, via the 3D optical tomography system, for non-invasively characterizing MMRD;
- using a classification cascade to train the morphometric classifier to identify specific mutations associated with different cancer types, wherein the training produces a series of binary classifiers to isolate malignant cells from normal cells;
- using the morphometric classifier trained on the selected clones to detect cancer drivers in the MMRD;
- and
- treating a patient with an immune checkpoint inhibitor agent, in response to detecting cancer drivers in the MMRD, wherein the morphometric classifier detects cancer with equal sensitivity irrespective of tumor histology, stage, and size.
Dependencies are inferred from the claim text.