Systems and methods for automated characterization of genetic heterogeneity in tissue samples

A method for automated determination of tissue characteristics, the method comprising:

• obtaining an image of a tissue sample, the image depicting cell nuclei and corresponding biomarkers in the tissue sample;
• and,
• by a computer executing software instructions:
• processing the image to identify in the image:
• the cell nuclei, corresponding biomarkers associated with the cell nuclei, and spatially-connected groups of the cell nuclei;
• computing characters of the spatially-connected groups of cell nuclei;
• and,
• based at least in part on the computed characters, highlighting regions corresponding to the spatially-connected groups of cell nuclei;
• wherein identifying the spatially-connected groups of the cell nuclei in the image comprises:
• identifying a selected set of the cell nuclei for which the corresponding biomarkers satisfy a selection criterion;
• establishing a network of cell-to-cell connections connecting adjacent ones of the cell nuclei;
• identifying first and second disjoint groups of the cell nuclei of the selected set, each of the first and second groups comprising a plurality of the cell nuclei of the selected set that are interconnected by at least one chain of the cell-to-cell connections;
• and,
• determining whether a gap comprising one or more cell nuclei that are not members of either the first or second groups satisfies a rule and, if so, uniting the first and second groups.

A method for automated determination of tissue characteristics, the method comprising:

• obtaining an image of a tissue sample, the image depicting cell nuclei and corresponding biomarkers in the tissue sample;
• and,
• by a computer executing software instructions:
• processing the image to identify the cell nuclei and corresponding biomarkers in the image and to identify spatially-connected groups of the cell nuclei in the image;
• and
• computing characters of the spatially-connected groups of cell nuclei;
• wherein identifying spatially-connected groups of the cell nuclei in the image comprises:
• identifying a selected set of the cell nuclei for which the corresponding biomarkers satisfy a selection criterion;
• establishing a network of cell-to-cell connections connecting adjacent ones of the cell nuclei;
• and
• identifying a group of the cell nuclei of the selected set that are all interconnected by at least one chain of the cell-to-cell connections wherein:
• the at least one chain passes only through cells of the selected set except for in at least one gap in which the chain passes through from 1 to n consecutive cells that are not in the selected set and at least one pair of cells in the group is not interconnected by any chain of the cell-to-cell connections that passes only through cells of the selected set.

A method for automated determination of tissue characteristics, the method comprising:

• obtaining an image of a tissue sample, the image depicting cell nuclei and corresponding biomarkers in the tissue sample;
• processing the image to identify the cell nuclei and corresponding biomarkers in the image and establishing a network of cell-to-cell connections connecting adjacent ones of the cell nuclei;
• identifying a selected set of the cell nuclei for which the corresponding biomarkers satisfy a selection criterion;
• and,
• identifying at least one spatially-connected group of the cell nuclei in the selected set by:
• finding first and second subsets of the spatially-connected group of the cell nuclei such that all of the cells within each of the first and second subsets are connected by some chain of the cell-to-cell connections that does not connect to any cell not in the subset;
• determining that a gap separating a first cell in the first subset from a second cell in the second subset has a size not exceeding a threshold;
• combining the first and second subsets into a group;
• and
• identifying a group of the cell nuclei of the selected set that are all interconnected by at least one chain of the cell-to-cell connections wherein:
• the at least one chain passes only through cells of the selected set except for in at least one gap in which the chain passes through from 1 to n consecutive cells that are not in the selected set and at least one pair of cells in the group is not interconnected by any chain of the cell-to-cell connections that passes only through cells of the selected set;
• and,
• computing a character for the group of cells.