IP Library › Granted Patent US 12,300,357
Granted Patent B2
US 12,300,357 · App. 15/838,724 · Granted May 13, 2025

Applied computer technology for management, synthesis, visualization, and exploration of parameters in large multi-parameter data sets

Inventors: James Edward Almarode (Lebanon, OR); Josef Spidlen (Coquitlam, CA); Michael David Stadnisky (Ashland, OR)
Assignee: FlowJo, LLC
G16B45/00C12N15/10C12N15/1089G01N15/10G01N33/48G16B25/00G16B50/00G16B50/10G16B50/30G01N2015/1006G01N2015/1402
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Quick Facts
Patent No.
US 12,300,357
App. No.
15/838,724
Granted
May 13, 2025
Kind
B2
Abstract

Computer technology is disclosed that applies innovative data processing and visualization techniques to large multi-parameter data sets such as cellular gene expression data to find new relationships such as relationships between cells and genes and create new associative data structures within the data sets that represent these relationships. For example, scatterplots of gene expression data can be iteratively pivoted between a cell view and a gene view to find cell populations and gene sets of interest to a user.

Claims (81)

1. A computing-implemented method of visualizing a multi-parameter data set performed by one or more processors executing program instructions, the method comprising:

receiving a multi-parameter data set comprising cellular gene expression data generated by flow cytometry equipment based on a plurality of cells, the multi-parameter data set including a plurality of data items, each data item associated with a plurality of parameters corresponding to expression of a plurality of genes and including data values for each of the associated parameters;

providing a user interface to a user for visualizing the multi-parameter data set across a first axis and a second axis, wherein the user interface is configured to enable the user to select a first parameter from among the plurality of parameters to associate with the first axis and a second parameter from among the plurality of parameters to associate with the second axis;

receiving a first user input from the user via the user interface, wherein the first user input comprises a selection of a first parameter associated with the first axis and a second parameter associated with the second axis;

generating, within the user interface, a cell view scatterplot of the multi-parameter data set across the first and second axes, wherein the first and second axes correspond to the user-selected first and second parameters within the multi-parameter data set, the cell view scatterplot comprising a first plurality of dots, each dot in the first plurality of dots corresponding to a data item from the multi-parameter data set and being positioned on the cell view scatterplot at a position along the first and second axes at a location corresponding to the data values for the parameters corresponding to the axes;

receiving a second user input from the user via the user interface, wherein the second user input comprises a selection of a first cell population associated with the first axis and a second cell population associated with the second axis;

in response to receiving the second user input, pivoting from the cell view scatterplot to a gene view scatterplot by generating, within the user interface, the gene view scatterplot comprising a second plurality of dots, wherein the second plurality of dots correspond to a plurality of different genes expressed by the first and the second cell populations, and each dot of the second plurality of dots is positioned on the first and second axis of the gene view scatterplot based on expression of the corresponding gene by the first and second cell populations;

receiving, from the user via the user interface, a gate creation input defining a gated gene set comprising a subset of the plurality of different genes;

creating a synthetic parameter data object in a workspace, the synthetic parameter data object comprising, for individual cells of the plurality of cells, synthetic parameter values calculated based on two or more genes from the gated gene set;

augmenting the cellular gene expression data such that the synthetic parameter values are associated with cells in the cellular gene expression data; and

displaying, within the user interface, a second cell view scatterplot presenting a focused view of a cluster of cells, at least the first axis or the second axis in the second cell view scatterplot corresponding to the synthetic parameter.

2. The method of claim 1 , wherein the data values for each of the parameters comprise data indicative of counts for expressions of the corresponding genes in the cell corresponding to that particular data item.

3. The method of claim 2 , wherein the gene view scatterplot is generated from the cellular gene expression data based on user specification of a plurality of cell populations.

4. The method of claim 3 , wherein the pivoting from the cell view scatterplot to the gene view scatterplot is performed in response to the user specification of the plurality of cell populations.

5. The method of claim 3 , further comprising:

generating a gene set by gating a plurality of genes in the gene view scatterplot.

6. The method of claim 5 , further comprising:

pivoting to the cell view scatterplot from the gene view scatterplot based on a user specification of a gene set for use as an axis parameter in the cell view scatterplot.

7. The method of claim 2 , wherein the cellular gene expression data comprises a plurality of stochastic labels derived from stochastic labeling of a sample.

8. The method of claim 1 , further comprising:

receiving, via the user interface, a user specification of a new first parameter associated with the first axis; and

updating, within the user interface, the cell view scatterplot based on the user specification of the new first parameter associated with the first axis of the cell view scatterplot.

9. The method of claim 1 , further comprising repeating the creating, translating, and presenting steps to create a plurality of data objects in the workspace that represent a plurality of cell populations.

10. The method of claim 1 , further comprising:

gating a group of dots in the second cell view scatterplot based on the defined gene set to define another cell population; and

creating a data object in the workspace that is representative of the defined another cell population.

11. An apparatus comprising:

a memory configured to store a multi-parameter data set;

a processor for cooperation with the memory, the processor configured to perform the method of claim 1 , and

a display in cooperation with the processor, wherein the display is configured to graphically present the cell view scatterplot and the gene view scatterplot.

12. The apparatus of claim 11 , wherein the multi-parameter data set comprises cellular gene expression data, the data items comprising a plurality of cells, wherein the parameters comprise a plurality of genes, and wherein the data values for each of the parameters associated with a particular data item comprise data indicative of counts for expressions of the corresponding genes in the cell corresponding to that particular data item.

13. The method of claim 1 , wherein the cell view scatterplot or the second cell view scatterplot comprises at least a first subset of dots corresponding to cells having a zero value for at least the parameter corresponding to the first axis and a second subset of dots corresponding to cells having a zero value for at least the parameter corresponding to the second axis.

14. The method of claim 13 , further comprising displaying the cell view scatterplot or the second cell view scatterplot in a spread zeros format comprising:

a first two-dimensional quadrant containing dots having a zero value for the parameters corresponding to both the first axis and the second axis;

a second two-dimensional quadrant containing dots having a zero value for the parameter corresponding to the first axis and positive values for the parameter corresponding to the second axis;

a third two-dimensional quadrant containing dots having positive values for the parameter corresponding to the first axis and a zero value for the parameter corresponding to the second axis; and

a fourth two-dimensional quadrant containing dots having positive values for the parameters corresponding to both the first axis and the second axis.

15. The method of claim 1 , wherein the synthetic parameter values are calculated based on a summation of the two or more genes from the gated gene set.

16. A computer program product comprising:

a plurality of processor-executable instructions that are resident on a non-transitory computer readable storage medium, wherein the instructions are configured, upon execution by a processor, to cause the processor to:

receive a multi-parameter data set comprising cellular gene expression data generated by flow cytometry equipment based on a plurality of cells, the multi-parameter data set including a plurality of data items, each data item associated with a plurality of parameters corresponding to expression of a plurality of genes and including data values for each of the associated parameters;

provide a user interface to a user for visualizing the multi-parameter data set across a first axis and a second axis, wherein the user interface is configured to enable the user to select a first parameter from among the plurality of parameters to associate with the first axis and a second parameter from among the plurality of parameters to associate with the second axis;

receive a first user input from the user via the user interface, wherein the first user input comprises a selection of a first parameter associated with the first axis and a second parameter associated with the second axis;

generate, within the user interface, a cell view scatterplot of a multi-parameter data set across the first and second axes, wherein the first and second axes correspond to user-selected first and second parameters within the multi-parameter data set, the cell view scatterplot comprising a first plurality of dots, each dot in the first plurality of dots corresponding to a data item from the multi-parameter data set and being positioned on the cell view scatterplot at a position along the first and second axes at a location corresponding to the data values for the parameters corresponding to the axes;

receive a second user input from the user via the interface, wherein the second user input comprises a selection of a first cell population associated with the first axis and a second cell population associated with the second axis;

in response to receiving the second user input, pivot from the cell view scatterplot to a gene view scatterplot by generating, within the user interface, the gene view scatterplot comprising a second plurality of dots, wherein the second plurality of dots correspond to a plurality of different genes expressed by the first and the second cell populations, and each dot of the second plurality of dots is positioned on the first and second axis of the gene view scatterplot based on expression of the corresponding gene by the first and second cell populations;

receiving, from the user via the user interface, a gate creation input defining a gated gene set comprising a subset of the plurality of different genes;

create a synthetic parameter data object in a workspace, the synthetic parameter data object comprising, for individual cells of the plurality of cells, synthetic parameter values calculated based on two or more genes from the gated gene set;

augment the cellular gene expression data such that the synthetic parameter values are associated with cells in the cellular gene expression data; and

display, within the user interface, a second cell view scatterplot presenting a focused view of a cluster of cells, at least the first axis or the second axis in the second cell view scatterplot corresponding to the synthetic parameter.

17. The computer program product of claim 16 , wherein the instructions are further configured to cause the processor to:

generate a gene view scatterplot of cellular gene expression data based on user specification of a plurality of cell populations.

18. The computer program product of claim 16 , wherein the instructions are further configured to cause the processor to:

pivot to a cell view scatterplot from the gene view scatterplot based on a user specification of a gene set for use as an axis parameter in the cell view scatterplot.

19. The computer program product of claim 16 , wherein the cell view scatterplot or the second cell view scatterplot comprises at least a first subset of dots corresponding to cells having a zero value for at least the parameter corresponding to the first axis and a second subset of dots corresponding to cells having a zero value for at least the parameter corresponding to the second axis.

20. The computer program product of claim 19 , wherein the instructions are further configured to cause the processor to display the cell view scatterplot or the second cell view scatterplot in a spread zeros format comprising:

a first two-dimensional quadrant containing dots having a zero value for the parameters corresponding to both the first axis and the second axis;

a second two-dimensional quadrant containing dots having a zero value for the parameter corresponding to the first axis and positive values for the parameter corresponding to the second axis;

a third two-dimensional quadrant containing dots having positive values for the parameter corresponding to the first axis and a zero value for the parameter corresponding to the second axis; and

a fourth two-dimensional quadrant containing dots having positive values for the parameters corresponding to both the first axis and the second axis.

21. The computer program product of claim 16 , wherein the synthetic parameter values are calculated based on a summation of the two or more genes from the gated gene set.

22. A system comprising:

one or more processors; and

a non-transitory computer readable storage medium having stored thereon computer-executable instructions that, upon execution by the one or more processors, cause the one or more processors to:

receive a multi-parameter data set comprising cellular gene expression data generated by flow cytometry equipment based on a plurality of cells, the multi-parameter data set including a plurality of data items, each data item associated with a plurality of parameters corresponding to expression of a plurality of genes;

provide a user interface to a user for visualizing the multi-parameter data set across a first axis and a second axis, wherein the user interface is configured to enable the user to select a first parameter from among the plurality of parameters to associate with a first axis and a second parameter from among the plurality of parameters to associate with a second axis;

receive a first user input from the user via the user interface, wherein the first user input comprises a selection of a first parameter associated with the first axis and a second parameter associated with the second axis;

generate, within the user interface, a cell view scatterplot of a multi-parameter data set across the first and second axes, wherein the first and second axes correspond to user-selected first and second parameters within the multi-parameter data set, the cell view scatterplot comprising a first plurality of dots, each dot in the first plurality of dots corresponding to a data item from the multi-parameter data set and being positioned on the cell view scatterplot at a position along the first and second axes at a location corresponding to the data values for the parameters corresponding to the axes;

receive a second user input from the user via the interface, wherein the second user input comprises a selection of a first cell population associated with the first axis and a second cell population associated with the second axis;

in response to receiving the second user input, pivot from the cell view scatterplot to a gene view scatterplot by generating, within the user interface, the gene view scatterplot comprising a second plurality of dots, wherein the second plurality of dots correspond to a plurality of different genes expressed by the first and the second cell populations, and each dot of the second plurality of dots is positioned on the first and second axis of the gene view scatterplot based on expression of the corresponding gene by the first and second cell populations;

receive, from the user via the user interface, a gate creation input defining a gated gene set comprising a subset of the plurality of different genes;

create a synthetic parameter data object in a workspace, the synthetic parameter data object comprising, for individual cells of the plurality of cells, synthetic parameter values calculated based on two or more genes from the gated gene set;

augment the cellular gene expression data such that the synthetic parameter values are associated with cells in the cellular gene expression data; and

display, within the user interface, a second cell view scatterplot presenting a focused view of a cluster of cells, at least the first axis or the second axis in the second cell view scatterplot corresponding to the synthetic parameter.

23. The system of claim 22 , wherein the cell view scatterplot or the second cell view scatterplot comprises at least a first subset of dots corresponding to cells having a zero value for at least the parameter corresponding to the first axis and a second subset of dots corresponding to cells having a zero value for at least the parameter corresponding to the second axis.

24. The system of claim 23 , wherein the instructions are further configured to cause the one or more processors to display the cell view scatterplot or the second cell view scatterplot in a spread zeros format comprising:

a first two-dimensional quadrant containing dots having a zero value for the parameters corresponding to both the first axis and the second axis;

a second two-dimensional quadrant containing dots having a zero value for the parameter corresponding to the first axis and positive values for the parameter corresponding to the second axis;

a third two-dimensional quadrant containing dots having positive values for the parameter corresponding to the first axis and a zero value for the parameter corresponding to the second axis; and

a fourth two-dimensional quadrant containing dots having positive values for the parameters corresponding to both the first axis and the second axis.

25. The system of claim 22 , wherein the synthetic parameter values are calculated based on a summation of the two or more genes from the gated gene set.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2018
From: ALMARODE, JAMES EDWARD; SPIDLEN, JOSEF; STADNISKY, MICHAEL DAVID
To: FLOWJO, LLC
Reel/Frame 047085/0673 →
Continuity (2)
Provisional Application 62433930 · Dec 14, 2016
Related Publication 20180165414A1 · Jun 14, 2018
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