Biological data annotation and visualization

Patent metadata

Field	Value
Publication number	US-2016357906-A1
Application number	US-201514730037-A
Country	US
Kind code	A1
Filing date	Jun 3, 2015
Priority date	Jun 3, 2015
Publication date	Dec 8, 2016
Grant date	—

Abstract

Identification of regions-of-interest within cell maps is disclosed. In certain embodiments, identification of the regions-of interest is based on the use of a plurality of biomarkers, which may be used to generate a multiplexed image of a tissue sample. Based on the identified regions, cells may be extracted and localized sequence data may be generated specific to the regions-of-interest.

First claim

1 . A method for acquiring region-of-interest specific sequence data, comprising:
selecting a plurality of probes of interest; generating a cell map comprising an image of a tissue sample on which biomarker expression data generated using the selected probes is displayed; identifying one or more regions-of-interest within the cell map in which cells are tagged by one or more of the probes; extracting one or more cells from at least one of the regions-of-interest from the tissue sample; and sequencing the one or more cells to generate region-of-interest based sequence data.

2 . The method of claim 1 , wherein the nucleic acid sequence data comprises mutation information associated with the one or more cells within the regions-of-interest.

3 . The method of claim 1 , wherein the plurality of probes comprise labeled or tagged antibodies.

4 . The method of claim 1 , wherein the cell map comprises a multiplexed image of the tissue sample.

5 . The method of claim 1 , further comprising:
selecting additional probes based on the region-of-interest based sequence data; generating an updated cell map comprising an updated image of the tissue sample exposed to the additional probes; identifying one or more additional regions-of-interest within the updated cell map in which cells are tagged by one or more of the probes; and extracting one or more additional cells from at least one of the additional regions-of-interest from the tissue sample; and sequencing the one or more additional cells to generate additional region-of-interest based sequence data.

6 . The method of claim 1 , wherein identifying one or more regions-of-interest within the cell map comprises identifying regions-of-interest exhibiting expression of proteins, nucleic acids, or other biological activity of interest.

7 . The method of claim 1 , wherein extracting one or more cells from at least one of the regions-of-interest from the tissue sample comprises extracting a sequencing region from the tissue sample at a spatial location corresponding to a respective region-of-interest.

8 . The method of claim 7 , wherein the respective region-of-interest corresponds to a field-of-view of the cell map and the sequencing region differ in one or both of size or shape from the field-of-view.

9 . A method for acquiring spatially selected nucleic acid sequence data, comprising:
generating a multiplexed immunofluorescent (IF) image of a tissue sample using a plurality of IF probes; identifying one or more regions-of-interest within the multiplexed IF image, wherein the regions-of-interest exhibit biomarker expression to at least one of the plurality of IF probes; sampling one or more of the regions-of-interest to acquire cells from the sampled regions-of-interest; sequencing the acquired cells to generate a mutational profile for the acquired cells.

10 . The method of claim 9 , wherein the plurality of IF probes is selected from a larger library of IF probes.

11 . The method of claim 9 , wherein the plurality of IF probes comprise labeled or tagged antibodies.

12 . The method of claim 9 , wherein the biomarker expression is indicative of expression of proteins, nucleic acids, or other biological activity of interest.

13 . The method of claim 9 , comprising:
based upon the mutational profile, selecting additional IF probes; generating a second multiplexed IF image of the tissue sample using the additional IF probe; identifying one or more additional regions-of-interest within the second multiplexed IF image, wherein the additional regions-of-interest exhibit biomarker expression to at least one of the additional IF probes.

14 . The method of claim 9 , wherein the mutation profile comprises nucleic acid sequence data for the acquired cells.

15 . A processor-based system, comprising:
one or both of a memory or storage device storing one or more executable routines for the analysis of region-specific nucleic acid sequence data and cellular or sub-cellular biomarker data; one or more processors configured to execute the one or more executable routines which, when executed cause acts to be performed comprising:
generating a multiplexed immunofluorescent (IF) image of a tissue sample exposed to a plurality of probes;
displaying one or more regions-of-interest within the multiplexed IF image, wherein the regions-of-interest exhibit biomarker expression to at least one of the plurality of probes; and
upon sequencing of cells extracted from the regions-of-interest, displaying sequence data for the extracted cells.

16 . The processor-based system of claim 15 , wherein the sequence data comprises a mutational profile of the extracted cells.

17 . The processor-based system of claim 15 , wherein the one or more executable routines, when executed, identify one or more fields-of-view corresponding to the regions-of-interest and wherein displaying the one or more regions-of-interest comprises displaying the fields-of-view.

18 . The processor-based system of claim 15 , wherein the biomarker expression is indicative of expression of proteins, nucleic acids, or other biological activity of interest.

19 . The processor-based system of claim 15 , wherein the plurality of probes comprise labeled or tagged antibodies.

20 . The processor-based system of claim 15 , wherein the routines, when executed, perform iterated steps which generate subsequent multiplexed IF images using probes selected based on the sequence data determined for the regions of interest.

Assignees

• Gen Electric

Inventors

• Sarachan Brion Daryl
• Graf John Frederick

Classifications

• G01N21/6456

  Spatial resolved fluorescence measurements; Imaging · CPC title

• G16B45/00 Primary

  ICT specially adapted for bioinformatics-related data visualisation, e.g. displaying of maps or networks · CPC title

• G16B25/00

  ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression · CPC title

• C12Q1/6841

  In situ hybridisation · CPC title

• G01N2201/12

  Circuits of general importance; Signal processing · CPC title