Methods and Systems for Generating Cell Lineage Tree of Multiple Cell Samples

• US 20090292482A1
• Filed: 03/27/2006
• Published: 11/26/2009
• Est. Priority Date: 03/30/2005
• Status: Active Grant

• Current Assignee: Yeda Research and Development Co. Ltd. (Weizmann Institute of Science)
• Original Assignee: Yeda Research and Development Co. Ltd. (Weizmann Institute of Science)
• Inventors: Wasserstrom, Adam, Frumkin, Dan, Feige, Uriel, Kaplan, Shai, Shapiro, Ehud Y.
• Granted Patent: US 7,917,306 B2
• Time in Patent Office: Days
• US Class Current: 702/20
• CPC Class Codes: G16B 10/00 ICT specially adapted for evolutionary bioinformatics, e.g. phylogenetic tree construction or analysis
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: G16B 20/50 Mutagenesis
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 40/10 Signal processing, e.g. from mass spectrometry [MS] or from PCR

Abstract

A method of generating a cell lineage tree of a plurality of cells of an individual is provided. The method comprising: (a) determining at least one genotypic marker for each cell of the plurality of cells; and (b) computationally clustering data representing the at least one genotypic marker to thereby generate the cell lineage tree of the plurality of cells of the individual.

Claims

1. A method of generating a cell lineage tree of a plurality of cells of an individual, the method comprising:

(a) determining at least one genotypic marker for each cell of the plurality of cells; and

(b) computationally clustering data representing said at least one genotypic marker to thereby generate the cell lineage tree of the plurality of cells of the individual.

2. The method of claim 1, wherein the method further comprises extracting from said cell lineage tree cell-depth distribution within the cell lineage tree.

3. The method of claim 1, wherein said genotypic marker is a cell division marker.

4. The method of claim 1, wherein said genotypic marker exhibits somatic variability.

5. The method of claim 4, wherein said genotypic marker exhibiting somatic variability is a repetitive sequence element.

7. The method of claim 1, wherein said clustering is effected by a clustering algorithm.

9. The method of claim 1, wherein the plurality of cells comprises clones each of a single cell.

10. The method of claim 1, wherein the plurality of cells are derived from at least one tissue of the individual.

6. (canceled)

8. (canceled)

11. (canceled)

12. A method of assessing clonality of a neoplasm in an individual, the method comprising:

(a) obtaining a cell sample of the neoplasm of the individual;

(b) determining at least one genotypic market for each cell of said cell sample of the neoplasm; and

(c) computationally clustering data representing said at least one genotypic marker and additional genotypic markers of a plurality of cells, to thereby assess clonality of the neoplasm in the individual.

13. The method of claim 12, wherein said genotypic marker is a cell division marker.

14. The method of claim 12, wherein said genotypic marker exhibits somatic variability.

15. The method of claim 14, wherein said genotypic marker exhibiting somatic variability is a repetitive sequence element.

17. The method of claim 12, wherein said clustering is effected by a clustering algorithm.

19. The method of claim 12, wherein the neoplasm is of a blood forming tissue.

21. The method of claim 12, wherein the neoplasm is a cancer of unknown primary tumor.

16. (canceled)

18. (canceled)

20. (canceled)

22. A method of identifying presence of tumor stem cells, the method comprising:

(a) determining at least one genotypic marker for each cell of a cell sample of a tumor;

(b) computationally clustering data representing said at least one genotypic marker to thereby generate a cell lineage tree of said tumor; and

(c) mapping cells in said cell lineage tree, thereby identifying the presence of tumor stem cells.

23. The method of claim 22, wherein said genotypic marker is a cell division marker.

24. The method of claim 22, wherein said genotypic marker exhibits somatic variability.

25. The method of claim 24, wherein said genotypic marker exhibiting somatic variability is a repetitive sequence element.

27. The method of claim 22, wherein said clustering is effected by a clustering algorithm.

26. (canceled)

28. (canceled)

29. A system for generating a cell-lineage tree of a plurality of cells, the system comprising a processing unit, said processing unit executing a software application configured for:

(i) determining at least one genotypic marker for each cell of the plurality of cells; and

(ii) clustering data representing said at least one genotypic marker and producing a cell-lineage tree of the plurality of cells.

30-39. -39. (canceled)

40. A method of assessing growth dynamics of a population of cells of interest, the method comprising determining cell depth of at least two samples of the population of cells of interest, each of said two samples being of a different age, thereby assessing growth dynamics of the population of cells of interest.

41. The method of claim 40, wherein the population of cells comprises a population of neuronal cells.

42. The method of claim 40, wherein the population of cells comprises a population of stem cells.

43-44. -44. (canceled)