US 12,012,633 B2
Lineage tracing using mitochondrial genome mutations and single cell genomics
Leif S. Ludwig, Cambridge, MA (US); Caleb A. Lareau, Boston, MA (US); Jacob C. Ulirsch, Boston, MA (US); Aviv Regev, Cambridge, MA (US); Vijay G. Sankaran, Boston, MA (US); Jason Buenrostro, Cambridge, MA (US); and Christoph Muus, Cambridge, MA (US)
Assigned to The Broad Institute, Inc., Cambridge, MA (US); Massachusetts Institute of Technology, Cambridge, MA (US); The Children's Medical Center Corporation, Boston, MA (US); and President and Fellows of Harvard College, Cambridge, MA (US)
Appl. No. 17/251,451
Filed by The Broad Institute, Inc., Cambridge, MA (US); Massachusetts Institute of Technology, Cambridge, MA (US); The Children's Medical Center Corporation, Boston, MA (US); and President and Fellows of Harvard College, Cambridge, MA (US)
PCT Filed Jun. 11, 2019, PCT No. PCT/US2019/036583
§ 371(c)(1), (2) Date Dec. 11, 2020,
PCT Pub. No. WO2019/241273, PCT Pub. Date Dec. 19, 2019.
Claims priority of provisional application 62/838,639, filed on Apr. 25, 2019.
Claims priority of provisional application 62/683,502, filed on Jun. 11, 2018.
Prior Publication US 2021/0246503 A1, Aug. 12, 2021
Int. Cl. C12Q 1/68 (2018.01); A61K 45/06 (2006.01); C12Q 1/6827 (2018.01); C12Q 1/6869 (2018.01); C12Q 1/6886 (2018.01)
CPC C12Q 1/6869 (2013.01) [A61K 45/06 (2013.01); C12Q 1/6827 (2013.01); C12Q 1/6886 (2013.01)] 27 Claims
 
1. A method of determining a lineage and/or clonal structure of single cells in a multicellular eukaryotic organism comprising:
a) detecting mutations in mitochondrial genome sequencing reads of single cells obtained from a subject; and
b) clustering the cells based on the presence of the mutations in the single cells, whereby a lineage and/or clonal structure for the single cells is retrospectively inferred.