	US 12,282,499 B1
	Database processing system for determining whether an entity affects a transition
Avak Kahvejian, Lexington, MA (US); Nicholas McCartney Plugis, Boston, MA (US); Michael Raymond Retchin, Columbus, OH (US); Fabian Alexander Wolf, Munich (DE); and Poorya Hosseini, Cambridge, MA (US)
Assigned to Flagship Pioneering Innovations VI, LLC, Cambridge, MA (US)
Filed by Flagship Pioneering Innovations VI, LLC, Cambridge, MA (US)
Filed on Oct. 11, 2023, as Appl. No. 18/485,119.
Application 18/485,119 is a continuation of application No. 16/511,691, filed on Jul. 15, 2019.
Claims priority of provisional application 62/805,888, filed on Feb. 14, 2019.
Claims priority of provisional application 62/805,884, filed on Feb. 14, 2019.
Claims priority of provisional application 62/698,701, filed on Jul. 16, 2018.
Int. Cl. G06F 16/28 (2019.01); G16B 50/00 (2019.01)

CPC G06F 16/288 (2019.01) [G16B 50/00 (2019.02)]

15 Claims

1. A method comprising:

A) performing, using a database processing system comprising one or more processors and a memory, a first database access call to access a single-cell transition signature representing a measure of differential cellular-component amount between a normal cell state and a diseased cell state, wherein the diseased cell state occurs through a transition, free of a perturbation, from the normal cell state to the diseased cell state, and wherein the first database access call identifies a plurality of cellular-components comprising at least 1000 cellular-components and, for each respective cellular-component in the plurality of cellular-components, a corresponding first association between (a) a change in amount of the respective cellular-component in a first plurality of first cellular-datasets and a second plurality of second cellular-component datasets and (b) a change in state between the normal state and the diseased cell state, wherein:

each respective first cellular-component dataset in the first plurality of first cellular-component datasets comprises amount data for the plurality of cellular-components for a corresponding single cell of a first sample of cells in the normal state,

the first plurality of first cellular-component datasets includes a respective first cellular-component dataset for each single cell of the first sample of cells and the first sample of cells comprises at least 10,000 cells,

each respective second cellular-component dataset in the second plurality of second cellular-component datasets comprises amount data for the plurality of cellular-components for a corresponding single cell of a second sample of cells in the diseased cell state, and

the second plurality of second cellular-component datasets includes a respective second cellular-component dataset for each single cell of the second sample of cells and the second sample of cells comprises at least 10,000 cells;

B) performing, using the database processing system, a second database access call to access a perturbation signature representing a measure of differential cellular-component amount between (i) a third sample of cells exposed to a vehicle and (ii) a fourth sample of cells, wherein the fourth sample of cells are exposed to the perturbation and the vehicle, wherein the perturbation signature comprises an identification of all or a portion of the plurality of cellular-components and, for each respective cellular-component in the all or the portion of the plurality of cellular-components, a corresponding second association between a change of amount of the respective cellular-component between a third plurality of cellular-component datasets and a fourth plurality of cellular-component datasets, wherein the third sample of cells, prior to exposure to the vehicle, are in the same state as the fourth sample of cells, prior to the exposure of the vehicle and the perturbation, wherein

each respective cellular-component dataset in the third plurality of third cellular-component datasets comprises amount data for the plurality of cellular-components for a corresponding single cell in the third sample of cells,

the third plurality of third cellular-component datasets includes a respective third cellular-component dataset for each single cell of the third sample of cells and the third sample of cells comprises at least 10,000 cells,

each respective cellular-component dataset in the fourth plurality of fourth cellular-component datasets comprises amount data for the plurality of cellular-components for a corresponding single cell in the fourth sample of cells, and

the fourth plurality of fourth cellular-component datasets includes a respective fourth cellular-component dataset for each single cell of the fourth sample of cells and the fourth sample of cells comprises at least 10,000 cells;

C) determining that the perturbation affects the transition, using the database processing system, and using (i) first associations in the single-cell transition signature and (ii) corresponding second associations in the perturbation signature; and

D) applying the perturbation to a subject that has a disease associated with the diseased state, thereby treating the subject.