A non-transitory computer-readable medium storing one or more computer programs, executable by a computer, for associating a test chemical compounds with a physiological condition of interest, the computer comprising one or more processors and a memory, the one or more computer programs collectively encoding computer executable instructions that perform a method comprising:
- (A) accessing, in electronic form, a set of cellular constituent modules, a latent representation, and a count data structure, wherein
- each respective cellular constituent module in the set of cellular constituent modules includes a respective independent subset of a plurality of cellular constituents,
- a corresponding plurality of cell-based assay abundance values for each respective independent subset of the plurality of cellular constituents separately correlate across a plurality of different states associated with the physiological condition,
- a first cellular constituent module in the set of cellular constituent modules is associated with the physiological condition of interest and includes a first subset of cellular constituents that represent the physiological condition,
- the latent representation comprises a plurality of weights, each respective weight way in the plurality of weights corresponding to both (i) a corresponding cellular constituent module x in the set of cellular constituent modules and (ii) a corresponding cellular constituent y in the plurality of cellular constituents, wherein each respective weight wx-y in the plurality of weights is formed from single cell expression data for the set of cellular constituents from a first plurality of at least 500 cells that collectively represent the plurality of different states associated with the physiological condition, and
- the count data structure is formed from single cell abundance data for the plurality of cellular constituents from a second plurality of at least 500 cells, wherein each cell in the second plurality of cells is exposed to a training compound n in the plurality of training compounds, and wherein the count data structure comprises a count cntc-y for each combination of (i) a cell c in the second plurality of at least 500 cells and (ii) a cellular constituent y in the plurality of cellular constituents;
- (B) determining, for each respective training compound n in the plurality of training compounds, for each respective cellular constituent module x in the set of cellular constituent modules, a corresponding activation score actn-x wherein,
- actn-x=Σy=1Qwx-y*cntc-y
- wherein,
- c is a cell in the plurality of cells that has been exposed to the respective training compound n, and
- Q is a total number of cellular constituents in the plurality of cellular constituents;
- (C) obtaining a model comprising 1000 or more parameters, wherein for each respective training compound in the plurality of training compounds, upon input of a fingerprint of a chemical structure of the respective training compound n into the model, the 1000 or more parameters are applied against the fingerprint of the chemical structure to produce a predicted activation score that has concordance with the corresponding activation score actn-x of the respective training compound for the first cellular constituent module;
- (D) obtaining, in electronic form, a fingerprint of a chemical structure of the test chemical compound;
- (E) responsive to inputting the fingerprint of the chemical structure of the test chemical compound into the model, retrieving, as output from the model, a calculated activation score for the test chemical compound for the first cellular constituent module;
- and
- (F) associating the test chemical compound with the physiological condition of interest when the calculated activation score for the test chemical compound for the first cellular constituent module satisfies a first threshold criterion.