Systems and methods for discriminating effects on targets

A method for determining whether a set of test perturbations discriminates over a null distribution for an on target effect against one or more first genetic components of a cell, wherein the set of test perturbations comprises a plurality of test perturbations against the one or more first genetic components and the cell comprises a plurality of genetic components including the first one or more genetic components, the method comprising:

• at a computer system comprising a processor and a memory:
• obtaining, for each respective test perturbation in the set of test perturbations, a corresponding test vector, thereby obtaining a plurality of test vectors, wherein each corresponding test vector comprises a plurality of test elements, each test element in the plurality of test elements comprising a test distribution metric of a respective dimension reduction component in a plurality of dimension reduction components computed using a measurement of a plurality of features across a plurality of instances of the cell upon exposure of the plurality of instances of the cell to the respective test perturbation, wherein the plurality of dimension reduction components of the test distribution metric is less than the plurality of features;
• computing a composite test metric, using the plurality of test vectors, the composite test metric quantifying the on target effect of the set of test perturbations against the first one or more genetic components, by a first process;
• computing the null distribution, wherein the null distribution comprises a plurality of composite control metrics, each respective composite control metric in the plurality of composite control metrics computed by a second process, which is different from the first process;
• and
• comparing the composite test metric to the null distribution, wherein, responsive to the composite test metric being differentiated from the null distribution based on the comparison, the set of test perturbations is deemed to discriminate the on target effect against the first one or more genetic components over the null distribution;
• and
• selecting for use in high throughput screening a target perturbation from the set of test perturbations which has been deemed to discriminate the on target effect, wherein the target perturbation is selected based on the comparison as being most representative of the on target effects with which to perturb one or more genes associated with a target;
• and
• performing the high throughput screening using the target perturbations, wherein cells used in the high throughput screening are exposed to the target perturbation and used as the basis of a screening assay for identification of compounds that, when exposed to the target perturbation exposed cells, reverse the on target effects exhibited by the target perturbation exposed cells.