Active learning for discovering pairwise interactions via representation learning
The present disclosure relates to systems, non-transitory computer-readable media, and methods that a implement a framework for active learning to discover pairwise interactions via representation learning. Indeed, in one or more implementations, the disclosed systems generate a first individual perturbation embedding from a first representation of a first cell exposed to a first perturbation and a second individual perturbation embedding, from a second representation of a second cell exposed to a second perturbation. For instance, the disclosed systems combine the first individual perturbation embedding and the second individual perturbation embedding to determine a predicted pairwise embedding. Moreover, in some instances, the disclosed systems generate a pairwise embedding from a representation of a cell exposed to both the first and second perturbation. Additionally, from comparing the predicted pairwise embedding with the pairwise embedding, the disclosed systems generate a measure of biological interaction of the first and second perturbation.
1 . A method comprising:
receiving a first digital image of a first biological cell exposed to a first perturbation, wherein the first perturbation comprises a first gene knockout of a first gene of the first biological cell or a first compound treatment of the first biological cell;
generating, utilizing a neural network machine learning model, a first individual perturbation feature vector, from the first digital image of the first biological cell exposed to the first perturbation;
receiving a second digital image of a second biological cell exposed to a second perturbation, wherein the second perturbation comprises a second gene knockout of a second gene of the second biological cell or a second compound treatment of the second biological cell;
generating, utilizing the neural network machine learning model, a second individual perturbation feature vector, from the second digital image of the second biological cell exposed to the second perturbation;
generating a predicted pairwise feature vector for the first biological cell individually exposed to the first perturbation and the second biological cell individually exposed to the second perturbation by combining the first individual perturbation feature vector and the second individual perturbation feature vector;
receiving a third digital image of a third biological cell exposed to a perturbation pair comprising both the first perturbation and the second perturbation;
generating, utilizing the neural network machine learning model, a double perturbation pairwise feature vector from the third digital image of the third biological cell exposed to the perturbation pair comprising both the first perturbation and the second perturbation;
generating a measure of biological interaction between the first perturbation and the second perturbation by comparing the predicted pairwise feature vector from the first digital image and the second digital image with the double perturbation pairwise feature vector from the third digital image, wherein the measure of biological interaction indicates a difference between biological cell response from exposure to the first perturbation and the second perturbation individually relative to biological cell response from exposure to the first perturbation and the second perturbation in combination;
generating an incomplete biological interaction matrix arranged according to a plurality of perturbation pairs, wherein the incomplete biological interaction matrix comprises the measure of biological interaction for the perturbation pair as an entry in the incomplete biological interaction matrix and further comprises additional measures of biological interactions as additional entries in the incomplete biological interaction matrix that correspond to additional perturbation pairs of the plurality of perturbation pairs;
generating, utilizing an active learning model that takes as inputs entries comprising the measure of biological interaction and the additional measures of biological interaction in the incomplete biological interaction matrix, predicted pairwise perturbation interaction scores corresponding to incomplete entries in the incomplete biological interaction matrix;
based on the predicted pairwise perturbation interaction scores, selecting additional perturbations for experimentation from the incomplete biological interaction matrix, wherein the additional perturbations for experimentation correspond to incomplete entries in the incomplete biological interaction matrix; and
performing a downstream experiment for a fourth biological cell by perturbing the fourth biological cell according to the additional perturbations selected from the incomplete biological interaction matrix.
2 . The method of claim 1 , wherein:
receiving the first digital image comprises receiving a first captured image of the first biological cell with a first modified cell phenotype resulting from the first gene knockout of the first gene; and
receiving the second digital image comprises receiving a second captured image of the second biological cell with a second modified cell phenotype resulting from the second gene knockout of the second gene.
3 . The method of claim 1 , wherein determining the predicted pairwise feature vector for the first perturbation and the second perturbation comprises:
determining a first normalized feature vector from the first individual perturbation feature vector and a control feature vector and a second normalized feature vector from the second individual perturbation feature vector and the control feature vector; and
combining the first normalized feature vector and the second normalized feature vector to determine the predicted pairwise feature vector for the first perturbation and the second perturbation.
4 . The method of claim 1 , further comprising generating the double perturbation pairwise feature vector from the third digital image portraying the third biological cell exposed to a double gene knockout of the first gene and the second gene in the third biological cell.
5 . The method of claim 1 , wherein generating the incomplete biological interaction matrix comprises generating a matrix that includes pairwise perturbation experiment data corresponding to actual pairwise perturbations and predictions of measures of biological interactions corresponding to perturbation pairs.
6 . The method of claim 5 , further comprises generating, utilizing the active learning model that comprises a pairwise prediction model, the predicted pairwise perturbation interaction scores for individual perturbations and corresponding information gain predictions based on the incomplete biological interaction matrix, wherein the corresponding information gain predictions indicate an amount of potential increase in knowledge relative to the incomplete biological interaction matrix in response to a selection of the additional perturbations for experimentation.
7 . The method of claim 6 , wherein utilizing the active learning model comprises an active-matrix completion algorithm to select a first entry from a plurality of entries of the incomplete biological interaction matrix based on the predicted pairwise perturbation interaction scores for the individual perturbations and the corresponding information gain predictions.
8 . The method of claim 1 , further comprising:
based on performing the downstream experiment for the fourth biological cell, determining additional measure of biological interaction for the additional perturbations selected from the incomplete biological interaction matrix; and
updating the incomplete biological interaction matrix to include the additional measure of biological interaction for the additional perturbations.
9 . A method comprising:
receiving a first digital image of a first biological cell exposed to a first gene knockout of a first gene of the first biological cell;
generating, utilizing a neural network machine learning model, a first individual perturbation feature vector, from the first digital image of the first biological cell exposed to the first gene knockout;
receiving a second digital image of a second biological cell exposed to a second gene knockout of a second gene of the second biological cell;
generating, utilizing the neural network machine learning model, a second individual perturbation feature vector, from the second digital image of the second biological cell exposed to the second gene knockout;
generating a predicted pairwise feature vector for the first biological cell individually exposed to the first gene knockout and the second biological cell individually exposed to the second gene knockout by combining the first individual perturbation feature vector and the second individual perturbation feature vector;
receiving a third digital image of a third biological cell exposed to a gene knockout pair comprising both the first gene knockout and the second gene knockout;
generating, utilizing the neural network machine learning model, a double perturbation pairwise feature vector from the third digital image of the third biological cell exposed to the gene knockout pair comprising both the first gene knockout and the second gene knockout;
generating a measure of biological interaction between the first gene knockout and the second gene knockout by comparing the predicted pairwise feature vector from the first digital image and the second digital image with the double perturbation pairwise feature vector from the third digital image, wherein the measure of biological interaction indicates a difference between biological cell response from exposure to the first gene knockout and the second gene knockout individually relative to biological cell response from exposure to the first gene knockout and the second gene knockout in combination;
generating an incomplete biological interaction matrix arranged according to a plurality of gene knockout pairs, wherein the incomplete biological interaction matrix comprises the measure of biological interaction for the gene knockout pair as an entry in the incomplete biological interaction matrix and further comprises additional measures of biological interactions as additional entries in the incomplete biological interaction matrix that correspond to additional gene knockout pairs of the plurality of gene knockout pairs;
generating, utilizing an active learning model that takes as inputs entries comprising the measure of biological interaction and the additional measures of biological interaction in the incomplete biological interaction matrix, predicted pairwise perturbation interaction scores corresponding to incomplete entries in the incomplete biological interaction matrix;
based on the predicted pairwise perturbation interaction scores, selecting additional gene knockouts for experimentation from the incomplete biological interaction matrix, wherein the additional gene knockouts for experimentation correspond to incomplete entries in the incomplete biological interaction matrix; and
performing a downstream experiment for a fourth biological cell by applying the additional gene knockouts selected from the incomplete biological interaction matrix to the fourth biological cell.
10 . The method of claim 9 , wherein:
receiving the first digital image comprises receiving a first captured image of the first biological cell with a first modified cell phenotype resulting from the first gene knockout of the first gene; and
receiving the second digital image comprises receiving a second captured image of the second biological cell with a second modified cell phenotype resulting from the second gene knockout of the second gene.
11 . The method of claim 9 , wherein determining the predicted pairwise feature vector for the first gene knockout and the second gene knockout comprises:
determining a first normalized feature vector from the first individual perturbation feature vector and a control feature vector and a second normalized feature vector from the second individual perturbation feature vector and the control feature vector; and
combining the first normalized feature vector and the second normalized feature vector to determine the predicted pairwise feature vector for the first gene knockout and the second gene knockout.
12 . The method of claim 9 , further comprising generating the double perturbation pairwise feature vector from the third digital image portraying the third biological cell exposed to a double gene knockout of the first gene and the second gene in the third biological cell.
13 . The method of claim 9 , wherein generating the incomplete biological interaction matrix comprises generating a matrix that includes pairwise perturbation experiment data corresponding to actual pairwise perturbations and predictions of measures of biological interactions corresponding to perturbation pairs.
14 . The method of claim 9 , further comprising generating, utilizing the active learning model that comprises a pairwise prediction model, the predicted pairwise perturbation interaction scores for individual gene knockouts and corresponding information gain predictions based on the incomplete biological interaction matrix, wherein the corresponding information gain predictions indicate an amount of potential increase in knowledge relative to the incomplete biological interaction matrix in response to a selection of the additional gene knockouts for experimentation.
15 . The method of claim 14 , wherein utilizing the active learning model comprises utilizing an active-matrix completion algorithm to select a first entry from a plurality of entry pairs of the incomplete biological interaction matrix based on the predicted pairwise perturbation interaction scores for the individual gene knockouts and the corresponding information gain predictions.
16 . A method comprising:
capturing, utilizing one or more digital cameras, a first digital image of a first biological cell exposed to a first perturbation, wherein the first perturbation comprises a first gene knockout of a first gene of the first biological cell or a first compound treatment of the first biological cell;
generating, utilizing a neural network machine learning model, a first individual perturbation feature vector, from the first digital image of the first biological cell exposed to the first perturbation;
capturing, utilizing the one or more digital cameras, a second digital image of a second biological cell exposed to a second perturbation, wherein the second perturbation comprises a second gene knockout of a second gene of the second biological cell or a second compound treatment of the second biological cell;
generating, utilizing the neural network machine learning model, a second individual perturbation feature vector, from the second digital image of the second biological cell exposed to the second perturbation;
generating a predicted pairwise feature vector for the first biological cell individually exposed to the first perturbation and the second biological cell individually exposed to the second perturbation by combining within a machine learning feature space, the first individual perturbation feature vector and the second individual perturbation feature vector;
capturing, utilizing the one or more digital cameras, a third digital image of a third biological cell exposed to a perturbation pair comprising both the first perturbation and the second perturbation;
generating, utilizing the neural network machine learning model, a double perturbation pairwise feature vector from the third digital image of the third biological cell exposed to the perturbation pair comprising both the first perturbation and the second perturbation;
generating a measure of biological interaction between the first perturbation and the second perturbation by comparing the predicted pairwise feature vector from the first digital image and the second digital image with the double perturbation pairwise feature vector from the third digital image, wherein the measure of biological interaction indicates a difference between biological cell response from exposure to the first perturbation and the second perturbation individually relative to biological cell response from exposure to the first perturbation and the second perturbation in combination;
generating an incomplete biological interaction matrix arranged according to a plurality of perturbation pairs, wherein the incomplete biological interaction matrix comprises the measure of biological interaction for the perturbation pair as an entry in the incomplete biological interaction matrix and further comprises additional measures of biological interactions as additional entries in the incomplete biological interaction matrix that correspond to additional perturbation pairs of the plurality of perturbation pairs;
generating, utilizing an active learning model that takes as inputs entries comprising the measure of biological interaction and the additional measures of biological interaction in the incomplete biological interaction matrix, predicted pairwise perturbation interaction scores corresponding to incomplete entries in the incomplete biological interaction matrix;
based on the predicted pairwise perturbation interaction scores, selecting additional perturbations for experimentation from the incomplete biological interaction matrix, wherein the additional perturbations for experimentation correspond to incomplete entries in the incomplete biological interaction matrix;
performing a downstream experiment for a fourth biological cell by perturbing, utilizing an experimental device, the fourth biological cell according to the additional perturbations selected from the incomplete biological interaction matrix; and
capturing, utilizing the one or more digital cameras, a fourth digital image of the fourth biological cell exposed to the additional perturbations selected from the incomplete biological interaction matrix.
17 . The method of claim 16 , wherein:
receiving the first digital image comprises receiving a first captured image of the first biological cell with a first modified cell phenotype resulting from the first gene knockout of the first gene; and
receiving the second digital image comprises receiving a second captured image of the second biological cell with a second modified cell phenotype resulting from the second gene knockout of the second gene.
18 . The method of claim 16 , wherein determining the predicted pairwise feature vector for the first perturbation and the second perturbation comprises:
determining a first normalized feature vector from the first individual perturbation feature vector and a control feature vector and a second normalized feature vector from the second individual perturbation feature vector and the control feature vector; and
combining the first normalized feature vector and the second normalized feature vector to determine the predicted pairwise feature vector for the first perturbation and the second perturbation.
19 . The method of claim 16 , further comprising generating the double perturbation pairwise feature vector from the third digital image portraying the third biological cell exposed to a double gene knockout of the first gene and the second gene in the third biological cell.
20 . The method of claim 16 , wherein generating the incomplete biological interaction matrix comprises generating a matrix that includes pairwise perturbation experiment data corresponding to actual pairwise perturbations and predictions of measures of biological interactions corresponding to perturbation pairs.