Abstract: The present disclosure relates to multifunctional molecules, including molecules according to formula (I): ([(B1)M-D-L1]Y—H1)O-G-(H2-[L2-E-(B2)K]W)P,??(I) wherein G, H1, H2, D, E, B1, B2, M, K, L1, L2, O, P, Y, and W are defined herein. The present disclosure also relates to methods of preparing and using such multifunctional molecules to identify encoded molecules capable of binding target molecules.

Abstract: Described are compositions and methods for inhibition of IRS1 gene expression. RNA interference (RNAi) agents for inhibiting the expression of IRS1 gene are described. The IRS1 RNAi agents disclosed herein may be targeted to cells, such as hepatocytes, for example, by using conjugated targeting ligands. Pharmaceutical compositions comprising one or more IRS RNAi agents optionally with one or more additional therapeutics are also described.

Abstract: Described are systems and methods for training a machine-learning model to generate image of biological samples, and systems and methods for generating enhanced images of biological samples. The method for training a machine-learning model to generate images of biological samples may include obtaining a plurality of training images comprising a training image of a first type, and a training image of a second type. The method may also include generating, based on the training image of the first type, a plurality of wavelet coefficients using the machine-learning model; generating, based on the plurality of wavelet coefficients, a synthetic image of the second type; comparing the synthetic image of the second type with the training image of the second type; and updating the machine-learning model based on the comparison.

Abstract: The present disclosure relates generally to machine learning techniques, and more specifically to machine learning techniques for generating synthetic spatial omics data based on histopathology image data. An exemplary system for generating synthetic spatial omics images comprises: one or more processors; a memory; and one or more programs, wherein the one or more programs are stored in the memory and configured to be executed by the one or more processors, the one or more programs including instructions for: receiving a histopathology image depicting a diseased region of interest of an input tissue sample; and generating a synthetic spatial omics image depicting one or more stained structures of interest within the diseased region of interest by inputting the histopathology image into a generator of a trained generative adversarial network (GAN) model.

Abstract: Described are systems and methods for training a machine-learning model to generate image of biological samples, and systems and methods for generating enhanced images of biological samples. The method for training a machine-learning model to generate images of biological samples may include obtaining a plurality of training images comprising a training image of a first type, and a training image of a second type. The method may also include generating, based on the training image of the first type, a plurality of wavelet coefficients using the machine-learning model; generating, based on the plurality of wavelet coefficients, a synthetic image of the second type; comparing the synthetic image of the second type with the training image of the second type; and updating the machine-learning model based on the comparison.

Abstract: Embodiments of the disclosure include systems and non-transitory computer readable media for analyzing microscopy images for developing machine learning models for disease modeling. Microscopy images are captured from cells of one or more exposure response phenotypes (ERPs) and further used to train machine learning models. Thus, trained machine learning models can distinguish between microscopy images captured from healthy and diseased samples.

Abstract: Described are systems and methods for training a machine-learning model to generate image of biological samples, and systems and methods for generating enhanced images of biological samples. The method for training a machine-learning model to generate images of biological samples may include obtaining a plurality of training images comprising a training image of a first type, and a training image of a second type. The method may also include generating, based on the training image of the first type, a plurality of wavelet coefficients using the machine-learning model; generating, based on the plurality of wavelet coefficients, a synthetic image of the second type; comparing the synthetic image of the second type with the training image of the second type; and updating the machine-learning model based on the comparison.

Abstract: The present disclosure relates generally to an autonomous cell imaging and modeling platform, and more specifically to machine-learning techniques for using microscopy imaging data to continuously study live biological cells. The autonomous cell imaging and modeling platform can be applied to evaluate various cellular processes, such as cellular differentiation, optimization of cell culture (e.g., in-plate cytometry), disease modeling, histopathology imaging, and genetic and chemical screening, using a dynamic universal imaging system. In some embodiments, the platform comprises a set of label-free computational imaging techniques, self-supervised learning models, and robotic devices configured in an autonomous imaging system to study positional and morphological characteristics in particular cellular substructures of a cell culture in an efficient and non-destructive manner over time.

Abstract: The present disclosure relates to bivalent or polyvalent linear initiator nucleic acids comprising initial building blocks and a coding region. The linear initiator nucleic acids may be used for the synthesis of an encoded compound to produce bivalent or polyvalent molecules.

Abstract: Described are compositions and methods for inhibition of glucokinase (GCK) gene expression and protein production. RNA interference (RNAi) agents for inhibiting the expression of GCK gene are described. The GCK RNAi agents disclosed herein may be targeted to cells, such as hepatocytes, for example, by using conjugated targeting ligands. Pharmaceutical compositions comprising one or more GCK RNAi agents optionally with one or more additional therapeutics are also described.

Abstract: The present disclosure relates generally to machine learning techniques, and more specifically to machine learning techniques for generating synthetic spatial omics data based on histopathology image data. An exemplary system for generating synthetic spatial omics images comprises: one or more processors; a memory; and one or more programs, wherein the one or more programs are stored in the memory and configured to be executed by the one or more processors, the one or more programs including instructions for: receiving a histopathology image depicting a diseased region of interest of an input tissue sample; and generating a synthetic spatial omics image depicting one or more stained structures of interest within the diseased region of interest by inputting the histopathology image into a generator of a trained generative adversarial network (GAN) model.

Abstract: The present disclosure relates to precursor molecules of DNA-encoded compounds, and methods of preparing thereof. In some aspects, provided herein are methods of synthesizing DNA-encoded compounds, and libraries thereof, from precursor molecules and positional building blocks.

Abstract: The present disclosure relates generally to biomarker discovery and patient stratification, and more specifically to machine learning techniques for discovering relevant biomarkers using data collected as part of the standard-of-care (SoC), which can be used to identify a relevant patient population for a therapeutic with a known mechanism of action (MoA). An exemplary method for predicting activity of a molecular analyte of a patient comprises: training a first module of a machine learning model based on a plurality of medical images of a first cohort; training a second module of the machine learning model based on one or more molecular analyte data sets obtained from a second cohort; receiving a medical image from the patient; and predicting, using the trained first and second modules of the machine learning model, the activity of the molecular analyte from the medical image of the patient.

Abstract: The present disclosure relates to a discovery platform including machine-learning techniques for using medical imaging data to study a phenotype of interest, such as complex diseases with weak or unknown genetic drivers. An exemplary method identifying a covariant of interest with respect to drug response phenotype (DRP) of a treatment is disclosed.

Abstract: The present disclosure relates generally to biomarker discovery and patient stratification, and more specifically to machine learning techniques for discovering relevant biomarkers using data collected as part of the standard-of-care (SoC), which can be used to identify a relevant patient population for a therapeutic with a known mechanism of action (MoA). An exemplary method for predicting activity of a molecular analyte of a patient comprises: training a first module of a machine learning model based on a plurality of medical images of a first cohort; training a second module of the machine learning model based on one or more molecular analyte data sets obtained from a second cohort; receiving a medical image from the patient; and predicting, using the trained first and second modules of the machine learning model, the activity of the molecular analyte from the medical image of the patient.

Abstract: Described are systems and methods for training a machine-learning model to generate image of biological samples, and systems and methods for generating enhanced images of biological samples. The method for training a machine-learning model to generate images of biological samples may include obtaining a plurality of training images comprising a training image of a first type, and a training image of a second type. The method may also include generating, based on the training image of the first type, a plurality of wavelet coefficients using the machine-learning model; generating, based on the plurality of wavelet coefficients, a synthetic image of the second type; comparing the synthetic image of the second type with the training image of the second type; and updating the machine-learning model based on the comparison.

Abstract: Described are systems and methods for training a machine-learning model to generate image of biological samples, and systems and methods for generating enhanced images of biological samples. The method for training a machine-learning model to generate images of biological samples may include obtaining a plurality of training images comprising a training image of a first type, and a training image of a second type. The method may also include generating, based on the training image of the first type, a plurality of wavelet coefficients using the machine-learning model; generating, based on the plurality of wavelet coefficients, a synthetic image of the second type; comparing the synthetic image of the second type with the training image of the second type; and updating the machine-learning model based on the comparison.

Abstract: An exemplary method for determining a sampling protocol for sampling tissue cores for a tissue microarray includes obtaining an initial plurality of tissue cores from an image of a tissue slide; selecting a first subset of the initial plurality of tissue cores based on a first candidate sampling protocol; inputting the first subset of the plurality of tissue cores into a machine learning model; evaluating the first candidate sampling protocol by evaluating a first output of the machine learning model; selecting a second subset of the initial plurality of tissue cores based on a second candidate sampling protocol; inputting the second subset of the plurality of tissue cores into the machine learning model; evaluating the second candidate sampling protocol by evaluating a second output of the machine learning model; and determining the sampling protocol based on the evaluation of the first candidate sampling protocol and the second candidate sampling protocol.

Abstract: A method for filtering out artifacts from a microscopic image of a tissue includes determining a plurality of frequency values corresponding to a plurality of pixels in the microscopic image of the tissue; grouping the plurality of pixels into a plurality of pixel clusters based on the plurality of frequency values corresponding to the plurality of pixels; identifying, from the plurality of pixel clusters, one or more pixel clusters corresponding to one or more artifacts in the microscopic image; and filtering the microscopic image by removing one or more regions in the microscopic image corresponding to the one or more pixel clusters corresponding to the one or more artifacts.

Abstract: An exemplary method for determining a sampling protocol for sampling tissue cores for a tissue microarray includes obtaining an initial plurality of tissue cores from an image of a tissue slide; selecting a first subset of the initial plurality of tissue cores based on a first candidate sampling protocol; inputting the first subset of the plurality of tissue cores into a machine learning model; evaluating the first candidate sampling protocol by evaluating a first output of the machine learning model; selecting a second subset of the initial plurality of tissue cores based on a second candidate sampling protocol; inputting the second subset of the plurality of tissue cores into the machine learning model; evaluating the second candidate sampling protocol by evaluating a second output of the machine learning model; and determining the sampling protocol based on the evaluation of the first candidate sampling protocol and the second candidate sampling protocol.