Verily Life Sciences LLC

X Development LLC

Palo Alto Research Center Inc.

Jason Donald Thompson

Vikram Singh Bajaj

Andrew Homyk

Mark West Askew

Eric Peeters

Frank D Russo

Victor Marcel Acosta

Jerrod Joseph Schwartz

Andrew J Conrad

David Kalman Biegelsen

Jengping Lu

Andrew Jason Conrad

Mark Askew

Eugene Michael Chow

Jonathan Alexander Ross

Russell N Mirov

Gregory Lewis Whiting

Janos Veres

Vasiliki Demas

Joshua Simon Klein

Martin F Schubert

Michael Jason Grundmann

Tamara Troy

Tammo Spalink

Ian Peikon

Nicholas Casavant

Yu Tanouchi

Nicholas Ruggero

Chirath Thouppaurachchi

Russell Norman Mirov

A system for collecting data for assessment of cardiovascular function includes a plurality of monitoring devices coupled to different respective body parts. Each monitoring device is configured to measure a respective signal at the respective body part in response to cardiovascular activity. The respective signal includes a cardiovascular component attributable to the cardiovascular activity and an artifact component not attributable to the cardiovascular activity. When the monitoring devices measure the respective signals simultaneously over a same time period, the cardiovascular components are correlated, and the artifact components are not correlated. The system also includes a controller configured to: identify the cardiovascular components included in the signal measurements, according to the correlation of the cardiovascular components; reject the artifact components included in the signal measurements, according to the non-correlation of the artifact components; and determine cardiovascular information from the identified cardiovascular components for an assessment of cardiovascular function.

Cardiovascular monitoring using combined measurements

Systems and methods are provided for detecting the flow of blood or other fluids in biological tissue by illuminating the biological tissue with two or more beams of coherent light and detecting responsively emitted light. A difference in wavelength, coherence length, beam divergence, or some other property of the beams of illumination causes the beams to preferentially scatter from, be absorbed by, or otherwise interact with respective elements of the biological tissue. Flow properties in one or more regions of the biological tissue (e.g., a region with which both beams of light preferentially interact, a region with which only one of the beams preferentially interacts) could be determined based on detected responsively emitted light from the biological tissue. Variations in speckle patterns over time and/or space, Doppler shifts, or some other properties of the detected light could be used to determine the flow properties.

Applications of hyperspectral laser speckle imaging

A method for modulating a response signal includes introducing functionalized particles into a lumen of subsurface vasculature, wherein the functionalized particles are configured to interact with one or more target analytes present in blood circulating in the subsurface vasculature; and non-invasively detecting the one or more target analytes. A response signal, which may include a background signal and an analyte response signal related to interaction of the functionalized particles with the one or more target analytes, is transmitted from the subsurface vasculature. A modulation configured to alter the response signal such that the analyte response signal is affected differently than the background signal may be applied to a portion of subsurface vasculature. Analyte detection may be achieved by differentiating the analyte response signal from the background signal.

Modulation of a response signal to distinguish between analyte and background signals

Methods, systems, and apparatuses, including computer programs encoded on a computer storage medium, can be implemented to perform certain actions. The actions can include maintaining biological data related to multiple biological systems in a first format in a data repository, receiving a first selection of a biological system of the multiple biological systems for constructing a model that simulates a behavior of the biological system, retrieving a subset of data of the biological data that is associated with the first selection of the biological system, receiving a second selection of a modeling technique of the multiple modeling techniques for constructing the model, compiling the subset of biological data into configuration data of a second format that is specific to the modeling technique and that is different from the first format, and generating the model using the modeling technique and the configuration data.

Biological modeling framework

A bipartite graph structure is utilized to better store data. The bipartite graph structure may be used in a biochemical database to efficiently store a variety of molecules and processes that might occur between the molecules. Molecules are represented as molecule nodes, which may have metadata fields including a molecule name, a molecule type, a molecular formula, a sequence, a molecular charge, a set of molecular properties, and a set of component molecules. Processes operating on the molecules are represented by process nodes, which may have metadata fields including a process name, a set of process roles, a set of process properties, and a set of sub-processes. Edges, called roles, each associate a molecule node with a process node and represent the role the associated molecule plays in the associated process. The roles may contain metadata identifying the role type and the stoichiometry coefficient of the molecule in the process.

Bipartite graph structure

A method for allocating resources among multiple sub-models in a simulation of a biological cell is described herein. The method receives an initial state dataset including initial aggregate resources in a plurality of sub-models, which make up a whole cell model. The method calculates, at a first time step, an outcome of each of the sub-models, which includes a local production, a local consumption and local net value of at least one resource shared between at least two sub-models. The method calculates a subsequent state dataset based on the outcome of each of the sub-models. The subsequent state dataset includes subsequent aggregate resources, the local production, the local consumption and local net value. The method determines, at a second time step, a second outcome of each of the plurality of sub-models based on the subsequent aggregate resources and the local production, local consumption and local net value.

Dynamic coordinating framework for model cell simulations

A system is described for constructing a biological simulation using inputs from a knowledge base data structure and one or more templates. The knowledge base data structure comprises a set of entries representing distinct molecules and chemical reactions specific within the cell. Each template defines a sub-model program specification and a set of sub-model parameters to further characterize the sub-model specification. A graphical user interface is presented on a display for a user to view and select a templates and to assign information from the knowledge base to the selected template. From the graphical user interface, the user selects multiple templates to be included in the simulation and information from the knowledge base generally describing the cell. Based on the information selected from the graphical user interface, a compiler generates a simulation configuration data file comprising computer code capable of being executed by a simulation engine.

Data structure, compilation service, and graphical user interface for rapid simulation generation

A method for simulating a biochemical environment utilizes a heterogeneous process model, which evaluates both a flux balance analysis and one or more detailed models each on a different but overlapping sets of molecules in the biochemical environment. The heterogeneous process model evaluates the flux balance analysis based on a stoichiometric matrix, a flux vector including initial internal exchange flux values, and an objective function. The heterogeneous process model evaluates the one or more detailed models based on an initial set of molecule concentrations and a plurality of detailed model parameters. The results are then used to update the exchange fluxes and molecules concentrations. The process is repeated thereby integrating the results of the flux balance analysis with the one or more detailed models.

Heterogeneous method for modelling a biochemical environment

A method for analyzing a bipartite graph data structure to condense reaction pathways of a metabolic network is described herein. A cell's metabolic network is structured as a bipartite graph, with molecule nodes representing the molecules within metabolism and edges connecting molecule nodes representing chemical reactions or processes. Molecule nodes within the bipartite graph are categorized according to the number of edges leading into and out of each node. If the structure of the bipartite graph indicates that the molecule node does not contribute to flux value solutions of a mathematical model of the metabolic network, then the node and its connected reaction pathway is blocked or removed from the bipartite graph. Thus the complexity of the bipartite graph may be reduced, and crucial nodes and pathways identified.

Method for analyzing and optimizing metabolic networks

Systems and methods are provided for detecting the depth, flow rate, and other properties of regions of blood flow in biological tissue by illuminating the biological tissue with beams of coherent light and detecting responsively emitted light. This includes detecting lights emitted from the tissue having a plurality of respective different exposure times. The relationship between the intensity of the received light and the exposure times is determined and used to determine the depth, flow velocity, or other properties of regions of flow within the biological tissue. This can include determining a spatial and/or temporal contrast of the received light intensity. Determining the depth of a region of flow can include comparing determined properties of light received from the tissue at two different polarizations. Determining the depth of a region of flow can include comparing determined properties of light received from the tissue at two different locations.

Methods for depth estimation in laser speckle imaging

Systems are provided for detecting the flow of blood or other fluids in biological tissue by illuminating the biological tissue with a coherent light source and detecting time-varying patterns of constructive and destructive interference in light received from portions of the biological tissue by an imager. The movement of blood cells and other light-scattering elements in the biological tissue causes transient, short-duration changes in light emitted from portions of the biological tissue proximate to the moving blood cells or other scatterers. High-frequency sampling or other high-bandwidth processing of light intensities detected by an imager could be used to determine the flow of blood or other fluids at a plurality of points in the biological tissue, to detect and/or localize a tumor in the biological tissue, to determine the location, pattern, width, or other properties of vasculature in the biological tissue, or to provide information for some other application(s).

Applications of vasculature mapping using laser speckle imaging

The behavior and/or internal activities of a microorganism can be simulated using a model of the microorganism. Such simulations can be used to determine the efficacy of treatments, disinfectants, antibiotics, chemotherapies, or other methods of interacting with the microorganism, or to provide some other information about the microorganism. Systems and methods are provided herein for fitting, refining, or otherwise improving such models in an automated fashion. Such systems and methods include performing whole-cell experiments to determine a correspondence between the predictions of such models and the actual behavior of samples of the microorganism. Such systems and methods also include, based on such determined correspondences, directly assessing determined discrete sets of properties of the microorganism and/or of constituents of the microorganism and updating parameters of the model corresponding to the properties of the discrete set such that the overall accuracy of the model is improved.

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Palo Alto, CA, United States of America

Jason Donald Thompson