Abstract: The present disclosure relates in some aspects to methods and compositions for in situ analysis using nucleic acid complexes comprising a detectable label and a moiety that can be activated to extinguish signals of the detectable label. In some embodiments, the activatable moiety comprises a photosensitizer. The nucleic acid complexes may allow for improved detection and decreased signal carryover between detection cycles.

Abstract: The present disclosure relates in some aspects to methods and compositions for analyzing a biological sample, comprising performing rolling circle amplification of a circRNA in situ in a biological sample, thereby generating an RCA product comprising multiple complementary copies of the circRNA and detecting the RCA product in situ at a spatially localized position in the biological sample.

Abstract: A branched flow imaging system capable of fluorescence microscopy is disclosed, the system including a light source configured to emit excitation light, a sample slide configured to hold a sample to be imaged, a medium providing a potential with a correlation length greater than the excitation light wavelength, and a sensor configured to capture fluorescence emission light emitted by the plurality of fluorophores of the sample. The medium may be positioned such that the excitation light branches into a plurality of light channels that are incident upon the sample slide so that each of the light channels randomly excites an individual fluorophore molecule of the sample. The degree of randomness of the distribution of the light channels on the sample may be determined by a difference between the correlation length of the potential and the wavelength of the excitation light.

Abstract: Techniques are provided for facilitating network devices to obtain configuration updates from a central configuration repository. Configuration update information is received regarding a configuration update in a configuration repository. A data tree is updated based on the configuration update information. An identifier unique to the update is generated. A determination is performed that network device properties of a network device correspond to a set of network device properties indicated for the configuration update information. A notification indicating the availability of the configuration update is sent over one or more networks to the network device.

Abstract: The present disclosure in some aspects relates to methods and compositions for detecting and quantifying multiple analytes present in a biological sample by rolling circle amplification (RCA). In some aspects, the methods and compositions provided herein address issues associated with control of signal spot size and intensity for RCA products (RCPs) in a sample. In some aspects, provided herein are methods and compositions (e.g., probes and/or reaction mixtures) for slowing down RCA and/or decreasing the size of RCA products. In some embodiments, nucleotides or nucleotide analogs having a hydrophobic group (e.g., a hydrophobic modification on the base) are included in nucleotides for RCA and incorporated into the RCP product, leading to reduction of RCP size without the need of crosslinking an incorporated hydrophobic nucleotide or nucleotide analog to the RCP itself or another molecule.

Abstract: A cluster data replication system includes a plurality of network elements and controllers. The controllers form a cluster that is able to elect one of the controllers as a master controller with the others being follower controllers. The elected controller updates, responsive to being elected the master controller, state information in a system database of the elected controller to indicate that the elected one of the controllers is the master controller. The master controller includes one or more objects that are enabled in reaction to the state information, and which coordinate replication of changes to the data, system database, and state information from the master to the follower controllers. Each follower controller includes one or more objects able to, in reaction to the state information, disable initiation of the replication of changes to the data, system database and state information by the one or more objects in each follower controller.

Abstract: Techniques are provided for facilitating network devices to obtain configuration updates from a central configuration repository. Configuration update information is received regarding a configuration update in a configuration repository. A data tree is updated based on the configuration update information. An identifier unique to the update is generated. A determination is performed that network device properties of a network device correspond to a set of network device properties indicated for the configuration update information. A notification indicating the availability of the configuration update is sent over one or more networks to the network device.

Abstract: Techniques are provided for facilitating network devices to obtain configuration updates from a central configuration repository. Configuration update information is received regarding a configuration update in a configuration repository. A data tree is updated based on the configuration update information. An identifier unique to the update is generated. A determination is performed that network device properties of a network device correspond to a set of network device properties indicated for the configuration update information. A notification indicating the availability of the configuration update is sent over one or more networks to the network device.

Abstract: The present disclosure relates in some aspects to methods and compositions for analyzing a target nucleic acid, such as in situ detection of a region of interest in a polynucleotide in a cell or tissue sample. In some aspects, provided herein are circular probes (e.g., dumbbell probes) for analyzing a target nucleic acid, as well as methods comprising an enzymatic treatment to de-circularize unbound or non-specifically bound circular probes. Circular probes specifically bound to target nucleic acids remain intact during and after the enzymatic treatment and can be detected, e.g., via rolling circle amplification (RCA) of the circular probes and detection of the RCA products.

Abstract: The present disclosure in some aspects relates to methods and compositions for accurately detecting and quantifying multiple analytes present in a biological sample. In some aspects, the methods and compositions provided herein address one or more issues associated with the stability and/or size of nucleic acid structures, such as RCPs, in the biological sample without the use of exogenously added oligonucleotide compaction probes. In some embodiments, provided herein are methods involving the use of self-hybridizing hybridizing regions for compacting and/or stabilizing nucleic acid concatemers (e.g., RCPs). In some embodiments, dynamic inter-strand annealing between tandem units of an RCP is used for compaction and/or stabilization. In some embodiments, short palindromic regions in an RCP are used for compaction and/or stabilization.

Abstract: The present disclosure relates in some aspects to methods for analyzing a target nucleic acid in a biological sample. In some aspects, the methods involve the use of a set of oligonucleotides, for example a set of two or more oligonucleotides, wherein one or more oligonucleotides comprises one or more photoreactive nucleotides, for analyzing target nucleic acids. In some aspects, the presence, amount, and/or identity of a target nucleic acid is analyzed in situ. Also provided are oligonucleotides, sets of oligonucleotides, compositions, and kits for use in accordance with the methods.

Abstract: The present disclosure relates in some aspects to proteins and nucleic acids for probing analytes in a biological sample. In some embodiments, disclosed herein is a method in which detection probes (e.g., fluorescently labeled detection probes) may comprise a sequence of nucleobases on a synthetic backbone, the detection probes therefore generating a greater signal than reference detection probes having the same sequence of nucleobases on a sugar-phosphate backbone.

Abstract: A cluster data replication system includes a plurality of network elements and controllers. The controllers form a cluster that is able to elect one of the controllers as a master controller with the others being follower controllers. The elected controller updates, responsive to being elected the master controller, state information in a system database of the elected controller to indicate that the elected one of the controllers is the master controller. The master controller includes one or more objects that are enabled in reaction to the state information, and which coordinate replication of changes to the data, system database, and state information from the master to the follower controllers. Each follower controller includes one or more objects able to, in reaction to the state information, disable initiation of the replication of changes to the data, system database and state information by the one or more objects in each follower controller.

Abstract: A cluster file replication system is provided. Each controller of the plurality of controllers is configured to access a filesystem having a plurality of files including a system database of a controller having state information of the plurality of controllers. Each controller is further configured to have one or more service agents. The one or more service agents of each controller is configured to respond to one of the plurality of controllers becoming a master controller of the cluster. The one or more service agents of each controller is configured to set up one or more objects that react to the state information and coordinate replication of changes to the files, system database and state information from the master controller to follower controllers in the cluster. The one or more objects on each of the follower controllers is supportive of the follower controllers receiving the changes but disabled from initiating the replication. A method for cluster file replication is also provided.

Abstract: Provided herein are methods and compositions for the sequencing of long nucleic acids, such as DNA. The methods and compositions are suited for the spatial labeling and sequencing of long nucleic acid molecules.

Abstract: A method includes receiving a single request to configure a continuous route tracer (CRT) between a first plurality of network devices and a second plurality of network devices and configuring, by a processing device of a control server, the CRT between the first plurality of network devices and the second plurality of network devices. The method further includes receiving a plurality of probe reports corresponding to a plurality of CRT probes sent between the first plurality of network devices and the second plurality of network devices and analyzing the reports to detect one or more anomalies corresponding to a network comprising the first plurality of network devices and the second plurality of network devices. The method further includes providing the one or more anomalies for display.

Abstract: The present disclosure relates to processes for inverting oligonucleotide probes in an in situ synthesized array. These processes can be used to reverse the orientation of probes with respect to the substrate from 3?-bound to a substrate to 5?-bound to another substrate. These processes can also be used to reduce or eliminate the presence of truncated probe sequences from an in situ synthesized array. These processes can preserve the original patterns of the synthesized oligonucleotide after the inversion. These process can be achieved via the formation of a hydrogel layer in-between a donor substrate and an acceptor substrate through a polymerization reaction forming the hydrogel layer.

Abstract: The present disclosure provides methods, devices and systems that enable determination of spatial information of biological molecules by reacting the biological molecules with a zipcode array. In some examples, the zipcode array may code for the spatial positions of biological molecules attached to distinct positions on the zipcode array. In some examples, the spatial positions are 2-dimensional. In some cases, the spatial positions are 3-dimensional. In some examples, the present disclosure provides methods to detect spatial gene expression. In some examples, the present disclosure provides methods to detect spatial distribution of proteins.

Abstract: Provided herein are methods and compositions for analyzing epigenetic modifications of genomes. The methods and compositions are suited for complete epigenome sequencing of any modification for which an antibody or an affinity binding agent has been developed.

Abstract: A cluster file replication system is provided. Each controller of the plurality of controllers is configured to access a filesystem having a plurality of files including a system database of a controller having state information of the plurality of controllers. Each controller is further configured to have one or more service agents. The one or more service agents of each controller is configured to respond to one of the plurality of controllers becoming a master controller of the cluster. The one or more service agents of each controller is configured to set up one or more objects that react to the state information and coordinate replication of changes to the files, system database and state information from the master controller to follower controllers in the cluster. The one or more objects on each of the follower controllers is supportive of the follower controllers receiving the changes but disabled from initiating the replication. A method for cluster file replication is also provided.