A method for extending a depth of field of a nucleic acid sequencer may comprise optimization steps which are repeated one or more times, in which a result of passing light through an objective lens and a mask is compared with an ideal result, and any discrepancy is used to update the mask. Such a mask may be incorporated into a nucleic acid sequencer which adds fluorescent tags to nucleic acid sites and then detect light emitted from the fluorescent tags, thereby extending the sequencer's depth of field.
G01N 21/27 - Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection
2.
ALPHA-MODIFIED NUCLEOSIDE TRIPHOSPHATES AND METHOD FOR THEIR SYNTHESIS
A nucleoside triphosphate analogue including a sugar, a nucleobase coupled to the sugar, a triphosphate group coupled to the sugar, a heteroatom coupled to an alpha phosphate of the triphosphate group, and a first substituent coupled to the heteroatom. The heteroatom may be selected from the group consisting of oxygen, nitrogen, and carbon. The first substituent may include at least one of an alkyl chain or a polymer. The nucleoside triphosphate analogue may have the formula (I).
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 19/20 - Purine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
3.
SYSTEMS AND METHODS OF DETERMINING A NUCLEIC ACID SEQUENCE BASED ON MUTATED SEQUENCE READS
Described herein are methods and systems for determining a sequence of a nucleic acid template by removing mutations found in a mutated sequence read. In some embodiments, methods and systems include steps of aligning unmutated sequence reads of a nucleic acid template to mutated sequence reads, and determining a most probable sequence of the nucleic acid template and a per-base accuracy score correlated with the probability that the base matches with the nucleic acid template, thereby determining the sequence of the nucleic acid template.
A method and system for polynucleotide sequencing and sequence assembly using a k-mer graph approach is disclosed. The methods may include receiving a sample comprising a nucleic acid sequence, fragmenting the sample into a plurality of shorter sequences, and aligning the shorter sequences to a reference genome to identify a k-mer sequence. The systems may include a processor, a memory, and a storage device configured to store the reference genome and the sample. The processor may be configured to execute the steps of the method, including aligning shorter sequences to a reference genome.
Aptamer detection techniques are described that may include aptamer modification to facilitate incorporation of adapter sequences. In an embodiment, a 3' end of an aptamer may be modified by deprotection and subsequent ligation to the deprotected 3' end or extension of the deprotected 3' end. The modifications at the 3' end of the adaptor may include adaptor sequences used for library preparation of a sequencing library.
Automated methods conducted in a sequencing flowcell, and kits for reusing a flowcell, are provided herein. In some examples, an automated method conducted in a sequencing flowcell may include, at a surface of the sequencing flowcell coupled to a first moiety, using a reagent to decouple a first complex from the first moiety. In some examples, the first complex may include a second moiety which couples to the first moiety and a polynucleotide coupled to the second moiety. In some examples, the method may further include using a nuclease to polynucleotides in the sequencing flowcell. The method may include, after using the reagent and after using the nuclease, coupling a second complex to the first moiety. The second complex may include a third moiety which couples with the first moiety and an oligonucleotide coupled to the third moiety.
The technology relates in part to estimating fetal fraction in non-invasive prenatal testing using one or more fragmentomics parameters. In some aspects, the technology relates to estimating fetal fraction according to nucleic acid fragment lengths and sequence motif frequencies.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
In an example method, a grafting solution is applied to a patterned substrate using a liquid-phase thin-film deposition technique. The patterned substrate includes a lane surrounded by, or a plurality of depressions separated by interstitial regions; and a polymer in the lane or in each of the plurality of depressions. The polymer is functionalized with a first click reaction moiety. The grafting solution includes a solvent; a polymer matrix material dissolved in the solvent; and primers of a primer set dissolved in the solvent, each of the primers being terminated with a second click reaction moiety. The applied grafting solution is dried. During drying, a solid polymer matrix is formed and at least some of the primers attach to the polymer i) via the first and second click reaction moieties and ii) in at least a portion of the lane or in at least some of the plurality of depressions.
A mixture of clustered and unclustered magnetic beads are generated from magnetic beads i) functionalized with a first primer of a primer set and ii) contained in a suspension. Each clustered bead includes a first amplicon attached to the first primer and a 5'-tagged second amplicon hybridized to the first amplicon. A 5'-tag of the second amplicon is a binding pair first member. Coated non-magnetic beads (including a binding pair second member coating, and having a diameter that is at least ten times larger than each magnetic bead) are introduced into the suspension. The clustered magnetic beads bind to at least some of coated non-magnetic beads to form bead-on-bead complexes. The unclustered magnetic beads remain free in the suspension, and are separated from the suspension. The 5'-tagged second amplicon is dehybridized from the first amplicon to generate single stranded clustered magnetic beads, which are then separated from the suspension.
This disclosure describes methods, non-transitory-computer readable media, and systems that can identify and apply a temperature weight to a pathogenicity prediction for an amino-acid variant at a particular protein position to calibrate and improve an accuracy of such a prediction. For example, in some cases, a variant pathogenicity machine-learning model generates an initial pathogenicity score for a protein or a target amino acid at a particular protein position based on an amino-acid sequence of the protein. The disclosed system further identifies a temperature weight that estimates a degree of certainty for pathogenicity scores output by the variant pathogenicity machine-learning model. To generate such a weight, the disclosed system can use a new triangle attention neural network as a temperature prediction machine-learning model. Based on the temperature weight and the initial pathogenicity score, the disclosed system generates a calibrated pathogenicity score for the target amino acid at the particular protein position.
The determination of pharmacogenomics gene star alleles using high-throughput targeted genotyping includes obtaining input genetic sequence variation data from a high-throughput genotyping platform based on a pharmacogenomic genotyping of a sample, applying a Bayesian graphical model to determine a plurality of different star allele calls corresponding to the sample, and providing a respective quality score for each star allele call of the plurality of different star allele calls. For instance, the application of the Bayesian graphical model uses multi-solution integer programming to explore a model space of the Bayesian graphical model in a first phase that includes structural variant candidate identification and a second phase that includes star allele candidate identification based on the structural variant candidate identification, to determine the plurality of different star allele calls.
Array-based targeted copy number detection, for instance detection on contaminated and/or variable concentration samples, includes obtaining a collection of intensity signals from assays of a set of input samples, performing a cross-sample calibration on the intensity signals based on reference sample(s), which calibration includes constructing a reference signal distribution based on intensity signals of the reference sample(s) and for one or more input samples calibrating a set of intensity signals corresponding to the input sample based on the reference signal distribution, determining, for the one or more input samples, and from a respective one or more calibrated sets of intensity signals corresponding to the one or more input samples, a respective at least one aggregated calibrated signal from targeted genomic region(s) to produce a collection of aggregated calibrated signals, and detecting variant(s) in the targeted genomic region(s) based on the collection of aggregated calibrated signals.
In an example of a method for making a flow cell, a sacrificial layer is deposited over a substrate including depressions separated by interstitial regions. The sacrificial layer is dry etched from the depressions, and the sacrificial layer remains on the interstitial regions. A functionalized layer is deposited over the depressions and over the sacrificial layer. The sacrificial layer is removed from the interstitial regions, which also removes the functionalized layer that overlies the interstitial regions.
The present invention includes methods and computer programs for use in the detection preeclampsia and/or determining an increased risk for preeclampsia in a pregnant female, the methods including identifying in a biosample obtained from the pregnant female cell-free DNA signals, including concentration, fetal fraction, and fragment size distribution. These methods provide for the identification of patients at risk of preeclampsia in the first trimester of pregnancy.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
G16H 50/00 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
15.
DETERMINING AND REMOVING INTER-CLUSTER LIGHT INTERFERENCE
This disclosure describes embodiments of methods, systems, and non-transitory computer readable media that accurately estimates the crosstalk from an adjacent cluster of oligonucleotides onto a target cluster of oligonucleotides and removes or reduces the crosstalk emitted by the adjacent cluster of oligonucleotides from the target cluster of oligonucleotides. For instance, the disclosed systems can detect the intensity values for a target cluster and the adjacent cluster. Based on the intensity values of the adjacent cluster, the disclosed systems can determine an inter-cluster-interference metric that estimates the crosstalk emitted from the adjacent cluster. The disclosed systems can remove the inter-cluster-interference metric from the intensity value of the target cluster and generate modified intensity values for the target cluster.
Improved copy number variant (CNV) calling in a genomic sequence, and potential recovery, includes (i) obtaining genetic sequence variant data that includes records indicating structural variant(s) (SVs) and records indicating CNV(s) in the genomic sequence, (ii) determining, based on an initial CNV indicated in the genetic sequence variant data and on initial SV(s) indicated in the genetic sequence variant data, an SV-informed CNV call as an updated version of the initial CNV, where the determining uses information from the initial SV(s) to determine a start breakpoint position and an end breakpoint position for the SV-informed CNV call, at least one of the start breakpoint position and end breakpoint position being updated, informed by the initial SV(s), in comparison to a corresponding start breakpoint position and/or end breakpoint position of the initial CNV, and (ii) writing the determined SV-informed CNV call as record(s) in a genetic sequence variant data file.
METHODS OF MODIFYING METHYLCYTOSINE OR DERIVATIVE THEREOF USING A PHOTOREDOX REACTION, AND METHODS OF USING THE SAME TO DETECT THE METHYLCYTOSINE OR DERIVATIVE THEREOF IN A POLYNUCLEOTIDE
Disclosed herein are methods of using photoredox reactions to modify 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC), 5-formlcytosine (5-fC), or 5-carboxylcytosine (5-caC) in a polynucleotide. In some examples, a photoredox reaction is used to install a functional group at the 5-position of the 5-caC, wherein the installed functional group further reacts with the 5-caC to form a product having at least two rings. In other examples, a photoredox reaction is used to install a functional group at the 5-methyl group of the 5-mC, wherein the installed functional group further reacts with the 5-mC to form a product having at least two rings. In other examples, a photoredox reaction is used to oxidize the 5-mC or 5-hmC to 5-fC; and a functional group at the 5-position of the 5-fC, wherein the installed functional group further reacts with the 5-fC to form a product having at least two rings.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
Systems, methods, and apparatuses are described herein. For instance, a detection apparatus may comprise memory and at least one processor. The detection apparatus may be configured to obtain an image comprising at least one feature and a plurality of fiducials. The plurality of fiducials may be arranged in a pattern. The detection apparatus may be configured to determine a plurality of sub-regions of the image. Each sub-region comprises a subset of the fiducials comprised in the image. The detection apparatus may be configured to perform a geometric transform on each sub-region to generate a respective local transform associated with each sub-region. The detection apparatus may be configured to register respective locations of the fiducials comprised in the image based on the respective local transform associated with each sub-region. A size of each sub-region may be selected such that each sub-region is substantially invariant to stage jitter.
Systems and methods for identifying a host of an AMR marker from one or more samples are provided, which include obtaining short-read sequence data derived from one or more samples; identifying one or more AMR markers from the short-read sequence data to obtain short-read metrics, the short-read metrics comprising quantitative metrics such as RPKM, median depth, read count, or others of any one or more of the AMR markers identified in the short-reads; obtaining one or more reference sequence data; identifying one or more AMR markers from the reference sequence data to obtain reference metrics, the reference metrics comprising quantitative metrics such as RPKM, median depth, read count, or others of any one or more of the AMR markers identified in the reference sequence; identifying a host of the one or more AMR markers in the sample when average ratios between the short-read metrics and the reference metrics are below a threshold ratio.
Described herein are methods of removing false positive uracils due to the deamination of unmethylated cytosines in assays using engineered cytosine deaminases to deaminate methylated cytosines, the methods utilizing enzymes that discriminate against uracil residues, such as for example, uracil-intolerant polymerases, uracil DNA glycosylase (UDG), and/or USER™ (Uracil-Specific Excision Reagent) enzyme, to remove false positive uracil residues from cytidine deaminase mediated methylation sequencing assays.
Embodiments of the present disclosure relate to nucleotides with 3' allyl blocking groups. Also provided herein are methods of sequencing using nucleotides with 3' allyl blocking groups described herein, and sequencing kits.
C40B 50/14 - Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
23.
SPATIAL TRANSCRIPTOMICS LIBRARY PREPARATION MATERIALS AND METHODS
The present disclosure relates, in general, to methods for improving preparation of a spatial transcriptomics RNA, library, for example a mRNA library, by improving capture of RNA transcript information from a tissue sample in situ. The spatial transcriptomics library from a tissue sample is useful to determine a genetic profile and help diagnose a person who has or is at risk of having a disease, such as cancer, genetic disease, autoimmune disease, and other indications, and improve treatment of the subject.
The present disclosure relates, in general, to materials and methods for improving RNA capture in situ from tissue samples and improved methods for synthesizing cDNA from the captured RNA.
Flow cell assemblies and related systems and methods are disclosed. An apparatus includes a flow cell assembly having a body, a first laminate, a second laminate, and a flow cell. The body carries a flow cell inlet gasket, a flow cell outlet gasket, and an outlet gasket. The body includes a fluidic aperture. The first laminate is coupled to the body and forms a first fluidic channel between the flow cell outlet gasket and the fluidic aperture. The second laminate is coupled to the body and forms a second fluidic channel between the fluidic aperture and the outlet gasket. The flow cell is supported by the body and includes a channel having a flow cell inlet and a flow cell outlet. The flow cell inlet is fluidly coupled to the flow cell inlet gasket and the flow cell outlet is fluidly coupled to the flow cell outlet gasket.
A method for modifying an interstitial surface separating recesses from one another can include flowing a first fluid over the interstitial surface and into the recesses, such that the interstitial surface is substantially coated with the first fluid and the recesses are substantially filled with the first fluid; and while the first fluid remains within the recesses, replacing the first fluid coating the interstitial surface with a second fluid comprising a reagent.
Multivalent assemblies for target hybridization are described. The multivalent assemblies include oligonucleotide sets that hybridize to a target nucleic acid to permit capture of the target nucleic acid. In an embodiment, the multivalent assemblies are heteromultivalent such that the oligonucleotide sets include different oligonucleotides that bind to different regions of the target nucleic acid.
The present application relates to compositions and methods for sequencing by synthesis. A blocking group of a nucleotide may be removed by a transition metal catalyst, the transition metal catalyst activated by a non-reducing ligand and a reducing agent.
Systems, methods, and apparatus are described herein for aggregating genome data into bins with summary data at various levels. As described herein, a computing device may be configured to receive genome data associated with a genome. The computing device may be configured to generate an aggregate file using the received genome data. The aggregate file may include a plurality of bins at a plurality of depths. The computing device may be configured to determine summary data for respective reads associated with one or more respective portions of the genome covered by respective bins of the plurality of bins. The computing device may be configured to store the summary data for the respective reads in respective bins of the plurality of bins. The computing device may be configured to display a portion of the summary data in response to a selection of a genomic region by a user.
The technology disclosed is directed to context-dependent base calling. The technology disclosed describes a system including memory storing k-mer-specific centroids for k-mers. The k-mer-specific centroids are learned by training a base calling pipeline to represent base calls of an already base called sequence in k-mer-specific time series, transform the k-mer-specific time series into predicted k-mer-specific centroids, merge the predicted k-mer-specific centroids on a sequencing cycle-by-sequencing cycle basis to generate predicted per-sequencing cycle intensity values, determine a training loss (e.g., a transformation loss) based on comparing the predicted per-sequencing cycle intensity values against known intensity values of the base calls, update the predicted k-mer-specific centroids based on the determined training loss, and store the updated centroids as the k-mer-specific centroids. The system also includes runtime logic that uses the k-mer-specific centroids to base call bases in a yet-to-be base called sequence in dependence upon k-mer context.
An RNA sequencing library preparation process that that utilized transposition with or with a template switch oligonucleotide to generate the libraries having UMIs and spatial barcode information, and methods for improving RNA library preparation from tissue samples using template switching and thermal amplification to improve RNA library quality.
This application relates to methods of denaturing double-stranded DNA (dsDNA). In some examples, the methods utilize dried sodium hydroxide. In some examples, the method includes loading dsDNA into a first portion of a cartridge, wherein the second portion of the cartridge contains sodium hydroxide in a dry form; and mixing the dsDNA with the sodium hydroxide, thereby denaturing the dsDNA.
Apparatus and methods for transferring and delivering dried reagents are disclosed. In accordance with an implementation, an apparatus includes a carrier comprising a carrier body and a plurality of pins extending from the carrier body. The pins are aligned and oriented to correspond to a plurality of wells in a well plate. Each of the plurality of pins has an end surface, opposite the carrier body and a dried reagent is retained on the end surface of at least a portion of the plurality of pins.
Dual channel sipper assemblies and related methods are disclosed. A reagent assembly for a sequencing platform includes a reagent cartridge having a first container including a container body and an open end. The container body defines a reagent chamber containing a liquid reagent. A cover is disposed over the open end and the cover includes a pressure and reagent port fluidly coupled to the reagent chamber. A sipper is adapted for piercing the cover of the reagent cartridge through the pressure and reagent port to both pressurize the reagent chamber and to aspirate liquid reagent from the reagent chamber. The sipper includes a first lumen and a second lumen. The first lumen is to deliver pressurized fluid to the reagent chamber. The second lumen is to aspirate liquid reagent from the reagent chamber.
Biological samples on multiple surfaces of a support structure may be imaged using a machine comprising a lens, a flow cell and a controller. Such a machine may capture light emitted from nucleic acids disposed on first and second surfaces of the flow cell when the lens is, respectively, at first and second distances from the flow cell. In such a machine, the lens may be immersed in a first fluid, and the first and second surfaces of the flow cell may be separated by a second fluid. Additionally, in such a machine, differences between marginal and axial light rays in the field of view of the lens may be substantially equal when the lens is at the first and second distances from the flow cell.
The present application relates to palladium catalyst composition and uses in sequencing by synthesis. In particular, the Pd catalyst composition comprises one or more macrocycles (e.g., cyclodextrin or analogs thereof) as additives for improving thermal or oxidative stability of the active Pd(0) species.
The present disclosure relates, in general, to methods of preparing a spatial proteome and/or transcriptome sequencing library. The spatial proteome and/or transcriptome sequencing library from a biological sample is useful, in some aspects, to determine a genetic profile and help diagnose a subject who has or is at risk of having a disorder, and improve treatment of the subject.
Library preparation systems and methods are disclosed. In an implementation, a modular bay for preparing a library of samples for sequencing, the modular bay comprising a contact dispenser and a working area comprising a working plate receptacle adapted to receive a working plate, a thermocycler, a magnet, and a drawer. The drawer comprising a consumables area adapted to receive a sample plate adapted to contain a sample, and a plurality of consumables for interacting with the sample in the working plate. The contact dispenser is linearly movable in a longitudinal direction between the consumables area and the working area, such that the contact dispenser is configured to (i) move the sample from the sample plate in the consumables area to the working plate in the working area, and (ii) move the plurality of consumables between the consumables area and the working plate in the working area.
An example of a flow cell includes a substrate; a plurality of reactive regions spatially separated from one another across the substrate; and a plurality of independently removable coatings respectively positioned over each of the plurality of reactive regions. Each of the plurality of reactive regions includes a polymeric hydrogel layer; and a reactive entity attached to the polymeric hydrogel layer. At least one of the independently removable coatings is a composite that includes a thermo-responsive polymer and a photo-thermal additive.
An example of a flow cell includes a substrate; a plurality of reactive regions spatially separated from one another across the substrate; and a plurality of independently removable coatings respectively positioned over each of the plurality of reactive regions. Each of the plurality of reactive regions includes a polymeric hydrogel layer; and a reactive entity attached to the polymeric hydrogel layer. At least one of the independently removable coatings is a gas-dissolvable coating.
An example of a flow cell includes a substrate having depressions separated by interstitial regions; a polymeric hydrogel positioned within each of the depressions; and a plurality of transposome complexes immobilized within each of the depressions by a biotin-containing linker. In this example, each of the plurality of the transposome complexes is of a single type including a transposon end with a portion of a transferred strand hybridized to a portion of a non-transferred strand, wherein the transferred strand includes a first amplification domain and is free of an index sequence.
Reusable flow cells for sequencing which exhibit signal intensity retention over numerous use cycles, the active surface of which contains reactive sulfur moieties for reversible primer binding, methods of using such flow cells, reagents therefor, and kits containing the same.
Methods for on-flow cell selective capture and enrichment of clustered beads, general capture strategies on bead mobility on flow cell surfaces, sorting clustered and unclustered beads, and flow cell reusability for bead immobilization onto flow cells.
Disclosed herein are methods and compositions that utilize boranes on solid supports. The methods and compositions can be used to detect methylation on polynucleotides. In some examples, a method includes oxidizing any 5-methylcytosine (5-mC) or 5-hydroxymethylcytosine (5-hmC) on a polynucleotide to 5-carboxylcytosine (5-caC) or 5-formylcytosine (5-fC). The method may include reducing the 5-caC or 5-fC to 5,6-dihydrouracil (DHU) using an amine-borane attached to a solid support. The method may include detecting the 5-methylcytosine or 5-hydroxymethylcytosine using the DHU.
An example of a flow cell includes a substrate; a plurality of reactive regions spatially separated from one another across the substrate; and a plurality of independently removable coatings respectively positioned over each of the plurality of reactive regions. Each of the plurality of reactive regions includes a polymeric hydrogel layer; and a reactive entity attached to the polymeric hydrogel layer.
Examples of flow cells include substrates. Embodiments of the present disclosure also relate to methods of fabricating flow cell substrates. Some example workflows exploit light blocking properties of an imprint layer such that the process does not include etch steps. Such processes may be used to create substrates compatible with simultaneous paired-end sequencing methods.
G03F 7/00 - Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printed surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
47.
MONOCLONAL CLUSTERING USING DOUBLE STRANDED DNA SIZE EXCLUSION WITH PATTERNED SEEDING
Embodiments of the present disclosure relate to nucleotide and nucleoside molecules with 3´ vinyl or isonitrile containing blocking groups and/or tetrazine or strained unsaturated ring containing cleavable linkers. Additionally, the present disclosure provides methods of using the nucleoside/nucleotide in oligonucleotide synthesis, and methods of sequencing using the nucleotide described herein.
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
An example flow cell includes a substrate including depressions separated by interstitial regions; a polymeric hydrogel positioned within each of the depressions; a primer set attached to the polymeric hydrogel; and one of: a passivation component attached to the interstitial regions, or a passivation component attached to the polymeric hydrogel, or respective passivation components attached to each of the interstitial regions and the polymeric hydrogel.
Described herein are various methods of removing uracils due to the deamination of unmethylated cytosines in an assay using engineered cytosine deaminases to deaminate methylated cytosines. The Chemoenzymatic Uracil Replacement of Nucleobases (ChURN) method includes providing a sample comprising single stranded DNA library fragments in which a cytosine deaminase has deaminated methylated cytosines; contacting the sample with an uracil DNA glycosylase (UDG) to deglycosylate uracil residues to form abasic sites having a hemiacetal formation within the single stranded DNA library fragments; contacting the sample with a reactive cytosine nucleobase analog to install a cytosine at abasic sites thru a noncanonical linkage; and subjecting the sample to polymerase chain reaction (PCR) amplification resulting in double stranded DNA corrected library fragments. The Uracil Enzymatic Removal and Substitution at Errors (U-ERASE) method includes providing a sample comprising single stranded DNA library fragments in which a cytosine deaminase has deaminated methylated cytosines, synthesizing double stranded DNA library fragments in which the second strand is tagged to facilitate its downstream degradation, treating the double stranded DNA library fragments with an uracil DNA glycosylase and an endonuclease resulting in the removal of uracil bases and single nucleotide gaps at those sites, and repairing the single nucleotide gaps through treatment with a polymerase, dCTP, and a ligase, resulting in replacement of false positive uracil bases with a mismatched base, such as cytosine. Subsequently, the second strand is selectively degraded, allowing for selective amplification of the original DNA strand via PCR.
In an example method, a positive photoresist is deposited over a substrate that includes depressions separated by interstitial regions. The positive photoresist is exposed to ultraviolet light at an angle that is non-perpendicular, non-parallel, and offset from a surface plane of the depressions such that a first portion of the positive photoresist in each depression remains soluble and a second portion of the positive photoresist in each depression is rendered insoluble. The soluble portions of the positive photoresist are removed, which exposes a first substrate portion in each depression. A first functionalized layer is deposited over the first substrate portion in each depression. The insoluble portions of the positive photoresist are removed, which exposes a second substrate portion in each depression. The second functionalized layer is selectively deposited over the second substrate portion in each depression.
This disclosure describes methods, non-transitory computer readable media, and systems that can utilize methylation sequencing assay data to generate genotype calls efficiently and accurately for a target genomic sample. In some implementations, the disclosed system identifies the target genomic sample's nucleotide reads comprising nucleobases converted by a methylation sequencing assay. The disclosed system can determine variant calls based on aligning the nucleotide reads with a reference genome. To account for errors introduced by the methylation sequencing assay, in some cases, the disclosed system corrects or modifies genotype-likelihood metrics for a subset of candidate variant calls. The disclosed system further imputes genotype calls based on such modified genotype-likelihood metrics and a comparison of a subset of variant calls with marker variants from a reference panel.
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
Some examples herein provide a hydrogel on a substrate. The hydrogel includes a three-dimensional network of polymer chains; first functional groups coupled to the polymer chains; amplification primers coupled to the polymer chains via the first functional groups; and second functional groups coupled to the polymer chains and reversibly cross-linking the polymer chains to one another. Some examples herein provide a method of using a hydrogel. The method includes hybridizing a target polynucleotide to an amplification primer coupled to a hydrogel; cleaving cross-linkages within the hydrogel within which the target polynucleotide is hybridized to the amplification primer; and amplifying the target polynucleotide using additional amplification primers within the hydrogel within which the cross-linkages have been cleaved.
A method of determining at least a partial order of fragments derived from a same target template nucleic acid molecule is provided, the method including: a) providing a sample including a target template nucleic acid molecule; b) creating tagged fragments of the target template nucleic acid molecule using sets of tag nucleic acid molecules; c) sequencing at least a portion of the tagged fragments, wherein said portion includes a tag nucleic acid sequence; d) identifying sequences of the tagged fragments that include two or more of the tag nucleic acid sequences that are same, and identifying sequences of the tagged fragments that include two or more of the tag nucleic acid sequences that are different; and e) identifying sequences of the tagged fragments to determine the partial order of the tagged fragments with the target template nucleic acid molecule.
Embodiments herein relate to combinations for use in light energy excitation. Light energy, according to one example, can be directed toward a detector surface that can support biological or chemical samples.
Genome-wide association studies may allow for detection of variants that are statistically significantly associated with disease risk. However, inferring which are the genes underlying these variant associations may be difficult. The presently disclosed approaches utilize machine learning techniques to predict genes from genome-wide association study summary statistics that substantially improves causal gene identification in terms of both precision and recall compared to other techniques.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
57.
DETECTING AND CORRECTING METHYLATION VALUES FROM METHYLATION SEQUENCING ASSAYS
This disclosure describes methods, non-transitory computer readable media, and systems that can use a computationally efficient model to determine a corrected methylation-level value for a specific sample nucleotide sequence. For instance, the disclosed systems determine a false positive rate and a false negative rate at which a given methylation sequencing assay converts cytosine bases. Based on the determined false positive rate and false negative rate, the disclosed systems determine a corrected methylation-level value that corrects for a bias of the given methylation sequencing assay.
322H end group for dual functionality and/or pH responsiveness. For nucleic acid sequencing, amplification primers are grafted to photochemically-reversible hydrogels or nanogel particles reversibly bound to surfaces within a flow cell. After sequencing is complete, the photochemically-reversible hydrogel or nanogel particles is/are removable from the flow cell surfaces by irradiation, enabling the flow cell to be reusable.
Described herein are compositions and methods for enriching library fragments comprising viral sequences prepared from a variety of samples. These methods may incorporate microfluidics and flowcells for greater ease of use. Libraries enriched with the present methods may be used for sequencing. Also described are probes and methods for enzymatic depletion of unwanted RNA.
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
61.
INTEGRATING VARIANT CALLS FROM MULTIPLE SEQUENCING PIPELINES UTILIZING A MACHINE LEARNING ARCHITECTURE
This disclosure describes methods, non-transitory computer readable media, and systems that can generate genotype calls from a combined pipeline for processing nucleotide reads from multiple read types/sources for robust, accurate genotype calls. For example, the disclosed systems can train and/or utilize a genotype-call-integration machine-learning model to generate predictions for genotype calls based on data associated with a first type of nucleotide reads (e.g., short reads) and a second type of nucleotide reads (e.g., long reads). As disclosed, the disclosed systems can determine sequencing metrics and can utilize a genotype-call-integration machine-learning model to generate predictions (e.g., genotype probabilities, variant call classifications) for generating output genotype calls based on the sequencing metrics. The disclosed system can utilize multiple such genotype-call-integration machine-learning models to generate genotype calls for different variant types, such as SNPs and indels, where the genotype-call-integration machine-learning models generate different predictions for each variant type.
Described herein are methods for depleting library fragments prepared from off-target RNA sequences. Libraries enriched or depleted with the present methods may be used for sequencing. Also described are probes and methods for depletion or supplementing depletion of off-target RNA from human and non-human samples.
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
63.
PROBES FOR IMPROVING CORONAVIRUS SAMPLE SURVEILLANCE
Described herein are compositions and methods for enriching library fragments prepared for coronavirus sequences prepared from various samples. These methods may incorporate microfluidics and flowcells for greater ease of use. Libraries enriched with the present methods may be used for sequencing. Also described are probes and methods for enzymatic depletion of unwanted RNA.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
Sequencing systems and methods are provided that include a nanopore well (320) that includes a cis well associated with a cis electrode and a trans well associated with a trans electrode, a membrane separating the cis well and the trans well, and a nanopore well embedded in the membrane providing a channel through the membrane; a command node (312) connected directly to the nanopore well. The command node is configured to apply a potential across the nanopore well and a command pulse. The system further includes an amplifier (340) with a feedback loop (342) coupled to the nanopore well and a switch (366) disposed between the amplifier and the nanopore well. The switch is driven by a clock (362) pulse and configured to ground an inverting input of the amplifier.
Some implementations of the disclosure relate to an imaging system including one or more image sensors and a Z-stage. The imaging system is configured to perform operations including: capturing, using the one or more image sensors, a first image of a first pair of spots projected at a first sample location of a sample; determining whether or not the first image of the first pair of spots is valid; and when the first image is determined to be valid: obtaining, based on the first image, a current separation distance measurement of the first pair of spots; and controlling, based at least on the current separation distance measurement, the Z-stage to focus the imaging system at the first sample location.
Provided herein are methods, compositions, and kits related to using a CpG binding protein. In one embodiment, the present disclosure includes methods, compositions, and kits related to using a CpG binding protein with a cytidine deaminase protein to identify methylated cytosine nucleotides. The cytidine deaminase can be an altered cytidine deaminase that includes an amino acid substitution mutation at a position functionally equivalent to (Tyr/Phe)130 in a wild-type APOBEC3A protein. In another embodiment, the present disclosure includes methods, compositions, and kits related to using a CpG binding protein with a ten-eleven translocase (TET) protein to identify methylated cytosine nucleotides.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C12N 9/78 - Hydrolases (3.) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
C12N 15/52 - Genes encoding for enzymes or proenzymes
C12N 15/62 - DNA sequences coding for fusion proteins
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
This disclosure describes methods, non-transitory computer readable media, and systems that can utilize a machine-learning model to refine structural variant calls of a call generation model. For example, the disclosed systems can train and utilize a structural variant refinement machine-learning model to reduce false positives and/or false negatives. Indeed, the disclosed systems can improve or refine structural variant calls (e.g., between 50-200 base pairs in length) determined by a call generation model by training and utilizing the structural variant refinement machine-learning model. As disclosed, the systems can determine sequencing metrics and can customize training data for a structural variant refinement machine-learning model to generate modified structural variant calls.
A method of processing sequence data comprising a known location of the start of a copy number variant breakpoint to generate a prediction for the location of the end of the copy number variant breakpoint. The method comprises an encoder and a copy number variation (CNV) caller guide. The encoder processes an anchor sequence and corresponding subject candidate sequence to generate a learned representation of the anchor sequence and a learned representation of the corresponding subject candidate sequence. The CNV caller guide determines a similarity between the learned representation of the anchor sequence and a learned representation of the corresponding subject candidate sequence. Similarity between anchor sequence and subject candidate sequence is used as a proxy for likelihood that the end of the CNV breakpoint is located on the subject candidate sequence.
An example of a flow cell includes a substrate and a reaction area defined in or over the substrate. The reaction area includes two angularly offset and non-perpendicular surfaces relative to a planar surface of the substrate, a polymeric hydrogel positioned over at least a portion of each of the two angularly offset and non-perpendicular surfaces; a first primer set attached to the polymeric hydrogel that is positioned over the portion of a first of the two angularly offset and non-perpendicular surfaces; and a second primer set attached to the polymeric hydrogel that is positioned over the portion of a second of the two angularly offset and non-perpendicular surfaces, wherein the first and second primer sets are orthogonal.
Embodiments of the present disclosure relate to cyclooctatetraene containing dyes and their uses as fluorescent labels. Also provided are composition containing cyclooctatetraene. The dyes and compositions may be used in various biological applications, such as nucleic acid sequencing.
Presented herein are altered polymerase enzymes for improved incorporation of nucleotides and nucleotide analogues, in particular altered polymerases that maintain low error rate, low phasing rate, or increased incorporation rate for a second generation ffN under reduced incorporation times, as well as methods and kits using the same.
Protein complexes including a cytidine deaminase and a helicase. In some embodiments, the cytidine deaminase is an altered cytidine deaminase. In some embodiments, the protein complex converts 5 methylcytosine to thymine. Kits, compositions, and methods of use for the protein complexes including a cytidine deaminase and a helicase are also described.
The presently described techniques relate generally to providing motion feedback (e.g., motion system calibration and/or sample alignment) in the context of an imaging system (such as a time delay and integration (TDI) based imaging system). The architecture and techniques discussed may achieve nanoscale control and calibration of a movement feedback system without a high-resolution encoder subsystem or, in the alternative embodiments, with a lower resolution (and correspondingly less expensive) encoder subsystem than might otherwise be employed. By way of example, certain embodiments described herein relate to ascertaining or calibrating linear motion of a sample holder surface using nanoscale features (e.g., sample sites or nanowells or lithographically patterned features) provided on a surface of the sample holder.
ffff) seconds after the start of the initial acceleration segment. The acceleration intervals may be defined by a start time, an amplitude profile, and/or a time duration. In some implementations, the amplitude and time duration of each acceleration pulse may be different. The amplitude and time duration of acceleration steps may be determined and adjusted to compensate for the particular resonance frequency of an individual system, and programmed into a controller for the stage using motor programming controls.
An apparatus includes a flow cell, an imaging assembly, and a processor. The flow cell includes a channel and a plurality of reaction sites. The imaging assembly is operable to receive light emitted from the reaction sites in response to an excitation light. The processor is configured to drive relative movement between at least a portion of the imaging assembly and the flow cell along a continuous range of motion to thereby enable the imaging assembly to capture images along the length of the channel. The processor is also configured to activate the imaging assembly to capture one or more calibration images of one or more calibration regions of the channel, during a first portion of the continuous range of motion. The processor is also configured to activate the imaging assembly to capture images of the reaction sites during a second portion of the continuous range of motion.
G01N 21/27 - Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection
Liquid reservoirs, cartridge assemblies and related systems and methods are disclosed. An example implementation includes an apparatus that includes a body, a cover, and a lid assembly. The body includes a top surface and a storage chamber having an opening at the top surface. The cover covers or is positioned within the opening of the storage chamber. The lid assembly is coupled to the top surface and covers the opening of the storage chamber. The top surface and the first portion define a plenum. The cover is at least one of piercable, breakable, or movable to allow the storage chamber to be fluidly coupled to the plenum without venting the plenum to atmosphere.
The present disclosure is concerned with proteins, methods, compositions, and kits for mapping of methylation status of nucleic acids. In one embodiment, proteins are provided that selectively act on certain modified cytosines of target nucleic acids and converts them to thymine. Also provided are compositions and kits that include one or more of the proteins and methods for using one or more of the proteins.
Disclosed herein are methods and systems for determining a score for the copy number of repeat units in a variable number tandem repeat (VNTR) locus in a target polynucleotide. Also disclosed herein are methods and systems for determining the nucleotide sequence of a sample nucleic acid having repeat units, where the methods and systems may utilize the most likely copy number of repeat units determined according to the aforementioned methods and systems. Also disclosed herein are methods and systems for predicting a feature of a subject, wherein the methods and systems may utilize the score for the copy number of repeat units in a VNTR locus in a target polynucleotide determined according to the aforementioned methods and systems.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
80.
NUCLEIC ACID SEQUENCING COMPONENTS INCLUDING A GLYCOLIPID BI-LAYER
An example of a nucleic acid sequencing component includes a support. A glycolipid bi-layer is attached to at least a portion of the support. First and second primers are respectively attached to the glycolipid bi-layer. In one example, the support is a substrate of a flow cell. In another example, the support is a core nanostructure that can be introduced into a flow cell.
The present disclosure relates to systems, non-transitory computer-readable media, and methods for generating a target-variant-reference panel comprising a target-variant position with target-variant indicators or using the target-variant-reference panel to impute a genotype call for the corresponding target variant. In particular, in one or more embodiments, the disclosed systems generate an initial reference panel including a variety of phased genomic samples of different haplotypes. The disclosed systems further add a target-variant position to the initial reference panel to indicate a presence or absence of a target variant, thereby creating a target-variant-reference panel comprising a target-variant position with target-variant indicators. Additionally or alternatively, the disclosed systems can utilize the target-variant-reference panel to impute genotype calls indicating a presence or absence of a target variant within a target genomic sample based on a comparison of (i) haplotypes represented in the target-variant-reference panel and (ii) nucleotide reads corresponding to the target genomic sample.
This disclosure relates to novel thermophilic amplification compositions and methods, in particular for use in nucleic acid amplification and sequencing.
This disclosure relates to novel amplification compositions and methods, in particular for use in nucleic acid amplification and sequencing, preferably that do not involve reagents that are thermophilic.
In some examples, novel nanogel particles are described having dual functionality, temperature responsiveness and pH responsiveness. For nucleic acid sequencing, amplification primers are grafted to nanogel particles to form primer-grafted nanogel particles, and the primer-grafted nanogel particles are captured onto surfaces within a flow cell. Within flow cells such as used in SBS nucleic acid sequencing, each primer-grafted nanogel particle functions as a nano-well in the flow cell, thus eliminating the need for nano-wells in some examples.
Versions of a sequencing system may be monitored to enable changing of a version of a server subsystem operating the sequencing system to service requests from client subsystems for performing analysis of sequencing data. A monitor subsystem may be utilized for receiving and authorizing requests from client subsystems. The monitor subsystem may identify a version associated with a server subsystem operating the sequencing system to be implemented for servicing the request. The monitor subsystem may allow the server subsystem to be accessed for servicing the request from the client subsystem when the version associated with the client subsystem is compatible with the version associated with the server subsystem. The monitor subsystem may prevent the server subsystem from being accessed when the version associated with the client subsystem is incompatible with the version associated with the server subsystem.
G16B 50/00 - ICT programming tools or database systems specially adapted for bioinformatics
G16B 50/30 - Data warehousing; Computing architectures
G06F 21/57 - Certifying or maintaining trusted computer platforms, e.g. secure boots or power-downs, version controls, system software checks, secure updates or assessing vulnerabilities
G06F 8/71 - Version control ; Configuration management
G06F 21/62 - Protecting access to data via a platform, e.g. using keys or access control rules
The invention relates to deformable polymers comprising immobilised primers, particularly for use in nucleic acid sequencing, such as concurrent sequencing.
Systems, methods, and apparatus are described herein for performing sequencing of one or more biological samples in at least two flow cells on a sequencing device. A sequencing system may comprise one or more of a scheduling engine, the sequencing device, and a display. The scheduling engine may maintain scheduling information of a state of compute resources and non-compute resources. The sequencing device may receive the scheduling information from the scheduling engine; determine the state of the compute resources and non-compute resources; determine a sequencing analysis priority associated with performing analysis of the at least two flow cells on the sequencing device; and perform the sequencing task related to the one or more biological samples in the at least two flow cells according to the sequencing analysis priority. The display may display real-time feedback associated with completion of the sequencing task for each flow cell.
The technology disclosed is directed to cluster segmentation and base calling. The technology disclosed describes a computer-implemented method including segmenting a population of clusters into a plurality of subpopulations of clusters based on one or more prior bases called at one or more prior sequencing cycles of a sequencing run. At a current sequencing cycle of the sequencing run, the method includes applying a mixture of four distributions to current sequenced data of each subpopulation of clusters in the plurality of subpopulations of clusters, the four distributions corresponding to four bases adenine (A), cytosine (C), guanine (G), and thymine (T), and the current sequenced data being generated at the current sequencing cycle. The method further includes base calling clusters in a particular subpopulation of clusters using a corresponding mixture of four distributions.
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
91.
REUSABLE FLOW CELLS HAVING SIGNAL INTENSITY RETENTION, METHODS OF RETAINING SIGNAL INTENSITY IN REUSABLE FLOW CELLS AND REAGENTS AND KITS THEREFOR
Reusable flow cells for sequencing which exhibit signal intensity retention over numerous use cycles, the active surface of which contains poly-azide functional moieties, methods of treating flow cells surfaces with reagents to provide such poly-azide functional moieties, and reagents therefor.
Some embodiments of the methods and compositions provided herein relate to blocked substrates in which non-specific binding of nucleic acids to the substrate is reduced. Some embodiments include use of carrier nucleic acids. More embodiments include the use of beads contacted with an oligonucleotide, such as an oligonucleotide containing one or more phosphorothioate bonds. Such substrates are useful in methods for obtaining long-read information from short reads of a target nucleic acid.
An example flow cell includes a patterned substrate having an active region and a bonding region that at least partially surrounds the active region. The active region includes first depressions defined in a layer of the patterned substrate, surface chemistry positioned in the first depressions, and first interstitial regions surrounding the first depressions. The bonding region includes second depressions defined in the layer and second interstitial regions surrounding the second depressions. An adhesive is positioned over the second depressions and over the second interstitial regions. A cover is attached to the adhesive such that a flow channel is defined between a portion of the cover and the active region.
B01J 19/00 - Chemical, physical or physico-chemical processes in general; Their relevant apparatus
94.
METHODS OF MODIFYING METHYLCYTOSINE OR DERIVATIVE THEREOF USING A NUCLEOPHILIC MOLECULE, AND METHODS OF USING THE SAME TO DETECT THE METHYLCYTOSINE OR DERIVATIVE THEREOF IN A POLYNUCLEOTIDE
Disclosed herein are methods of modifying 5-methylcytosine (5-mC), 5- hydroxymethylcytosine (5-hmC), or 5-formlcytosine (5-fC) in a polynucleotide. The method may include oxidizing the 5-mC, 5-hmC, or 5-fC to 5-carboxylcytosine (5-caC); activating the 5-carboxyl group of the 5-caC; and reacting the activated 5-carboxyl group with a nucleophilic molecule to form a product. In some examples, the product may be used to detect the 5-mC, 5-hmC, or 5-fC in the polynucleotide.
Embodiments of the present disclosure relate to six-nucleobase libraries having a third Watson-Crick base pair. Also provided herein are methods to prepare such six-nucleobase libraries, and their use for sequencing and modified nucleobase detection applications.
The technology disclosed relates to reliably identifying variants that cause extreme levels of gene expression. Extreme levels of gene expression include under expression and over expression. Then, these variants may be used to train artificial intelligence based models for a variety of prediction tasks. One example of the prediction tasks is to produce per-base resolution for chromatin sequences. Another example of the chromatin task is to produce gene expression changes caused by the reliably identified variants.
Non-contact dispensers and related systems and methods are disclosed. In accordance with an implementation, an apparatus includes a pump having a body that defines an inlet, an outlet, and a flow path fluidly coupling the inlet and the outlet. A first displacement member is movable from a first position to a second position within the flow path to urge a first volume of the fluid out of the outlet. A second displacement member is movable from a first position to a second position within the flow path to urge a second volume of the fluid out of the outlet.
The technology disclosed relates to detecting gene conservation and expression preservation. In particular, the technology disclosed relates to detecting gene conservation and epigenetic signals for a reference genetic sequence (302) in comparison to a variant of the reference genetic sequence (302) at base resolution through the generation of a plurality of alternative representations (300) of the sequence in chromatin form which may represent evolutionary conservation, transcription initiation, or epigenetic signals, mapping the plurality of alternative chromatin sequences to a gene expression alterability classifier (2700) to generate a gene expression class prediction for the variant, and mapping the alternative chromatin sequence to a pathogenicity predictor to detect pathogenicity of variants.
This disclosure describes methods, non-transitory-computer readable media, and systems that can use a single executable file to run a single-cell multiomics analysis that (i) aligns multiomics reads with a reference genome and (ii) jointly filters cellular barcode sequences for cells based on feature-specific, single-cell read counts. To run such an assay, the disclosed systems identify transcriptomic reads and genomic reads for a sample, where such reads comprise different sets of cellular barcode sequences. In some cases, the disclosed systems further use separate invocations of a configurable processor to align the transcriptomic reads and genomics reads with a reference genome. Based on single-cell counts of aligned transcriptomic reads and aligned genomic reads for target nucleotide sequences, the disclosed systems select a subset of candidate cells corresponding to a subset of cellular barcode sequences. The disclosed systems further generate, for the sample, single-cell multiomics outputs based on the counts of aligned reads.
The presently described techniques relate generally to providing motion feedback (e.g., motion system calibration and/or sample alignment) in the context of an imaging system (such as a time delay and integration (TDI) based imaging system). The architecture and techniques discussed may achieve nanoscale control and calibration of a movement feedback system without a high-resolution encoder subsystem or, in the alternative embodiments, with a lower resolution (and correspondingly less expensive) encoder subsystem than might otherwise be employed. By way of example, certain embodiments described herein relate to ascertaining or calibrating linear motion of a sample holder surface using nanoscale features (e.g., sample sites or nanowells or lithographically patterned features) provided on a surface of the sample holder.
patents
