Provided herein are methods of identifying a location of an RNA in a sample that include: (a) contacting the sample with an array comprising capture probes, where a capture probe comprises a capture domain and a spatial barcode; (b) releasing the RNA from the sample; (c) extending a 3 end of the capture probe using the capture domain-bound RNA as a template; (d) generating nick(s) in the extended capture probe-hybridized RNA and performing random-primed DNA synthesis; (e) performing end repair on the second strand DNA molecule; (f) adding a single adenosine nucleotide to the 3 end of the extended capture probe; (g) ligating a double-stranded sequencing adaptor to the double-stranded DNA product; and (h) determining all or a part of the sequence of the RNA, and the sequence of the spatial barcode, or complements thereof, and using the determined sequences to identify the location of the RNA in the sample.

In some embodiments, the disclosure relates generally to methods as well as related compositions, systems, kits and apparatus comprising linking proteins to target compounds and/or to locations of interest using tethers. For example, the tether can be used to link the protein to a target compound, for example, to link an enzyme to a substrate. Similarly, the tether can be used to link the protein at or near a desired location on a surface. In one group of embodiments, the tether includes a polynucleotide and the target compound or location on the surface includes another polynucleotide that is capable of hybridizing to the tether. In such embodiments, the tether can be used to link the protein to the target compound or location using nucleic acid hybridization.

Methods and compounds are disclosed for irreversibly inhibiting a DNA polymerase, including DNA polymerase (pol ). Also disclosed are methods for inducing a synthetic lethality in a breast cancer type 1 (BRCA1)-deficient cancer cell, the method comprising inhibiting DNA polymerase by administering a presently disclosed pol inhibitor.

The invention provides a novel class of cyanine dyes that are functionalized with a linker moiety that facilitates their conjugation to other species and substituent groups which increase the water-solubility, and optimize the optical properties of the dyes. Also provided are conjugates of the dyes, methods of using the dyes and their conjugates and kits including the dyes and their conjugates.

The invention provides methods and compositions for detecting a change in a nucleic acid polymerase conformation involving contacting a nucleic acid polymerase non-covalently attached to a single walled carbon nanotube (SWNT) with a first nucleotide or first nucleotide analog and a template and detecting the conformationally changed nucleic acid polymerase by measuring a first electrical conductance change in the SWNT between the nucleic acid polymerase and the conformationally changed nucleic acid polymerase. The method is useful for sequencing of polynucleotides.

In some embodiments, the disclosure relates generally to methods as well as related compositions, systems, kits and apparatus comprising linking proteins to target compounds and/or to locations of interest using tethers. For example, the tether can be used to link the protein to a target compound, for example, to link an enzyme to a substrate. Similarly, the tether can be used to link the protein at or near a desired location on a surface. In one group of embodiments, the tether includes a polynucleotide and the target compound or location on the surface includes another polynucleotide that is capable of hybridizing to the tether. In such embodiments, the tether can be used to link the protein to the target compound or location using nucleic acid hybridization.

The present invention provides compounds and methods of use thereof for assessing target engagement for DNA polymerase theta. In particular, provided herein are tracer compounds comprising a small molecule that binds DNA polymerase theta tethered to a fluorophore, and methods of use thereof in target engagement assays.

The present disclosure provides systems and methods directed towards single molecule protein sequencing, through use of a barcode transfer reagent. Systems and methods described herein allow for massively parallel single-molecule protein sequencing through molecular barcoding and ex-situ analysis.

Methods for rapidly and accurately detecting genetic material from hop latent viroid RNA (HLVd) that combines reverse transcription loop-mediated isothermal amplification (RT-LAMP) technology with specific oligonucleotide primers, fluorophore-labeled oligonucleotide primers, quencher-conjugated oligonucleotide primers, pH buffers, and enzymes, are described. The methods include at least one internal positive control targeting sequence, for minimizing false positive and false negative results, thereby allowing more certain interpretation of the results. The reaction can be performed at a single elevated temperature, can be completed in 1-1.5 hours, and the results can readily be interpreted by visually observing the fluorescence color of the reaction using ultraviolet light, or by using an electronic image acquisition system for viewing fluorescence results from one or more reactions.

Provided is a kit for calibration of an isothermal polymerase chain reaction (PCR) analyzer and use thereof. The kit includes a standard substance, an amplification primer set, a reaction buffer, a polymerase, a dye, and a negative control. The standard substance is a DNA plasmid with a gradient concentration of 10.sup.0 copies/L to 10.sup.6 copies/L; the amplification primer set has nucleotide sequences shown in SEQ ID NO: 1 to SEQ ID NO: 6; the polymerase is a Bst DNA polymerase; and the dye is a loop-mediated isothermal amplification (LAMP) fluorescent dye (with excitation: 485 nm, emission: 498 nm, and a detection channel of SYBR Green I or a FAM channel). The kit and a technology for calibration of an isothermal PCR instrument meet calibration demands of the isothermal PCR instrument and fill a technical gap.