The present disclosure is directed methods and products for synthesizing and using targeted templated assembly reactants comprising at least one nucleic acid recognition moiety, at least one selectively-reactive moiety, and at least one effector partial moiety. The nucleic acid recognition moiety can bind a target nucleic acid sequence within a sample. The nucleic acid recognition moiety also can bind the selectively-reactive moiety. Additionally, the effector partial moiety can bind the selectively-reactive moiety to produce an active effector structure. Also disclosed are methods of delivering the targeted templated assembly reactants and active effector structures formed front the targeted templated assembly reactants.

The present disclosure is directed methods and products for synthesizing and using targeted templated assembly reactants comprising at least one nucleic acid recognition moiety, at least one selectively-reactive moiety, and at least one effector partial moiety. The nucleic acid recognition moiety can bind a target nucleic acid sequence within a sample. The nucleic acid recognition moiety also can bind the selectively-reactive moiety. Additionally, the effector partial moiety can bind the selectively-reactive moiety to produce an active effector structure. Also disclosed are methods of delivering the targeted templated assembly reactants and active effector structures formed front the targeted templated assembly reactants.

Novel engineered compositions, reagents, and methods are described that facilitate NGS analysis of both random and specific nucleic acid sequences in a sample by providing high efficiency target enrichment and improved error suppression. Specifically, the design and use of engineered NGS dual adapter molecules with homology regions (HRs) targeted at the 5 and 3 regions of a double-stranded DNA target, unique molecule identifiers (UMIs), and NGS adapters allows target libraries to be created for subsequent NGS analysis.

A method of characterizing candidate agents including steps of (a) providing a library of candidate agents attached to nucleic acid tags; (b) contacting the library with a solid support to attach the candidate agents to the solid support, whereby an array of candidate agents is formed; (c) contacting the array with a screening agent, wherein one or more candidate agents in the array react with the screening agent; (d) detecting the array to determine that at least one candidate agent in the array reacts with the screening agent; (e) sequencing the nucleic acid tag to determine the tag sequences attached to candidate agents in the array; and (f) identifying the at least one candidate agent in the array that reacts with the screening agent based on the tag sequence that is attached to the at least one candidate agent.

The present invention relates to oligonucleotide-encoded libraries and methods of tagging such libraries. In particular, the methods and oligonucleotides can include one or more 2-substituted nucleotides, such as 2-O-methyl or 2-fluoro nucleotides, and other conditions or reagents to enhance enzyme ligation or one or more chemical functionalities to support chemical ligation.

Provided are methods of adding adapters to nucleic acids. The methods include combining in a reaction mixture a template ribonucleic acid (RNA), a template switch oligonucleotide including a 3 hybridization domain and a sequencing platform adapter construct, a polymerase, and dNTPs. The reaction mixture components are combined under conditions sufficient to produce a product nucleic acid that includes the template RNA and the template switch oligonucleotide each hybridized to adjacent regions of a single product nucleic acid that includes a region polymerized from the dNTPs by the polymerase. Aspects of the invention further include compositions and kits.

Systems, methods, and machine-readable instructions stored on machine-readable media are disclosed for receiving a first DNA sequencing result and a second DNA sequencing result, wherein the first DNA sequencing result is a result of a first DNA sequencing technique and the second DNA sequencing result is a result of a second DNA sequencing technique. A difference is determined between the first DNA sequencing result and the second DNA sequencing result. Parameters are scored corresponding to the first DNA sequencing result and to the second DNA sequencing result, wherein the scoring includes: determining a value range of a parameter in a set of reference parameters corresponding to a value of a corresponding parameter of the parameters; and assigning a score associated with the value range of the parameter in the set of reference parameters as a score of the corresponding parameter. A determination is made that the first DNA sequencing result or the second DNA sequencing result is conclusive or inconclusive based on respective scores of the parameters of the first DNA sequencing result and the second DNA sequencing result. An indication is made to perform a third DNA sequencing using a third DNA sequencing technique when the first DNA sequencing result or the second DNA sequencing result is inconclusive.

The present invention provides methods, compositions and kits for targeted nucleic acid sequence enrichment in a nucleic acid sample and for high efficiency nucleic acid library generation for next generation sequencing (NGS). Specifically, the methods, compositions and kits provided herein are useful for the production and capture of amplification-ready, target-specific and strand-specific regions of interest from nucleic acid samples containing complex DNA.

Disclosed herein are antigenic peptide-MHC molecules, termed comPACTs, and methods of producing such molecules. Also disclosed herein are methods of producing libraries of comPACT polynucleotides and polypeptides, and their exemplary use in capturing cancer neoepitope-reactive T cells.

The present invention provides nucleic acid templates (e.g., including orthogonal codon sets (e.g., codons from orthogonal codon sets depicted in Tables 5 or 7)) for DNA-templated methods of synthesizing, selecting, and amplifying compounds (e.g., polymers and/or small molecules) described herein. Also provided are novel macrocyclic compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, libraries, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing a disease (e.g., a disease associated with aberrant enzyme activity (e.g., aberrant protease and/or kinase activity (e.g., aberrant IDE activity)), impaired insulin signaling, or insulin resistance in a subject (e.g., a subject having diabetes). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit aberrant protease activity (e.g., aberrant IDE activity).