The present disclosure provides methods of processing or analyzing a sample. A method for processing a sample may comprise hybridizing a probe molecule to a target region of a nucleic acid molecule (e.g., a ribonucleic acid (RNA) molecule), barcoding the probe-nucleic acid molecule complex, and performing extension, denaturation, and amplification processes. A method for processing a sample may comprise hybridizing first and second probes to adjacent or non-adjacent target regions of a nucleic acid molecule (e.g., an RNA molecule), linking the first and second probes to provide a probe-linked nucleic acid molecule, and barcoding the probe-linked nucleic acid molecule. One or more processes of the methods described herein may be performed within a partition, such as a droplet or well. One or more processes of the methods described herein may be performed on a cell, such as a permeabilized cell.

Embodiments of the present disclosure pertain to methods of selecting cyclic peptides that bind to a target by transforming a phage display library with a plurality of nucleic acids into bacterial host cells, where the nucleic acids include phage coat protein genes with a combinatorial region that encodes at least one cysteine and at least one non-canonical amino acid. The transformation results in the production of phage particles with phage coat proteins where the cysteine and the non-canonical amino acid couple to one another to form a cyclic peptide library. Phage particles are then screened against the desired target to select bound cyclic peptides. Amino acid sequences of the selected cyclic peptides are then identified. Additional embodiments pertain to methods of constructing a phage display library that encodes the cyclic peptides. Further embodiments of the present disclosure pertain to the produced cyclic peptides, phage display libraries and phage particles.

The invention provides a method of measuring the affinity of first and second biomolecules in which a first biomolecule is tethered by a first tether portion having a first tether portion length and a second biomolecule is tethered by a second tether portion having a second tether portion length, the method comprising determining binding of adjacent first and second biomolecules to each other, varying at least one of the first and second tether lengths and determining binding of the first and second biomolecules. The invention also provides apparatus suitable for use in the method of the invention.

The present invention provides a vector library for yeast two-hybrid screening of a deubiquitinating enzyme that binds to a target protein and a method for identifying a deubiquitinating enzyme binding to a target protein using the same. Also, the present invention provides a method for screening an agent having anti-cancer activity targeting the deubiquitinating enzyme USP1, USP7, USP12, or USP49 identified by said identifying method.

Compounds, composition, and kits are provided for use in methods for the assisted folding of protein fragments of a of choice point larger protein by means of induced proximity, forced by specific nucleic acid hybridizations between a target nucleic acid molecule and complementary nucleic acid molecules appended to the protein fragments of interest.

Methods for display of recombinant proteins or protein libraries on the surface of lower eukaryotes such as yeast and filamentous fungi are described. The methods are useful for screening libraries of recombinant proteins in lower eukaryotes to identify particular proteins with desired properties from the array of proteins in the libraries. The methods are particularly useful for constructing and screening antibody libraries in lower eukaryotes.

Provided is an anti-CRISPR protein (AcrVIA1), which acts as an inhibitor of the nuclease of Cas13. Cas13 recognizes complementary viral transcripts to trigger the degradation of both host and viral RNA during the type VI CRISPR-Cas antiviral response. AcrVIA1 is provided as an isolated or recombinantly expressed protein comprising the sequence of SEQ ID NO:1, or derivatives thereof, expression vectors that encode the same sequence, and methods of making and using proteins that comprise the same sequence, or derivatives thereof, for inhibiting the function of Cas13 and/or protein complexes and/or ribonucleoprotein complexes that comprise Cas13. The disclosure further includes use of the described inhibitor protein in improved diagnostic assays that include Cas13. Inclusion of the inhibitor is expected to preclude a requirement to reverse transcribe and/or create cDNA amplifications of the particular RNA that is the subject of the analysis.

Provided herein are methods for identifying pairs of protein binding partners, mutations of which may inform the discovery of pharmaceutically useful small molecules. The methods disclosed herein may allow for the adaptation of the native protein degradation system to modulate specific disease targets at the protein level, in particular, for targets that have long been considered undruggable.

The present invention relates to methods and means for implementing evolution of a gene of interest inside bacterial cells.

The disclosure provides methods for determining the presence of coronavirus neutralizing antibodies in a sample as well as associated compositions and kits. The methods of the disclosure use recombinant vesicular stomatitis virus (VSV) particles, wherein the VSV glycoprotein (G) is replaced by a coronavirus spike (S) glycoprotein or a fragment or a derivative thereof. In a specific embodiment, the S glycoprotein is derived from Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) and the methods are used for determining the presence of SARS-CoV-2 neutralizing antibodies.