The Voltage-Gated Calcium Channel auxiliary subunit α2δ-1 is the target/receptor of gabapentinoid compounds known to exert therapeutic effects as for example in Epilepsy and Neuropathic pain. Gabapentinoids are known to exert their action via binding Arginine (R) within an RRR motif located at the N-terminal of the α2δ-1. The present invention describes a novel binding site for gabapentinoids which is located within the VGCC_a2 domain and within an IKAK aminoacid sequence of the α2δ-1. Such newly identified amino acid binding site finds utility in the identification and characterization of novel compounds with therapeutic properties in Neuropathic Pain and in other disorders and conditions in which α2δ-1 is involved in.

The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.

The present invention relates to a polypeptide comprising an antigen binding domain and a carrying moiety having an inhibiting domain that inhibits the antigen binding activity of the antigen binding domain, and having a longer half-life than that of the antigen binding domain existing alone, methods for producing and screening for the polypeptide, a pharmaceutical composition comprising the polypeptide, methods for producing and screening for a single-domain antibody whose antigen binding activity is inhibited by associating with particular VL, VH or VHH, and a fusion polypeptide library including a single-domain antibody whose antigen binding activity is inhibited by associating with particular VL, VH or VHH.

Methods for proteomic screening on random protein-bead arrays by mass spec is described. Photocleavable mass tags are utilized to code a protein library (bait molecules) displayed on beads randomly arrayed in an array substrate. A library of probes (prey) can be mixed with the protein-bead array to query the array. Because mass spec can detect multiple mass tags, it is possible to rapidly identify all of the interactions resulting from this mixing.

A processing platform in one embodiment comprises one or more processing devices each including at least one processor coupled to a memory. The processing platform is configured to implement a crosslink identification and validation algorithm for processing multiple levels of mass spectrometry data in order to identify and validate protein-protein interactions within the mass spectrometry data. In conjunction with execution of the crosslink identification and validation algorithm, the processing platform is further configured to obtain mass spectrometry spectra for each of the multiple levels, to apply a header matching filter to identify at least one potential crosslink relating one or more first level spectra and one or more second level spectra utilizing a plurality of third level spectra, and to apply one or more mass validation filters to identify whether or not the potential crosslink is a valid crosslink.

The present invention relates to a cell comprising a first nucleic acid sequence encoding a first polypeptide fused to the N-terminus of a first variant of a histidine kinase comprising a DHp domain and a CA domain, wherein said first variant does not comprise a transmembrane domain, a second nucleic acid sequence encoding a second polypeptide fused to the N-terminus of a second variant of said histidine kinase comprising a DHp domain and a CA domain, wherein said second variant does not comprise a transmembrane domain, and a third nucleic acid sequence encoding a response regulatory protein specifically phosphorylatable by said DHp domain of said first or said second variant. The present invention further relates to uses of the cell of the invention.

Methods for proteomic screening on random protein-bead arrays by mass spec is described. Photocleavable mass tags are utilized to code a protein library (bait molecules) displayed on beads randomly arrayed in an array substrate. A library of probes (prey) can be mixed with the protein-bead array to query the array. Because mass spec can detect multiple mass tags, it is possible to rapidly identify all of the interactions resulting from this mixing.

The present invention relates to a two-part device, wherein a first part is an engineered antigen-presenting cell system (eAPCS), and a second part is an engineered TCR-presenting cell system (eTPCS).

The disclosure features methods of identifying protein-protein deregulation that include: generating a basal protein-protein interaction network for a plurality of biological samples, the network featuring a set of proteins expressed in the biological samples and concentrations of each member of the set of expressed proteins in each of the biological samples; identifying two associated expressed proteins in the network; for the two associated expressed proteins, comparing correlated relative concentration values of the two proteins in each of the biological samples to identify outliers among a distribution of the relative concentration values; and identifying members of the plurality of biological samples in which deregulation of the two associated expressed proteins occurs based on the outliers.

The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.