Patent classifications
G01N33/6842
USE OF DECOY POLYNUCLEOTIDES IN SINGLE CELL MULTIOMICS
Disclosed herein include systems, methods, compositions, and kits for using decoy polynucleotides in noise reduction. Decoy oligonucleotides provided herein can, in some embodiments, prevent or reduce undesirable non-specific binding of intracellular target-binding reagent specific oligonucleotides or protein target-binding reagent specific oligonucleotides to non-target cellular/endogenous nucleic acids, and therefore reduce noise in methods provided herein, such as, for example, single cell multiomics analysis.
Method to map protein landscapes
In shotgun proteomics, generally only a fraction of peptides from a parent protein are actually detected. Because a large portion of the protein sequence is not detected, it is often impossible to determine whether the expressed protein is present in a modified, spliced, or truncated form. Provided herein are methods and systems for analyzing polypeptides which allow for the increase of the mean sequence coverage of a protein concomitant with bioinformatics analysis in order to distinguish putative proteoforms with improved amino acid resolution. Aspects of the invention include (1) a deep sequencing strategy to provide more protein sequence coverage than is typically achieved, and (2) a computational approach to view protein expression across its full length and identify regions of the protein that are potentially subject to such regulation. This technology has global utility in proteomics and will be of particular use for the analysis of biosimilar protein drug therapeutics.
NOVEL PHOTOCLEAVABLE MASS-TAGS FOR MULTIPLEXED MASS SPECTROMETRIC IMAGING OF TISSUES USING BIOMOLECULAR PROBES
The field of this invention relates to immunohistochemistry (IHC) and in situ hybridization (ISH) for the targeted detection and mapping of biomolecules (e.g., proteins and miRNAs) in tissues or cells for example, for research use and for clinical use such by pathologists (e.g., biomarker analyses of a resected tumor or tumor biopsy). In particular, the use of mass spectrometric imaging (MSI) as a mode to detect and map the biomolecules in tissues or cells for example. More specifically, the field of this invention relates to photocleavable mass-tag reagents which are attached to probes such as antibodies and nucleic acids and used to achieve multiplex immunohistochemistry and in situ hybridization, with MSI as the mode of detection/readout. Probe types other than antibodies and nucleic acids are also covered in the field of invention, including but not limited to carbohydrate-binding proteins (e.g., lectins), receptors and ligands. Finally, the field of the invention also encompasses multi-omic MSI procedures, where MSI of photocleavable mass-tag probes is combined with other modes of MSI, such as direct label-free MSI of endogenous biomolecules from the biospecimen (e.g., tissue), whereby said biomolecules can be intact or digested (e.g., chemically digested or by enzyme).
BIOMARKERS, METHODS, AND COMPOSITIONS FOR TREATING AUTOIMMUNE DISEASE INCLUDING SYSTEMIC LUPUS ERYTHEMATOUS (SLE)
The disclosure relates to methods of detecting one or more biomarkers. and/or treating autoimmune diseases such as systemic lupus erythematous (SLE) with an anti-CD19 antibody based on the presence of such biomarkers. The biomarkers can be separate or in combination, and their detection can be used in multiple different methods.
COMPUTER ASSISTED METHOD FOR THE EVALUATION OF CARDIAC METABOLISM
The invention relates to a computation based method for determining an individual cardiac metabolic profile in a subject and related materials, devices and mathematical model usage. The present invention therefore relates to a computation-based method for determining an individual metabolic cardiac profile of a subject comprising provision of a heart tissue sample from said subject, quantifying proteins in said sample from said subject, and applying information about quantities of said proteins to a mathematical model. In some embodiments, individual cardiac parameters and/or the metabolites of the subject are additionally introduced into the mathematical model, wherein individual cardiac parameters are determined for a plurality of cardiac workloads, including rest, stress or cardiac pacing. The invention also relates to the individual cardiac metabolic profile comprising a substrate uptake rate, a myocardial ATP consumption, a myocardial ATP production reserve, a myocardial ATP production at said cardiac workload, and a myocardial ATP production at maximal workload, wherein the myocardial ATP production reserve is calculated as the difference between the myocardial ATP-production at said cardiac workload and the myocardial ATP production at maximal workload. The invention further relates to the medical use and corresponding therapeutic methods based on the individual metabolic cardiac profile of the invention in the treatment, prevention, ascertainment, prognosis, of a medical condition associated with a cardiovascular disorder, in addition to detect a perturbation of a normal biological state of the heart from the subject. The invention further relates to the medical use and corresponding therapeutic methods based on the individual metabolic cardiac profile of the invention for the heart at physiological state and/or at pathological state. In further aspects, the invention relates to a computer program adapted to execute a mathematical modelling algorithm that will be performed by a computing device/module to produce outputs given data provided as inputs according to preceding claims, wherein said computer program, preferably MATLAB, is written in a programming language selected from a group comprising Fortran, C #, C/C++, High Level Shading Language, or Python.
System and sensor array
The present disclosure provides a system comprising a communication interface and computer for assigning a label to the biomolecule fingerprint, wherein the label corresponds to a biological state. The present disclosure also provides a sensor arrays for detecting biomolecules and methods of use. In some embodiments, the sensor arrays are capable of determining a disease state in a subject.
Method for enrichment and separation of spinal fluid glycoprotein, method for searching for marker for central nervous system diseases which utilizes the aforementioned method, and marker for central nervous system diseases
The purpose of the present invention is to develop: a method for selectively separating a glycoprotein derived from the central nervous system from a body fluid or a central nervous system cell; and a method for searching for an index marker for central nervous system diseases, which utilizes the aforementioned method. A protein derived from the central nervous system, which occurs in a trace amount in a body fluid or a central nervous system cell, can be selectively enriched by a two-stage separation procedure comprising removing a glycoprotein having sialic acid at a non-reducing terminal thereof from the body fluid or the central nervous system cell and then separating a glycoprotein having N-acetylglucosamine at a non-reducing terminal thereof.
MHC-BOUND PEPTIDE ARRAYS AND METHODS OF USE THEREOF
The disclosure provides compositions comprising at least one assembly comprising a peptide and a major histocompatibility complex (MHC), wherein the peptide is an integral component of the MHC, wherein the peptide is attached to a surface at its C-terminus through a linker and wherein the peptide is synthesized on the surface. In certain embodiments, the compositions comprise a plurality of assemblies in a spatially-ordered array. The disclosure provides methods for making and using these compositions.
Method to Map Protein Landscapes
In shotgun proteomics, generally only a fraction of peptides from a parent protein are actually detected. Because a large portion of the protein sequence is not detected, it is often impossible to determine whether the expressed protein is present in a modified, spliced, or truncated form. Provided herein are methods and systems for analyzing polypeptides which allow for the increase of the mean sequence coverage of a protein concomitant with bioinformatics analysis in order to distinguish putative proteoforms with improved amino acid resolution. Aspects of the invention include (1) a deep sequencing strategy to provide more protein sequence coverage than is typically achieved, and (2) a computational approach to view protein expression across its full length and identify regions of the protein that are potentially subject to such regulation. This technology has global utility in proteomics and will be of particular use for the analysis of biosimilar protein drug therapeutics.
PLATELET BIOMARKERS AND DIAGNOSTIC METHODS FOR VASCULAR DISEASES
The present invention relates to biomarkers and diagnostic and prognostic methods for vascular diseases. In particular, proteins of platelet-derived exosomes have been identified as biomarkers that can be used to detect platelet activation associated with pathogenesis of vascular diseases, including cardiovascular and cerebrovascular diseases. The invention also provides compositions for detecting biomarkers as well as compositions and methods useful for treating vascular diseases.