Provided herein are methods and kits for analyzing a biological sample obtained from a subject having, suspected of having, or being at risk for a disease associated with the contact activation system.

An external standard solution for use in the analysis of amino acid in plasma, containing, (1) at least one amino acid selected from the following components A, at a concentration of 0.0007 M to 0.49 M, and (2) (i) at least one amino acid selected from the following components B, at a concentration of 0.2 to 0.9 times of the lowest-concentration amino acid among the amino acids selected from components A, (ii) at least one amino acid selected from the following components C, at a concentration of 0.1 to 0.4 times of the lowest-concentration amino acid among amino acids selected from the components A, or (iii) at least one amino acid selected from the following components D, at a concentration of 0.05 to 0.2 times of the lowest-concentration amino acid among amino acids selected from the components A; [Components A] valine, glycine, alanine and glutamine [Components B] serine, proline, threonine, taurine, leucine, isoleucine, lysine, histidine, phenylalanine and tyrosine [Components C] asparagine, ornithine, arginine and tryptophan [Components D] glutamic acid, methionine, citrulline and cystine.

An evaluating method includes an evaluating step of evaluating a future risk of lifestyle-related disease for a subject to be evaluated using a concentration value of an amino acid included in amino acid concentration data on the concentration value of the amino acid in blood collected from the subject.

A novel method of diagnosing cystic fibrosis in a human subject is provided. The method includes the steps of: i) determining in a biological sample from the subject the level of one or more metabolic biomarkers; ii) comparing the level of the biomarker to a control level and determining the difference between the biomarker level and the control level; and iii) determining that the subject has cystic fibrosis or a related disorder when the difference in the level of the biomarker in the sample is statistically different from the control level.

The present invention provides a method for the analysis of a compound with amino group (e.g., an amino acid or peptide) contained in a sample and convenient manner with a high sensitivity. The compound with amino group in a sample containing the compound with amino group is labeled with a specific carbamate compound such as p-trimethylammonium anilyl-N-hydroxysuccinimidyl carbamate iodide to enhance the selectivity and sensitivity. The present invention is preferably used in conjunction with mass spectrometry such as MS/MS method to facilitate quantitative analysis. The present invention further provides labeling reagents for mass spectrometry.

An external standard solution for use in the analysis of amino acid in plasma, containing, (1) at least one amino acid selected from the following components A, at a concentration of 0.0007 M to 0.49 M, and (2) (i) at least one amino acid selected from the following components B, at a concentration of 0.2 to 0.9 times of the lowest-concentration amino acid among the amino acids selected from components A, (ii) at least one amino acid selected from the following components C, at a concentration of 0.1 to 0.4 times of the lowest-concentration amino acid among amino acids selected from the components A, or (iii) at least one amino acid selected from the following components D, at a concentration of 0.05 to 0.2 times of the lowest-concentration amino acid among amino acids selected from the components A; [Components A] valine, glycine, alanine and glutamine [Components B] serine, proline, threonine, taurine, leucine, isoleucine, lysine, histidine, phenylalanine and tyrosine [Components C] asparagine, ornithine, arginine and tryptophan [Components D] glutamic acid, methionine, citrulline and cystine.

The present invention relates to systems, kits, and methods for identifying subjects with increased levels (e.g., in a urine sample) of at least two urine metabolites selected from: butanal; 2-Hydroxy-1,3-dimethoxy-8,9-methylenedioxycoumestan; 6-Methylmercaptopurine; Dimethyl-L-arginine; N-butanoyl-lhomoserine lactone; Hexanoylglycine; Methyl propenyl ketone; Ferulate; 2-Oxoarginine; and 2-Hydroxyestradiol-3-methyl ether, as well as methods of determining if a subject has or is at risk of urinary stone disease based on such urine metabolites. In certain embodiments, the urinary tract of a subject with elevated levels of at least two of the urine metabolites is imaged (e.g., to generate an image showing the size, location, or number of urinary stones present).

The present disclosure relates to a panel of a plurality of metabolite species that is useful for the identification or detection of subjects having pancreatic cancer, including methods for identifying such metabolic biomarkers within biological samples. The disclosure also includes a statistical model for predicting the presence of pancreatic cancer in a subject's biofluid by quantifying and comparing positive and negative fold changes in metabolite species' concentration; comparing the subject's metabolite species' concentrations to a predetermined value.

The present invention relates to the discovery that an increased fraction of albumin is carbamylated in patients suffering from kidney disease (e.g., end-stage renal disease) and that the fraction of carbamylated albumin is also correlated with increased disease severity, particularly risk of mortality. The present invention also relates to the discovery that free amino acids can reduce carbamylation of albumin. Based on these discoveries the present invention provides diagnostic and prognostic methods for patients suffering from, or suspected of suffering from kidney disease. The invention also provides methods for treating kidney disease by administration of a compound or composition that reduced protein carbamylation, such as free amino acids or dipeptides.

Adenomyosis is a highly prevalent yet enigmatic disease that can be diagnosed only via histopathology among women undergoing hysterectomy, thus, leading to underdiagnosis. Unfortunately, research on adenomyosis has been limited due to a variety of challenges, and little work has been done on non-invasive diagnostics for adenomyosis. Currently, there is no FDA-approved non-invasive method for early detection of adenomyosis. By integrating immunoassays and metabolomics analyses, candidate biomarkers for the non-invasive diagnosis of adenomyosis in cervicovaginal lavages have been identified. Thus, methods for non-invasive diagnostic, screening, and early detection of adenomyosis in patients are described herein.