The method presented herein includes acquiring a mass spectrum of a molecule that includes mass spectrum peaks corresponding to a precursor ion and fragment ions. The method also includes identifying at least a portion of the fragment ions in the mass spectrum as corresponding to one or more monomer subunit ion of the precursor ion by appending one or more of the fragment ions to an inferable constituent to produce a topology building block. The topology building block is then stored in a candidate pool as corresponding to one or more of the monomer subunit ion if the combined mass of the inferable constituent and one or more of the fragment ions satisfy a first user-defined mass tolerance. One or more candidate topology of the precursor ion is then obtained by combining a plurality of the topology building blocks that satisfy a second user-defined mass tolerance for the precursor ion.

The present invention relates to biomarkers of lung cancer, particularly to markers that enable distinguishing between subtypes of non-small cell lung cancer (NSCLC), particularly between adenocarcinoma (AC) and squamous cell carcinoma (SCC). In particular, the present invention relates to means and methods for diagnosing, assessing the level of severity and selecting methods of treating NSCLC.

The disclosed methods are directed to detecting polypeptide fragments (“clips”) of parental polypeptides. Parental polypeptides and clips are optionally denatured and then fractionated using a matrix. After a first elution (high molecular weight fraction), an additional elution step retrieves a low molecular weight fraction containing clips. If the clips are an appropriate size for the targeted detection method, such as mass spectrometry, then analysis of this fraction proceeds separately from the high molecular weight fraction, or the clips fraction is mixed with the proteolyzed high molecular weight fraction before analysis. However, if the clips are too large for the intended analytical method(s), then the clips are also proteolyzed. The digested high molecular weight and low molecular weight fractions can be analyzed separately or combined. Analysis of combined samples favors clip quantitation because the clips are analyzed together with the remaining counterpart of the parental polypeptide.

Bead arrays suitable for analysis by mass spectrometry are disclosed. In an embodiment, a bead array includes multiple reactive sites, each of the reactive sites being capable of binding multiple distinct target analytes.

The present disclosure provides methods for site-selectively crosslinking payloads to antibodies and other proteins. This can be accomplished using traceless affinity labels designed to label target proteins with bio-orthogonally reactive entities (ORE) using the compositions and methods described herein.

Provided are multiplexed methods for characterizing binding of a test compound to different receptor target molecules using mass spectroscopy techniques. The methods employ receptor molecules that have different functions or found in different tissues, such as cerebral cortex, cerebellum, ventricular and hepatic membrane preparations. The methods enable determination of undesirable off-target binding of a test compound. The methods comprise incubation of a heterologous mixture of different receptor target molecules with ligands (known binders), and a test compound. Various wells contain different amounts of molecules for use in construction of concentration curves. Next, unbound ligands are separated from the well contents. Next, ligands that were bound to the receptors are separated. An LC/ESI-MS/MS method may be used to reduce irrelevant mass spectroscopy peaks. Binding of the test compound to a desired receptor target molecule is compared to binding of the test compound to other receptor target molecules, i.e., off-target binding.

The present disclosure provides a marker that shows a relationship with changes in the nerve density and morphology in the cornea. In one aspect, the present invention provides a marker for neuropathy in the eye, the expression of which changes in correlation with morphological parameters of the nerves in the eye. In some embodiments, the parameter may include at least one parameter selected from the group consisting of CNBD, CTBD, CNFD, CNFL, and tortuosity. In a particular embodiment, the parameter may include at least one parameter selected from CNBD and CTBD.

Provided is a method for accurate quantification of a HER2 protein in a breast cancer tissue sample by mass spectrometry and a HER2 scoring based thereon. A method according to the presently claimed subject matter is accurate and can make reproducible measurement compared to conventional methods. If possible, personalized therapy according to the method of the presently claimed subject matter can prolong lives of the patients and exceptionally reduce the socioeconomic cost nationwide.

The disclosure relates to a diazirine precursor mass tag compound represented by structural formula (I)

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Also disclosed is a method for detecting analytes in a sample, comprising derivatizing the analytes with the compound of formula (I), and detecting the resulting derivatized analytes by a mass or ion mobility spectrometry.

The present invention relates to a novel analytical method for detecting one or more analytes in a source sample by continuous flow 2D LC-MS/MS using a single LC system.