The present invention relates to new methods for assessing the risk of a patient, in particular with chronic liver disease, to develop primary liver cancer over time, using functions combining blood biochemical markers.

The invention relates to the use of an immunologically reactive microbial transglutaminase or its immunologically reactive parts or analogues, which are present in a complex with gliadin or its immunologically reactive parts or analogues, for the diagnosis and/or therapy control of coeliac disease or sprue as well as gluten sensitivity, and a kit for determining the diagnosis and/or therapy control of coeliac disease or sprue as well as of gluten sensitivity, by means of the previously mentioned complex.

The present invention relates to a method for identifying a MYCBP2 modulator. Suitable modulators are identified by modulation of MYCBP2 ubiquitin E3 ligase activity via covalent modification of either of two catalytic cysteines (C4520 and C4572) or by impeding the motion of a newly presented dynamic, so-called, mediator loop region where C4520 resides. The present invention also relates to the use of hydroxy group- containing small molecules and peptides as proxy substrates for measuring MYCBP2 ligase activity and their use in the method of identifying modulators.

Cells within liver tumor mass comprise a unique set of proteins/tumor antigens when compared to the normal liver tissues epithelial cells juxtaposed to the tumor. The presence of tumor antigens couples the production of auto-antibodies against these tumor antigens. The present invention relates to the identification and elucidation of a protein set that can act as a novel marker set for liver cancer diagnosis and prognosis. Specifically, it relates to a kit that enables diagnostic and prognostic measurement of auto-antibodies in serum of liver cancer patients. The present invention provides a non-invasive, specific, sensitive, and cost effective detection and quantification method by evaluating a set of validated liver cancer proteins/tumor antigens, which includes Bmi-1, VCC1, SUMO-4, RhoA, TXN, ET-1, UBE2C, HDGF2, FGF21, LECT2, SOD1, STMN4, Midkine, IL-17A, IL26, or DCP to complement the conventional diagnostic methods.

Heritable mutations in the BRCA1 and BRCA2 and other genes in the DNA double-strand break (DSB) repair pathway increase risk of breast, ovarian and other cancers. In response to DNA breaks, the proteins encoded by these genes bind to each other and are transported into the nucleus to form nuclear foci and initiate homologous recombination. Flow cytometry-based functional variant analyses (FVAs) were developed to determine whether variants in BRCA1 or other DSB repair genes disrupted the binding of BRCA1 to its protein partners, the phosphorylation of p53 or the transport of the BRCA1 complex to the nucleus in response to DNA damage. Each of these assays distinguished high-risk BRCA1 mutations from low-risk BRCA1 controls. Mutations in other DSB repair pathway genes produced molecular phenocopies with these assays. FVA assays may represent an adjunct to sequencing for categorizing VUS or may represent a stand-alone measure for assessing breast cancer risk.

Heritable mutations in the BRCA1 and BRCA2 and other genes in the DNA double-strand break (DSB) repair pathway increase risk of breast, ovarian and other cancers. In response to DNA breaks, the proteins encoded by these genes bind to each other and are transported into the nucleus to form nuclear foci and initiate homologous recombination. Flow cytometry-based functional variant analyses (FVAs) were developed to determine whether variants in BRCA1 or other DSB repair genes disrupted the binding of BRCA1 to its protein partners, the phosphorylation of p53 or the transport of the BRCA1complex to the nucleus in response to DNA damage. Each of these assays distinguished high-risk BRCA1 mutations from low-risk BRCA1 controls. Mutations in other DSB repair pathway genes produced molecular phenocopies with these assays. FVA assays may represent an adjunct to sequencing for categorizing VUS or may represent a stand-alone measure for assessing breast cancer risk.

Disclosed herein are compounds, compositions, and methods for identifying substrates of E3 ubiquitin ligases. The proteins, vectors, compositions, and may be utilized in methods for orthogonal ubiquitin transfer (OUT) between variant components of the ubiquitin cascade such as a variant ubiquitin (UB), a variant ubiquitin activating enzyme (E1), a variant ubiquitin-conjugating enzyme (E2), and a variant ubiquitin ligase (E3), which may include a variant HECT type, U-box type, RBR type, and/or Ring type E3 ligase. The variant components of the ubiquitin cascade typically include one or more mutations relative to their wild-type counterparts, such as amino acid substitutions, such that the variant components interact specifically and orthogonally with each of their variant components and do not interact with the wild-type counterpart of their variant components.

The present invention relates to the production of activated biological molecules for use in profiling biological molecule interactions. The activated biological molecule may be a ubiquitin (Ub) and ubiquitin-like conjugation enzyme as well as other proteins with internal reactive cysteine residues.

Cells within liver tumour mass comprise a unique set of proteins/tumour antigens when compared to the normal liver tissues epithelial cells juxtaposed to the tumour. The presence of tumour antigens couples the production of auto-antibodies against these tumour antigens. The present invention relates to the identification and elucidation of a protein set that can act as a novel marker set for liver cancer diagnosis and prognosis. Specifically, it relates to a kit that enables diagnostic and prognostic measurement of auto-antibodies in serum of liver cancer patients. The present invention provides a non-invasive, specific, sensitive, and cost effective detection and quantification method by evaluating a set of validated liver cancer proteins/tumour antigens, which includes Bmi-1, VCC1, SUMO-4, RhoA, TXN, ET-1, UBE2C, HDGF2, FGF21, LECT2, SOD1, STMN4, Midkine, IL-17A or IL26, to complement the conventional diagnostic methods.

The present invention concerns enriched heterogeneous mammalian renal cell populations characterized by biomarkers, and methods of making and using the same.