Markers of acute myeloid leukemia stem cells (AMLSC) are identified. The markers are differentially expressed in comparison with normal counterpart cells, and are useful as diagnostic and therapeutic targets.

The invention provides compositions and methods for binding Ras in a nucleotide free state (apo RAS) and inhibiting Ras signaling. In one embodiment, the invention provides monobodies that specifically bind apo RAS and methods of use. Thus, in diseases and conditions where a reduction of Ras signaling is beneficial, such inhibitory compositions act as therapeutics.

Systems and methods to identify new protein targets of a chemical compound or its derivatives were described. The methods can be used for detection of new binding partners as long as the chemical compound can covalently bind to the protein targets. Once protein targets are resolved, information related to new protein targets can then be used to couple with real-world patient data such as adverse events, efficacy data, and disease correlation data to deduce real-world evidence. Systems collectively with all this information can aide clinical development and use of pharmaceutical drug. Methods are provided for detection of covalently bound phenyl vinyl sulfone (PVS) or its derivatives, and afatinib or its derivatives. Furthermore, generation of antiserum recognizing carrier bound PVS or carrier bound afatinib is described. PRMT1 is described as a new target of PVS and RRM1, RRM2, and NFKB are described as new targets of afatinib.

Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease.

The invention relates to a method for preparing PHFs-like Tau aggregates and to a method for identifying compounds that are inhibitors of Tau protein aggregation, blockers of Tau seeding and propagation, and imaging agents that specifically bind PHF.

This disclosure provides isolated or recombinant polypeptides that are useful to vaccinate individuals suffering from chronic/recurrent biofilm disease or as a therapeutic for those with an existing infection. The individual's immune system will then naturally generate antibodies which prevent or clear these bacteria from the host by interfering with the construction and or maintenance of a functional protective biofilm. Alternatively, antibodies to the polypeptides can be administered to treat or prevent infection. Bacteria that cannot form functional biofilms are more readily cleared by the remainder of the host's immune system and/or traditional antibiotics.

Plasma kallikrein binding proteins and methods of using such proteins are described.

The present invention relates to methods and compositions for treating and/or preventing a disease or disorder associated with abnormally high level of the IFP35 family of proteins, including IFP35 and NMI, methods and compositions for diagnosis, prognosis or treatment monitoring of a disease or disorder associated with abnormally high level of the IFP35 family of proteins, including IFP35 and NMI, and methods and compositions for identifying a modulator of the IFP35 family of proteins, including IFP35 and NMI.

It has been revealed that, from a pre-onset stage of Alzheimer's disease, enhancement of phosphorylations of MARCKS and the like causes abnormal spine formation or the like, consequently developing the disease. Moreover, it has also been revealed that the phosphorylations of MARCKS and the like are caused by PKC and the like, and further that b-raf is involved in the phosphorylation of a tau protein important for the progression of Alzheimer's disease. Thus, these proteins have been found to be target molecules useful in the diagnosis and treatment of Alzheimer's disease. In addition, it has also been revealed that, pre-onset in a stage of frontotemporal lobar degeneration also, b-RAF phosphorylation enhancement causes a decrease in the number of spines and the like, consequently developing the disease. Thus, b-RAF has been found to be a target molecule useful in the diagnosis and treatment of frontotemporal lobar degeneration.

The invention provides methods and compositions for identifying binding polypeptides (e.g., antibodies or antigen binding fragments thereof) that specifically binds to a cell-surface antigen. The methods of the invention generally comprise contacting a variegated nucleic acid-display library of binding polypeptides with a cell-surface antigen displayed on the exterior surface of a cell; and isolating from the library at least one library member that specifically binds to the cell-surface antigen on the exterior surface of the cell.