The United States of America, As Represented by the Secretary, Department of Health and Human Services

The United States of America As Represented by the Department of Health

Malcolm Moos, Jr

Frank P Luyten

Shouwen Wang

Bang Hoang

Steven Chao-Huan Chang

Frank Luyten

Elaine Ellen Thompson

Marie Krinks

Vahan Simonyan

Methods are disclosed for clustering biological samples and other objects using a grand canonical ensemble. A biological sample is characterized by data attributes from varying sources (e.g. NGS, other types of high-dimensional cytometric data, observed disease state) and of varying data types (e.g. Boolean, continuous, or coded sets) organized as vectors (as many as 10) having as many as 10, 10, or more components. The biological samples or observational data are modeled as particles of a grand canonical ensemble which can be variably distributed among partitions. A pseudo-energy is defined as a measure of inverse similarity between the particles. Minimization of grand canonical ensemble pseudo-energy corresponds to clustering maximally similar particles in each partition, thereby determining clusters of the biological samples. The sample clusters can be used for feature discovery, gene and pathway identification, and development of cell based therapeutics, or for other purposes. Variations and additional applications are disclosed.

Clustering methods using a grand canonical ensemble

An isolated cDNA encoding a growth-inducing protein, Frzb, capable of stimulating bone, cartilage, muscle and nerve tissue formation. Frzb binds to and modulates the activity of Wnt growth factors which play a role in various developmental and neoplastic processes. The cDNA and protein sequences of human, bovine andFrzb are provided. Production and purification of recombinant Frzb are also described.

Method of modulating tissue growth using Frzb protein

Nucleotide and amino acid sequences of cartilage-derived morphogenetic proteins (CDMP-1 and CDMP-2) from human and bovine cartilage extracts. These proteins exhibit chondrogenic activity and can be used to repair cartilage defects in a mammal.

Cartilage-derived morphogenetic proteins

The present invention is a purified cartilage extract that stimulates local cartilage formation when combined with a matrix and implanted into a mammal. This extract can conveniently be produced by a method which includes the steps of: obtaining cartilage tissue; homogenizing the cartilage tissue in the presence of chaotropic agents under conditions that permit separation of proteins from proteoglycans; separating the proteins from the proteoglycans and then obtaining the proteins. The step for separating the proteins from the proteoglycans can be carried out using a sepharose column. The extract can also be obtained by additionally including the steps of separating the proteins on a molecular sieve and then collecting the proteins having molecular weights in the 30 kDa to 60 kDa size range. Articular cartilage or epiphyseal cartilage can be used in the preparation of this purified extract.

DNA molecules encoding cartilage-derived morphogenetic proteins

Isolation and method of using tissue growth-inducing Frzb protein

An isolated cDNA encoding a growth-inducing protein, Frzb, capable of stimulating bone, cartilage, muscle, and nerve tissue formation. Frzb binds to and modulates the activity of Wnt growth factors which play a role in various developmental and neoplastic processes. The cDNA and protein sequences of human, bovine andFrzb are provided. Production and purification of recombinant Frzb are also described.

Method of modulating tissue growth using Frzb Protein

An isolated cDNA encoding a growth-inducing protein, Frzb, capable of stimulating bone, cartilage, muscle and nerve tissue formation. The CDNA and protein sequences of human and bovine frzb are provided. Production and purification of recombinant Frzb are also described.

Isolation and use of tissue growth-inducing Frzb protein

An isolated polynucleotide of anti-dorsalizing morphogenetic protein (ADMP-1) is obtained from Xenopus. The protein is most closely related to human BMP-3. ADMP-1 functions as a modulator for dorsalizing influences, and prevents syndromes involving inappropriate proliferation of tissues.

Growing community of inventors

Bethesda, MD, United States of America

Malcolm Moos, Jr