The Human Plasma Proteome History, Character, and Diagnostic Prospects

The present invention provides methods for enhanced detection of biological response patterns. In one embodiment of the invention, genes are grouped into basis genesets according to the co-regulation of their expression. Expression of individual genes within a geneset is indicated with a single gene expression value for the geneset by a projection process. The expression values of genesets, rather than the expression of individual genes, are then used as the basis for comparison and detection of biological response with greatly enhanced sensitivity. In another embodiment of the invention, biological responses are grouped according to the similarity of their biological profile. The methods of the invention have many useful applications, particularly in the fields of drug development and discovery. For example, the methods of the invention may be used to compare biological responses with greatly enhanced sensitivity. The biological responses that may be compared according to these methods include responses to single perturbations, such as a biological response to a mutation or temperature change, as well as graded perturbations such as titration with a particular drug. The methods are also useful to identify cellular constituents, particularly genes, associated with a particular type of biological response. Further, the methods may also be used to identify perturbations, such as novel drugs or mutations, which effect one or more particular genesets. The methods may still further be used to remove experimental artifacts in biological response data.

Methods for using co-regulated genesets to enhance detection and classification of gene expression patterns

The human plasma proteome

http://plasmaproteome.com/Papers/The%20Plasma%20Proteome%20Anderson%20and%20Anderson%20as%20printed%20corr1.pdf

History, character, and diagnostic prospects*

Twenty-three of the most prominent spots which are visible on two-dimensional (2-D) protein gels of Bacillus subtilis crude extracts were selected as marker spots for the construction of a 2-D protein index. N-terminal sequencing of the corresponding proteins resulted in the identification of enzymes involved in glycolysis, TCA cycle, pentose phosphate cycle, amino acid metabolism, nucleotide biosynthesis and translation. Using computer analysis of the 2-D protein gels, most of these metabolic enzymes were found to be synthesized at a reduced rate after different stresses and glucose starvation. Such an approach permits a rapid and global evaluation of the regulation of different branches of metabolism in response to various physiological conditions.

/pdf/identification-of-vegetative-proteins-for-a-two-dimensional-5b9kqv9p64.pdf

Identification of vegetative proteins for a two-dimensional protein index of Bacillus subtilis

The Protein Disease Database (PDD) is a relational database of proteins and diseases. With this database it is possible to screen for quantitative protein abnormalities associated with disease states. These quantitative relationships use data drawn from the peer-reviewed biomedical literature. Assays may also include those observed in high-resolution electrophoretic gels that offer the potential to quantitate many proteins in a single test as well as data gathered by enzymatic or immunologic assays. We are using the Internet World Wide Web (WWW) and the Web browser paradigm as an access method for wide distribution and querying of the Protein Disease Database. The WWW hypertext transfer protocol and its Common Gateway Interface make it possible to build powerful graphical user interfaces that can support easy-to-use data retrieval using query specification forms or images. The details of these interactions are totally transparent to the users of these forms. Using a client-server SQL relational database, user query access, initial data entry and database maintenance are all performed over the Internet with a Web browser. We discuss the underlying design issues, mapping mechanisms and assumptions that we used in constructing the system, data entry, access to the database server, security, and synthesis of derived two-dimensional gel image maps and hypertext documents resulting from SQL database searches.

The protein disease database of human body fluids. ii: computer methods and data issues

We are developing a relational database to facilitate quantitative and qualitative comparisons of proteins in human body fluids in normal and disease states For decades researchers and clinicians have been studying proteins in body fluids such as serum, plasma, cerebrospinal fluid and urine Currently, most clinicians evaluate only a few specific proteins in a body fluid such as plasma when they suspect that a patient has a disease Now, however, high resolution two-dimensional protein electrophoresis allows the simultaneous evaluation of 1,500 to 3,000 proteins in complex solutions, such as the body fluids This and other high resolution methods have encouraged us to collect the clinical data for the body fluid proteins into an easily accessed database For this reason, it has been constructed on the Internet World Wide Web (WWW) under the title Protein Disease Database (PDD) In addition, this database will provide a linkage between the disease-associated protein alterations and images of the appropriate proteins on high-resolution electrophoretic gels of the body fluids This effort requires the normalization of data to account for variations in methods of measurement Initial efforts in the establishment of the PDD have been concentrated on alterations in the acute-phase proteins in individuals with acute and chronic diseases Even at this early stage in the development of our database, it has proven to be useful as we have found that there appear to be several common acute-phase protein alterations in the plasma and cerebrospinal fluid from patients with Alzheimer's disease, schizophrenia and major depression Our goal is to provide access to the PDD so that systematic correlations and relationships between disease states can be examined and extended

The protein disease database of human body fluids: I. Rationale for the development of this database.

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The protein disease database of human body fluids. ii: computer methods and data issues

The protein disease database of human body fluids: I. Rationale for the development of this database.