Proteomic analysis of biological fluids

Abstract

The invention concerns the identification of proteomes of biological fluids and their use in determining the state of maternal/fetal conditions, including maternal conditions of fetal origin, chromosomal aneuploidies, and fetal diseases associated with fetal growth and maturation. In particular, the invention concerns the identification of the proteome of amniotic fluid (multiple proteins representing the composition of amniotic fluid) and the correlation of characteristic changes in the normal proteome with various pathologic maternal/fetal conditions, such as intra-amniotic infection, or chromosomal defects.

1 . A method for predicting pre-term birth in a mammalian subject, comprising:
 (1) comparing the proteomic profile of a test sample of a biological fluid obtained from said mammalian subject with a proteomic profile of a reference sample wherein the test sample proteomic profile and the reference sample proteomic profile comprise information of the expression of at least one of the following: IGFBP-1, Gelsolin precursor, Calgranulin A, Alpha-1-acid glycoprotein 1 precursor, and Alpha-1-antitrypsin precursor; or fragments or naturally occurring variants, and;   (2) predicting pre-term birth in said mammalian subject if:
 (a) at least one unique expression signature of said proteomic profiles differs in said test sample relative to said reference sample wherein said unique expression signature of said reference sample proteomic profile comprises information of the expression of at least one of the following: IGFBP-1, Gelsolin precursor, Calgranulin A, Alpha-1-acid glycoprotein 1 precursor, and Alpha-1-antitrypsin precursor; or fragments or naturally occurring variants, and wherein the reference sample proteomic profile is a normal proteomic profile that is indicative of normal birth; or 
 (b) at least one unique expression signature of said proteomic profiles is essentially the same in said test sample relative to said reference sample wherein said unique expression signature of said reference sample proteomic profile comprises information of the expression of at least one of the following: IGFBP-1, Gelsolin precursor, Calgranulin A, Alpha-1-acid glycoprotein 1 precursor, and Alpha-1-antitrypsin precursor; or fragments or naturally occurring variants thereof, and wherein the reference sample proteomic profile is a proteomic profile that has been predetermined to be indicative of pre-term birth. 
   
     
     
         2 . The method of  claim 1  wherein said IGFBP-1 fragment comprises SEQ ID NO 4. 
     
     
         3 . The method of  claim 1  wherein said test sample and said reference sample proteomic profiles further comprise information of the expression of one or more of the following polypeptides: Calgranulin B, Neutrophil gelatinase-associated lipocalin, Annexin II (Lipocortin II), and Complement C3 precursor; or fragments or naturally occurring variants thereof. 
     
     
         4 . The method of  claim 3  wherein said test sample and said reference sample proteomic profiles further comprise information of the expression of one or more of the following polypeptides: L-plastin (Lymphocyte cytosolic protein 1), Profilin I, Alpha-1-acid glycoprotein 2 precursor, Alpha-1-antichymotrypsin precursor, Ceruloplasmin precursor, Apolipoprotein A-I precursor (Apo-AI), 14-3-3 protein zeta/delta plasma, Vitamin D-binding protein precursor, Serotransferrin, Squamous cell carcinoma antigen 1, 14-3-3 protein sigma (Stratifin), Cystatin A (Stefin A), Fibronectin precursor, Squamous cell carcinoma antigen 2, and Azurocidin; or fragments or naturally occurring variants. 
     
     
         5 . The method of  claim 4  wherein the proteomic profiles are represented in the form of mass spectra. 
     
     
         6 . The method of  claim 5  wherein said mammalian subject is a primate. 
     
     
         7 . The method of  claim 6  wherein said primate is human. 
     
     
         8 . The method of  claim 1  wherein the biological fluid is amniotic fluid or maternal serum. 
     
     
         9 . The method of  claim 1  wherein said proteomic profiles comprise information of the expression of at least 10 proteins. 
     
     
         10 . The method of  claim 1  wherein said proteomic profiles comprise information of the expression of at least 20 proteins. 
     
     
         11 . The method of  claim 1  wherein said proteomic profiles comprise information of the expression of at least 50 proteins. 
     
     
         12 . A method for predicting pre-term birth in a mammalian subject, comprising:
 (1) comparing the proteomic profile of a test sample of a biological fluid with a proteomic profile of a reference sample wherein said test sample proteomic profile and said reference sample proteomic profile comprise information of the expression of IGFBP-1 or fragments or naturally occurring variants thereof, and;   (2) predicting pre-term birth in said mammalian subject if:
 (A) at least one unique expression signature of said proteomic profiles differs in said test sample relative to said reference sample, wherein said unique expression signature of said reference sample proteomic profile comprises information of the expression of IGFBP-1 or fragments or naturally occurring variants thereof; and wherein the reference sample proteomic profile is a normal proteomic profile that is indicative of normal birth; or 
 (B) at least one unique expression signature of said proteomic profiles is essentially the same in said test sample relative to said reference sample wherein said unique expression signature of said reference sample proteomic profile comprises information of the expression of IGFBP-1, or fragments or naturally occurring variants thereof and wherein the reference sample proteomic profile is a proteomic profile that has been predetermined to beindicative of pre-term birth. 
   
     
     
         13 . The method of  claim 1  wherein said IGFBP-1 fragment comprises SEQ ID NO 4. 
     
     
         14 . The method of  claim 13  wherein the proteomic profiles are represented in the form of mass spectra. 
     
     
         15 . The method of  claim 12  wherein said mammalian subject is a primate. 
     
     
         16 . The method of  claim 15  wherein said primate is human. 
     
     
         17 . The method of  claim 12  wherein the biological fluid is amniotic fluid or maternal serum. 
     
     
         18 . The method of  claim 12  wherein said proteomic profiles comprise information of the expression of at least 10 proteins. 
     
     
         19 . The method of  claim 12  wherein said proteomic profiles comprise information of the expression of at least 20 proteins. 
     
     
         20 . The method of  claim 12  wherein said proteomic profiles comprise information of the expression of at least 50 proteins.