In the past two decades, our ability to study cellular and molecular systems has been transformed through the development of omics sciences. While unlimited potential lies within massive omics ...datasets, the success of omics sciences to further our understanding of human disease and/or translating these findings to clinical utility remains elusive due to a number of factors. A significant limiting factor is the integration of different omics datasets (i.e., integromics) for extraction of biological and clinical insights. To this end, the National Cancer Institute (NCI) and the National Heart, Lung and Blood Institute (NHLBI) organized a joint workshop in June 2012 with the focus on integration issues related to multi-omics technologies that needed to be resolved in order to realize the full utility of integrating omics datasets by providing a glimpse into the disease as an integrated "system". The overarching goals were to (1) identify challenges and roadblocks in omics integration, and (2) facilitate the full maturation of 'integromics' in biology and medicine. Participants reached a consensus on the most significant barriers for integrating omics sciences and provided recommendations on viable approaches to overcome each of these barriers within the areas of technology, bioinformatics and clinical medicine. Keywords: Omics integration, Omics science, Clinical application, Risk prediction, Proteomics, Metabolomics, Genomics
1 Cardiology Division and Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts; 2 Department of Pediatrics, University of Colorado Denver and Health ...Sciences, Denver, Colorado; 3 Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee; 4 Mass Spectrometry Research Center, Vanderbilt University Medical Center, Nashville, Tennessee; 5 Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota; 6 Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota; 7 Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts; 8 Cardiovascular Division, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts; and 9 National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
Submitted 24 January 2008
; accepted in final form 27 April 2008
The emerging scientific field of proteomics encompasses the identification, characterization, and quantification of the protein content or proteome of whole cells, tissues, or body fluids. The potential for proteomic technologies to identify and quantify novel proteins in the plasma that can function as biomarkers of the presence or severity of clinical disease states holds great promise for clinical use. However, there are many challenges in translating plasma proteomics from bench to bedside, and relatively few plasma biomarkers have successfully transitioned from proteomic discovery to routine clinical use. Key barriers to this translation include the need for "orthogonal" biomarkers (i.e., uncorrelated with existing markers), the complexity of the proteome in biological samples, the presence of high abundance proteins such as albumin in biological samples that hinder detection of low abundance proteins, false positive associations that occur with analysis of high dimensional datasets, and the limited understanding of the effects of growth, development, and age on the normal plasma proteome. Strategies to overcome these challenges are discussed.
protein content; proteome
Address for reprint requests and other correspondence: L. B. Ware, T1218 MCN, 1161 21st Ave. S, Nashville, TN 37232-2650 (e-mail: lorraine.ware{at}vanderbilt.edu )
Fetuin/α
2
-HS glycoprotein (α
2
-HSG) homologs have been identified in several species including rat, sheep, pig, rabbit, guinea pig, cattle, mouse and human. Multiple physiological roles for these ...homologs have been suggested, including ability to bind to hydroxyapatite crystals and to specifically inhibit the tyrosine kinase (TK) activity of the insulin receptor (IR). In this study we report the identification, cloning, and characterization of the mouse Ahsg gene and its function as an IR-TK inhibitor. Genomic clones derived from a mouse Svj 129 genomic library were sequenced in order to characterize the intron–exon organization of the mouse Ahsg gene, including an 875 bp subclone containing 154 bp upstream from the transcription start site, the first exon, and part of the first intron. A second genomic subclone harboring a 3.45 kb Bgl II fragment contained exons 2, 3 and 4 in addition to two adjacent elements within the first intron-a repetitive element of the B1 family (92 bp) and a 271 bp tract of (T,C)
n
* (A,G)
n
. We have mapped mouse Ahsg at 16 cM adjacent to the Diacylglycerol kinase 3 (Dagk3) gene on chromosome 16 by genotyping interspecific backcross panels between C57BL/6J and
Mus spretus
. The position is syntenic with human chromosome 3q27, where the human AHSG gene resides. Using recombinant mouse α
2
-HSG expressed from a recombinant baculovirus,
we demonstrate that mouse α
2
-HSG inhibits insulin–stimulated IR autophosphorylation and
IR-TKA
in vitro
. In addition, mouse α
2
-HSG (25μg/ml) completely abolishes insulin-induced
DNA synthesis in H-35 rat hepatoma cells. Based on
the sequence data and functional analysis, we conclude
that the mouse Ahsg gene is the true ortholog
of the human AHSG gene.
Fetuin/ alpha sub(2)-HS glycoprotein ( alpha sub(2)-HSG) homologs have been identified in several species including rat, sheep, pig, rabbit, guinea pig, cattle, mouse and human. Multiple ...physiological roles for these homologs have been suggested, including ability to bind to hydroxyapatite crystals and to specifically inhibit the tyrosine kinase (TK) activity of the insulin receptor (IR). In this study we report the identification, cloning, and characterization of the mouse Ahsg gene and its function as an IR-TK inhibitor. Genomic clones derived from a mouse Svj 129 genomic library were sequenced in order to characterize the intron-exon organization of the mouse Ahsg gene, including an 875 bp subclone containing 154 bp upstream from the transcription start site, the first exon, and part of the first intron. A second genomic subclone harboring a 3.45 kb Bgl II fragment contained exons 2, 3 and 4 in addition to two adjacent elements within the first intron-a repetitive element of the B1 family (92 bp) and a 271 bp tract of (T,C)n * (A,G)n. We have mapped mouse Ahsg at 16 cM adjacent to the Diacylglycerol kinase 3 (Dagk3) gene on chromosome 16 by genotyping interspecific backcross panels between C57BL/6J and Mus spretus. The position is syntenic with human chromosome 3q27, where the human AHSG gene resides. Using recombinant mouse alpha sub(2)-HSG expressed from a recombinant baculovirus, we demonstrate that mouse alpha sub(2)-HSG inhibits insulin-stimulated IR autophosphorylation and IR-TKA in vitro. In addition, mouse alpha sub(2)-HSG (25 mu g/ml) completely abolishes insulin-induced DNA synthesis in H-35 rat hepatoma cells. Based on the sequence data and functional analysis, we conclude that the mouse Ahsg gene is the true ortholog of the human AHSG gene.
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