The use of high-dimensional biology (genomics, transcriptomics, proteomics, and metabolomics) to understand the preterm parturition syndrome

Abstract

High-dimensional biology (HDB) refers to the simultaneous study of the genetic variants (DNA variation), transcription (messenger RNA [mRNA]), peptides and proteins, and metabolites of an organ, tissue, or an organism in health and disease. The fundamental premise is that the evolutionary complexity of biological systems renders them difficult to comprehensively understand using only a reductionist approach. Such complexity can become tractable with the use of "omics" research. This term refers to the study of entities in aggregate. The current nomenclature of "omics" sciences includes genomics for DNA variants, transcriptomics for mRNA, proteomics for proteins, and metabolomics for intermediate products of metabolism. Another discipline relevant to medicine is pharmacogenomics. The two major advances that have made HDB possible are technological breakthroughs that allow simultaneous examination of thousands of genes, transcripts, and proteins, etc., with high-throughput techniques and analytical tools to extract information. What is conventionally considered hypothesis-driven research and discovery-driven research (through "omic" methodologies) are complementary and synergistic. Here we review data which have been derived from: 1) genomics to examine predisposing factors for preterm birth; 2) transcriptomics to determine changes in mRNA in reproductive tissues associated with preterm labour and preterm prelabour rupture of membranes; 3) proteomics to identify differentially expressed proteins in amniotic fluid of women with preterm labour; and 4) metabolomics to identify the metabolic footprints of women with preterm labour likely to deliver preterm and those who will deliver at term. The complementary nature of discovery science and HDB is emphasised.

Figure 1.

Mass spectrometry profiles of amniotic fluid from patients with preterm labor who delivered at term (A) and preterm labor with infection/inflammation (B). Reproduced with permission from Romero R, Bujold E, Andrews P. Michigan Proteome Center SU/Perinatology Research Branch.

Figure 2.

MMP-8 rapid test. Reproduced with permission from Nien JK, et al. Am J Obstet Gynecol. 2006;195:1025–30.

Figure 3.

Hierarchical clustering of probe sets that discriminate the chorioamniotic membrane samples of term in labor (TIL) patients from their term no labor (TNL) counterparts. The top 224 probe sets (P% .02) with a minimum average expression difference of 1.4-fold are shown. Reproduced with permission from Haddad et al. Am J Obstet Gynecol 2006;195:394. e1–24.