Multi-Omics Research: Traversing the Central Dogma of Molecular Biology
The availability of extensive microbial genome sequence information for even complex environmental samples has enabled systems biology interrogation of microbial communities such as the human microbiome. Our current research seeks to develop and demonstrate advanced “shotgun” mass spectrometry techniques for the comprehensive characterization of microbial metaproteomes in order to examine the metabolic activities of these interwoven micro-ecosystems. Recent work has focused on improved methods for cellular lysis and proteome extraction, coupled with automated multi-dimensional LC-MS/MS on QExactive mass spectrometric systems. This has been coupled with improvements in our data analysis/data mining pipeline for enhancing peptide/protein identification and quantification. The objective of this work is to employ a high performance multi-dimensional LC-MS/MS based metaproteomic approach to examine microbiome temporal functional shifts during microbial colonization of the preterm human infant gut. In particular, fecal metaproteomes of 94 preterm infant samples, each collected at discrete time-points over several months, were measured by LC-MS/MS and yielded identification of tens of thousands of proteins, many of which corresponded to enzymes that mapped onto a large and deeply interconnected network of metabolic reactions. Tracking metabolic function rather than discrete proteins has the potential of revealing how microbial metabolic function progresses across development of the preterm human infant gut microbiome, and how the overall metabolic potential of the system expands or contracts temporally. The time-course metaproteomics measurements revealed core metabolic pathways in both human and microbial proteins, indicating the establishment of the mutualistic relationship between the microbiome and human host early in infancy. In total, these results reveal functional stability and inter-individual signatures of the preterm infant gut microbiome.
Advances in mass spectrometry-based methods have enabled deeper biological insights using proteomics and metabolomics approaches. This has also resulted in improvements in our ability to compare and correlate these data with other ‘omics methods such as genomics and transcriptomics—thus creating the new field of multi-omics.
In this session, experts will present their work in the area of multi-omics research. Robert Hettich (Oak Ridge National Laboratory) will present his experiences with integrating advanced mass spectrometry technology and meta-omics analysis for characterizing complex microbiomes. Kelly Ruggles (NYU Langone Health) will discuss ways to integrate the results from diverse experiments and develop complementary statistical analysis methods for large comprehensive proteogenomics datasets. Ewy Mathé (Ohio State University) will cover analytical methods in genomics, epigenomics, and metabolomics to characterize disease biomarkers and therapeutic targets. Lastly, Tejaswini Mishra (Stanford University) will tell of her work in multi-omics profiling.
The presentations will be followed by a panel discussion that will address challenges and solutions for adopting multi-omics methods in core facility settings.
