Our full integration of biology is based on the central dogma of biology. This concept states that genetic code is encoded in DNA, which is transcribed to RNA, which is then subsequently translated to proteins. Proteins are the major structural components of cells, tissues and organs. Metabolites are small molecules that are found both in the intracellular and the extracellular space.

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            Accordingly, our full integration of biology is a practical implementation of the central dogma, where we assess all “omics” simultaneously: genomics, methylomics, transcriptomics, proteomics, glycoproteomics, metabolomics, lipidomics, and the bacterial microbiome. Measurements from each of these “omics” assessments are then integrated into functional insights that provide a roadmap for individual health, wellness, and longevity.

 

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Genomics

 

                We perform whole genome sequencing (WGS) using short-read or long-read sequencing technologies. The human genome contains approximately 6.4 billion nucleotides, of which half of them came from the mother and half of them came from the father. The coding region of the genome that gets translated into proteins is approximately only 1% of the entire human genome, referred to as the exome. The rest of the genome, the remaining 99%, is referred to as the entrance, and these regions of DNA do not get transcribed and translated into proteins. Rather, these are regulatory regions of the genome. When we perform WGS, we typically identify approximately 5 million variants in each individual that are different from the population reference. We curate these individual variants against well-established genomic databases. We assess both the functional consequence of each variant, or mutation, such as loss-of function, etc. We also assess potential clinical relevance of these mutations when known, and classify known variants as pathogenic, likely pathogenic, or variant of uncertain significance. We also report out polygenic risk scores for over 30 common conditions, as well as a full, clinical grade pharmacogenomic report.

 

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DNA Methylation

 

                DNA methylation is a fundamental function in genomic regulation that is critical in embryonic development, as well as in the regulation of genes throughout life. Nucleotides in the DNA can become methylated over time, and the methylation status of nucleotides can turn some genes off and can turn some genes on. DNA methylation plays a crucial role in aging, cardiovascular disease, cancer, etc.

                We assess approximately a million methylation sites within DNA and curate DNA methylation information from applicable databases and from scientific literature. We also interpret DNA methylation data in light of proteomic data (see below).

 

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Proteomics

 

                The human proteome contains approximately 20,000 proteins and we measure, quantify and benchmark approximately 8,000 proteins against a proprietary population reference. We evaluate upregulated and downregulated proteins in the context of genetic variants, as described above.

 

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Glycoproteomics

 

                Proteins are modified over time through a process called glycosylation, where very specific enzymes attach very specific glycan molecules to specific amino acid residues within proteins in a very specific sequence. We evaluate glycosylation of immunoglobulins in our projects. Glycosylation status of specific proteins are associated with aging, cardiovascular disease, cancer, autoimmune diseases, etc.

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Metabolomics and Lipidomics

 

                Metabolomics and lipidomics refer to the quantification of metabolites and lipid species, respectively. Metabolites include amino acids, peptides, hormones, vitamins, etc. The human body contains approximately 600 canonical metabolic pathways, such as glycolysis, gluconeogenesis, the citric acid cycle, etc. We measure approximately 1,000 metabolites and lipid species in the human body. We benchmark each metabolite and lipid species against a proprietary database and annotate increased and decreased levels of metabolites and lipids. Furthermore, we integrate metabolomic and lipidomic data in the context of genomic measurements, DNA methylation, and proteomic data (see MULTIOMIC INTEGRATION BELOW).

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                Multiomic integration is part of our core expertise and core technology. Based on the platforms and intellectual property we developed in our biotechnology companies, we are the leading group in the world to integrate multiomic data at the raw data level, applied not in populations, but in individuals. We perform multiomic integration at multiple levels. First, we perform gene-ontology based integration and identify specific molecular networks that are associated with specific tissues, organs and phenotypes at an individual level. Second, we integrate genomic data, methylation data and proteomic data with metabolomic and lipid species data across all human canonical metabolic pathways. This allows us to understand whether specific metabolic abnormalities are due to inherited, genetic factors, or due to environmental factors.

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                We developed imaging protocols based on the combination of conventional X-ray imaging, ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) that specifically look for the top threats and phenotypes that are associated with health, wellness and longevity.

 

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