SZA Longevity

Whole
Genome
Sequencing

Whole-genome sequencing (WGS) is a comprehensive method for analyzing entire genomes. Genomic information has been instrumental in identifying inherited disorders, characterizing the mutations that drive cancer progression, and tracking disease outbreaks. Rapidly dropping sequencing costs and the ability to produce large volumes of data with today’s sequencers make whole-genome sequencing a powerful tool for genomics research.

How is a
Whole
Genome
Sequencing
test done?

Whole Genome Sequencing uses a massively parallel DNA sequencing technology called Next-Generation Sequencing (NGS). In contrast to earlier sequencing technologies (e.g. Sanger sequencing), it enables large scale sequencing of many short DNA molecules at the same time. This is much faster than sequencing the full length of the entire genome base-by-base. To determine the order of the short DNA fragments that are output by the sequencing machines, the fragments are computationally mapped to a reference genome and the full-length DNA strands of the newly sequenced genome are reconstructed. When comparing Whole Genome Sequencing with other DNA tests, it is important to note that DNA testing based on sequencing technology is much more advanced than DNA tests used by companies like 23andMe and AncestryDNA.

Advantages of
Whole-Genome
Sequencing

Provides a high-resolution, base-by-base view of the genome
Captures both large and small variants that might be missed with targeted approaches
Identifies potential causative variants for further follow-up studies of gene expression and regulation mechanisms
Delivers large volumes of data in a short amount of time to support assembly of novel genomes

An Uncompromised View of the Genome

An
Uncompromised
View of the
Genome

Unlike focused approaches such as exome sequencing or targeted resequencing, which analyze a limited portion of the genome, whole-genome sequencing delivers a comprehensive view of the entire genome. It is ideal for discovery applications, such as identifying causative variants and novel genome assembly.

SZA Longevity Whole-genome sequencing based tests can detect single nucleotide variants, insertions/
deletions, copy number changes, and large structural variants. Due to recent technological innovations, the latest genome sequencers can perform whole-genome sequencing more efficiently than ever. As SZA Longevity, we are commited to use latest technology for out tests and analysis.

What can Whole Genome Sequencing based testing reveal about health?

Whole Genome Sequencing identifies all genetic variation in the genome (e.g. single nucleotide polymorphisms (SNPs), indels, and copy number variations) and it is not limited to single-gene sequencing for specific diseases. For this reason, it is the best DNA test to discover genetic health risks and for diagnosis of genetic conditions. For example, WGS can determine if there is an increased risk of developing diseases like hereditary cancers (e.g. a high risk for breast and ovarian cancer) and genetic predispositions to many other health conditions. It can also uncover carrier status for rare diseases. It enables patients to receive comprehensive genetic counseling and improved medical care that takes the genetic disease into consideration. Furthermore, unlike other DNA tests, Whole Genome Sequencing works equally well for people of all ethnicities (e.g. African, Asian, Caucasian, Ashkenazi Jewish, or Native American). You can bring your Whole Genome Sequencing data to a physician or genetic counselor for various clinical analyses including carrier screening, evaluation of disease risks, and rare disease diagnosis.

For example, WGS can determine if there is an increased risk of developing diseases like hereditary cancers (e.g. a high risk for breast and ovarian cancer) and genetic predispositions to many other health conditions.

It can also uncover carrier status for rare diseases. It enables patients to receive comprehensive genetic counseling and improved medical care that takes the genetic disease into consideration.

Furthermore, unlike other DNA tests, Whole Genome Sequencing works equally well for people of all ethnicities (e.g. African, Asian, Caucasian, Ashkenazi Jewish, or Native American). You can bring your Whole Genome Sequencing data to a physician or genetic counselor for various clinical analyses including carrier screening, evaluation of disease risks, and rare disease diagnosis.

A healthy

future
awaits you.

Whole
Exome
Sequencing

Whole exome sequencing (WES) provides coverage of more than 95% of the exons, (the expressed or the protein-coding regions of the genome), which harbor the majority of the large genetic variants and single nucleotide polymorphisms (SNPs) associated with human disease phenotypes.

1 Of the ~3 billion bases that comprise the human genome, only about 1% is represented by coding sequences.1 By focusing on this most relevant portion of the genome, WES offers researchers the ability to use sequencing and analysis resources more efficiently.

WES strategy starts by narrowing down the details of variants to be studied by filtering against databases such as HapMap, from the approximately 3.5 million SNPs identified in the human genome project. This focus enables a simpler way for discovery and validation of causative genes and common and rare variants.

Exome sequencing has been proven useful in the identification of mutations involved in rare Mendelian diseases.2

Whole exome
sequencing
(WES)
vs Whole
genome
sequencing
(WGS)

Both WGS and WES have their own advantages. Understanding the major differences between them could help in determining which method would work best for a particular research purpose.

WES covers only the expressed regions of the genome while WGS provides coverage for both exons (the expressed sequences) and introns (the intervening sequences)
WES uses enrichment strategies with probes against specific regions of interest while WGS uses a reference genome for alignment of all sequences of the genome
Due to the fact that the whole genome needs to be sequenced, WES is more cost efficient than
WGS

Why
whole
exome sequencing?

Enables comprehensive coverage of exons to target medically relevant genomic regions, including known disease-associated sites and untranslated regions (UTRs)
Increases variant discovery potential, including rare and low-frequency mutations using next generation sequencing (NGS) technology
Eliminates the need to sequence the entire genome, offering a cost-effective alternative to WGS

WES
can be
useful
in
multiple
scenarios

Where the causative gene is known for a particular disease (monogenic) and it needs to be investigated for finding the specific variants
In cases where the causative gene is unknown and it needs to be investigated
In cases where multiple genes are suspected to be involved in a particular disease (polygenic)

How
does WES work?

During library preparation, genomic DNA is fragmented, and targeted regions are captured by hybridization using biotinylated oligonucleotide probes in solution. The captured target sequences are isolated using streptavidin beads, and after washing and elution steps, are used for subsequent amplification and sequencing.

SZA Longevity laboratories uses cutting edge technology platforms and high quality kits such as Illumina products for NGS sample preparation, ranging from sample QC, target enrichment to library quantification that enable the preparation of high-quality DNA libraries, critical for obtaining high-quality whole exome sequencing data.

Shotgun

Metagenomic
Sequencing

Shotgun metagenomic sequencing using next-generation sequencing (NGS) techniques provides a way for researchers to survey all genes in all organisms present in a given complex sample. This method goes beyond bacteria, a limitation of 16S rRNA sequencing, and reveals taxonomic (“Who is there?”) and functional (“what are they doing?”) profiles of microbial communities without the need to culture the microbes in a laboratory,1,2 enabling the study of unculturable microorganisms that are otherwise difficult or impossible to analyze. Using this method, researchers may be able to characterize the entire microbial community and produce draft genomes of individual community members.1,3,4

Highly accurate data

Data accuracy is paramount to uncovering the complexity of the microbial population within a given sample. In certain instances, a single sequencing read is used to identify taxa or specific genes, making data specificity and sensitivity critical when discovering genetic variants in a sample. To deliver the high data accuracy and results required by shotgun metagenomics, in SZA Longevity laboratories we use Illumina sequencing by synthesis (SBS) chemistry, which is used to generate more than 90% of the world’s sequencing data.

For high-powered data analysis, we use in-house developed SZA Longevity Metagenomics analysis pipeline and Illumina DRAGEN (Dynamic Read Analysis for GENomics) Bio- IT Platform which provides accurate, ultra-rapid secondary analysis of NGS data.

Shotgun

metagenomics

vs vs 16S rRNA
sequencing

Metagenomics is different than 16S rRNA sequencing. Metagenomics is the study of the functional genomes within microbial communities.

16S sequencing offers a phylogenetic survey on the diversity of a single ribosomal gene, 16S rRNA, a taxonomic genomic marker limited to bacteria and archaea. While 16S sequencing enables estimation of the relative abundance of these organisms within similar samples, it is not recommended for drawing conclusions across different sample types due to PCR biases and the inability to quantify absolute abundance. For these reasons, research on complex microbial communities is moving from 16S rRNA sequencing to more comprehensive functional representations via shotgun metagenomic sequencing. In SZA Longevity Laboratories, we use shotgun metagenomics to gain insight into microbial community biodiversity and function.

How we
analyze your
microbiome

All the microbial DNA from your stool (in Gut Health Test)/saliva (in Oral Health Test) sample is cut into short fragments. Then we use a high-tech machine that reads the genetic code of a selection of these fragments, giving a snapshot of all the microbial DNA that’s in there.

Once we have the DNA sequences, we move from the laboratory to our computers and get to the most challenging part of the process: figuring out which microbes all the different snippets of DNA belong to.

It’s a bit like taking a famous painting like the Mona Lisa and photocopying it 10,000 times, then chopping it up into thousands of pieces, throwing away 95% of them, putting the remaining pieces in a box, and asking someone to recreate the original picture.

All of this takes time. The process of reading the DNA fragments alone takes around 48 hours. And because every microbiome we analyze is unique, figuring out which microbes are in there takes another 2-3 days.

SZA Longevity laboratories uses cutting edge technology platforms and high-quality kits such as Illumina products for NGS sample preparation, ranging from sample QC, target enrichment to library quantification that enable the preparation of high-quality DNA libraries, critical for obtaining high-quality metagenomic sequencing data.