By Deborah Borfitz
September 15, 2022 | The greater New York metropolitan area is the epicenter of an ambitious human genome sequencing research project newly launched by Mount Sinai Health System and the Icahn School of Medicine at Mount Sinai in collaboration with the Regeneron Genetics Center (part of biotechnology company Regeneron). If the vision is realized, Mount Sinai will enroll a million patients into a study over the next five years that will sequence and analyze the DNA in their blood to tease out the role of genetics and environment on health, according to Alexander W. Charney, M.D., Ph.D., associate professor of psychiatry, and genetics and genomic sciences, as well as leader of the Mount Sinai Million Health Discoveries Program.
“Genetics is moving us into the future where every treatment is data-driven for a given patient,” says Charney, who is also director of The Charles Bronfman Institute for Personalized Medicine at Icahn Mount Sinai. Researchers already have a sizeable dataset available from Mount Sinai’s BioMe Biobank—a growing repository containing genomic information on tens of thousands of patients across the five boroughs of New York City—which Charney most recently tapped to find rare patient-specific genetic subtypes of schizophrenia.
But that’s still not enough data to confidently answer basic questions like whether genetics can help predict treatment outcomes, he notes. To solve those puzzles, mathematical models require an extremely large dataset to account for the multitude of variables that might explain a result.
In contrast to NIH’s All of Us program, the Mount Sinai initiative aims to recruit participants from within its existing patient pool. It’s a funding challenge. In academic medicine, it is not financially feasible to sequence the genomes of a million people using traditional mechanisms such as philanthropy and government grants, continues Charney. The Regeneron Genetics Center, on the other hand, had the will and wherewithal. The company is physically close to Mount Sinai, academically oriented, and has a proven track record of doing the sequencing work at scale and partnering with academic institutions.
The big challenge now is to execute on the vision, which includes overcoming logistical hurdles such as electronic systems that don’t talk to each other, educating busy clinicians and uninformed patients of the value of their participation, and simplifying the enrollment process, Charney says. All the information needed for the study is fortunately already embedded in the electronic health record (EHR), which effectively shortens the interview process with patients and should enhance their chances of enrolling.
“It is really an all-hands-on-deck situation,” he says of the study. “We want everyone who works in the Mount Sinai Health System to say this is something they are part of... and [see that] it’s worth doing.”
Co-leaders of the genome sequencing research project are Girish N. Nadkarni, M.D., Dara Meyer, and Rachelle Weisman, all at Icahn Mount Sinai. Nadkarni is also, along with Charney, the director of the Institute for Personalized Medicine, which is administering the Mount Sinai Million Health Discoveries Program.
The enrollment conundrum has been encountered in other studies conducted at Mount Sinai involving biospecimen collection from many human subjects, says Charney. He draws from personal experience on two particularly challenging studies. The first, the Living Brain Project, began a decade ago where researchers wanted to obtain samples from the brain of living people. What is known about the brain is based entirely on what could be learned from organs donated after death which, he says, is problematic because at the biological level brains after life are unlikely to be the same as those during life.
To test that theory, Charney and his colleagues did the seemingly impossible with a simple but creative solution: place a research coordinator next to neurosurgeons already planning to remove a bit of healthy brain tissue from patients for various clinical care purposes. Instead of throwing the healthy brain tissue in the garbage, the samples are conserved for research purposes, he explains.
Other than obtaining consent, neither the physician nor the patient has to do anything different. Mount Sinai consequently grew—and continues to grow—the biggest collection of brain tissue from living people in the world, says Charney.
Similarly, for 48 days early in the COVID pandemic, Mount Sinai investigators succeeded in enrolling patients into a study who had recently come in for a blood draw by storing those samples in a freezer and approaching them later for consent rather than while they were masked, sick, and terrified within hospitals under siege by the unknown virus (including at a tent hospital in the park), Charney says. This sensible approach resulted in 90% of patients agreeing to participation.
Charney says he believes that getting to the one-million goalpost with the new sequencing research project will also happen simply by thinking through the potential barriers. Every year, 300,000 individuals in the health system are getting their blood drawn for clinical purposes and, if those tubes were stored, the research team could theoretically get consent from most of them. How to best go about doing that is not a settled issue.
The more immediate challenge will be setting up an interoperable system for tracking blood samples, which will be collected at eight different hospitals and dozens of outpatient clinics comprising the Mount Sinai Health System but be sent via a courier service to one central storage location. Charney and his team need to create new systems to report when tubes of leftover blood are sent to the central lab and to know which freezers house which samples.
All those electronic systems will need to connect and communicate in a coordinated, effortless way, he says. Existing systems will need to be modified to enable the information exchange.
Roles And Responsibilities
Regeneron’s role with the Mount Sinai Million Health Discoveries Program is the same as it was for the BioMe Biobank—to do the exome sequencing, whole-genome genotyping on all the DNA samples, and whole-genome sequencing on a subset of those samples, Charney says. Mount Sinai is contracting with Vibrent Health, the technology platform for the National Institutes of Health’s million-person All of Us Research Program, to handle e-consenting, data collection, and participant engagement.
Vibrent’s user-friendly platform allows people to consent using a digital device, a streamlined approach consistent with studies at this scale, he continues. In lieu of reading through a huge packet of printed information in front of a research coordinator, individuals will be able to watch a video that summarizes the study and highlights the most important points. They’re then able to go through the consent form at their leisure and answer a few questions to verify their comprehension before choosing to enroll or not.
Beyond enrolling study participants, Mount Sinai will provide deidentified data on those patients from the EHR system. The EHR will be used in a few different ways, says Charney, including to understand who has had blood drawn and where those patients were being treated to guide recruitment efforts.
It will also be used to create a deidentified dataset—a limited set of patient information, like medications prescribed or diagnoses given, scrubbed of anything that might make people knowable—which researchers in and outside Mount Sinai might analyze along with the companion genetic data to get insights into the genetic basis for disease, Charney says. Researchers at Mount Sinai may additionally want the genetic data to be tied back to other patient information that isn’t captured in the EHR, such as imaging tests and EKGs.
Only the more limited deidentified dataset will be broadly available to other academic institutions, he adds. The particulars of the external data-sharing process haven’t yet been established.
The research team is taking a multifaceted approach to patient recruitment for the Mount Sinai Million Health Discoveries Program, Charney says, emphasizing that the focus is on informing people who are getting treatment at Mount Sinai anyway versus a citywide enrollment campaign. “This is a study on the patients we treat... so it is really a matter of engagement within our health system.”
An app specific to Mount Sinai will be used to interface with healthcare providers and spread awareness and information about the study, he continues. Outreach efforts will be sweeping and touch everyone, including doctors, nurses, social workers, patient care associates, and other staff and faculty throughout the Mount Sinai Health System as well as patients directly. “That’s how we’ll make sure patients coming to Mount Sinai will have heard about the study and be given the basics and then the opportunity to choose to participate or not through the informed consent process.”
Clinician engagement has been both an opportunity and a barrier, Charney says. Physicians, for example, are “always spread too thin” and recruiting patients into a study will at times fall to the bottom of their priority list.
Likewise, phlebotomists are probably not interested in the inconvenience—to themselves as well as patients—of doing additional blood draws for a study, he continues. Taking that piece out so they’re not doing anything extra for research purposes makes them feel considered and thus more interested in participating.
Discovery To ‘Last Mile’
To appreciate the potential of one million sequenced human genomes, Charney points to scientific discoveries already made with the more limited BioMe dataset. He and his colleagues used it for a study of schizophrenia, for example, to look at 10 genes recently identified to harbor higher rates of rare damaging genetic variants in individuals with the disease compared to healthy controls (Nature, DOI: 10.1038/s41586-022-04556-w).
The new investigation looked at 30,000 patients in BioMe to identify individuals with these types of rare damaging genetic variants in the 10 genes. One person they identified didn’t have any severe mental illness, but schizophrenia affected four siblings and across many generations schizophrenia as well as intellectual disability was reported. With the family’s partnership, further studies might now be done to explore the suspected genetic cause and potential treatments of the disease in the affected family members.
Cancer researchers at Mount Sinai seem particularly enthusiastic about the Million Health Discoveries Program, says Charney. They view it as “an amazing resource for understanding how cancer occurs” by allowing a comparison of the regular genome of the patients they treat with information gleamed from the tumors they later develop.
Making sense of all the big data being generated by the Mount Sinai Million Health Discoveries Program requires multi-modal data science looking at genetics in the context of all the different levels of biology (proteins, RNA, lipids, and metabolites) that are “interacting in ways we don’t quite understand,” as well as data contained in the EHR, Charney says. “More data does not mean answers... we need tools to parse information out of all this data.”
The “last mile” in this discovery journey will be to rigorously test new treatments and interventions before they are incorporated into clinical care, he notes. Data and statistical techniques can be used to make sound predictions about health outcomes, which can then be built into the interface that clinicians use as they’re treating patients. But too often this has been done without first pragmatically testing whether the information is in fact helpful, or just creates more confusion among clinicians and patients in the real world.
The HGP benefited biology and medicine by creating a sequence of the human genome; sequencing model organisms; developing high-throughput sequencing technologies; and examining the ethical and social issues implicit in such technologies.What is the top genome sequencing companies? ›
Top 5 Genome Sequencing Companies by Revenue
- Illumina. ...
- Thermo Fisher Scientific. ...
- Agilent Technologies. ...
- QIAGEN. ...
- BGI Genomics.
- •Allows doctors to closely analyze a patient's genes for mutations and health indicators.
- •Can detect intellectual disabilities and developmental delays.
- •WGS is currently available at Yale for patients in the NICU and PICU.
- •Involves Genetics.
The Oxford Nanopore DNA sequencing method can read even more—up to 1 million DNA letters at a time—with modest accuracy. Both were used to generate the complete human genome sequence. In total, the new project added nearly 200 million letters of the genetic code.What are the main aim of Human Genome Project? ›
This ambitious project began in 1990 and concluded in 2003. One goal of the project was to accurately sequence the 3 billion nucleotide base pairs in the human genome. A second goal was to map and identify all of the human genes present in the DNA sequence.What was the result of the Human Genome Project? ›
The project showed that humans have 99.9% identical genomes, and it set the stage for developing a catalog of human genes and beginning to understand the complex choreography involved in gene expression.What company makes the microchip for Imperium? ›
IPGGF - Imperium Technology Group Limited.What company is the king of genome sequencing? ›
Illumina is improving human health by unlocking the power of the genome. Our focus on innovation has established us as the global leader in DNA sequencing and array-based technologies, serving customers in the research, clinical, and applied markets.
Evonetix Granted Patent for Technology Enabling Thermally-Controlled DNA Synthesis.Why is genetic sequencing important? ›
The sequence tells scientists the kind of genetic information that is carried in a particular DNA segment. For example, scientists can use sequence information to determine which stretches of DNA contain genes and which stretches carry regulatory instructions, turning genes on or off.
Genomics has the potential to make genetic diagnosis of disease a more efficient and cost-effective process, by reducing genetic testing to a single analysis, which then informs individuals throughout life.How does genetic sequencing work? ›
Electrodes are placed at either end of the gel and an electrical current is applied, causing the DNA molecules to move through the gel. Smaller molecules move through the gel more rapidly, so the DNA molecules become separated into different bands according to their size.Who sequenced the human genome first? ›
Sequencing Human Genome: the Contributions of Francis Collins and Craig Venter. How did it become possible to sequence the 3 billion base pairs in the human genome? More than a quarter of a century's worth of work from hundreds of scientists made such projects possible.How much of the human genome has been sequenced? ›
Specifically, it accounted for 92% of the human genome and less than 400 gaps; it was also more accurate. On March 31, 2022, the Telomere-to-Telomere (T2T) consortium announced that had filled in the remaining gaps and produced the first truly complete human genome sequence.How many peoples genomes have been sequenced? ›
Today, about 30 million people have had their genomes sequenced.Which of the following was not a goal of Human Genome Project? ›
It does not eliminate all the diseases, but provide us with a way to cope with them.Who participated in the human genome project? ›
In total, the 'International Human Genome Sequencing Consortium', as the Human Genome Project team” was known, involved scientists from 20 institutions in six countries: France, Germany, Japan, China, the UK and the USA (the full list can be found below).When was the human genome fully sequenced? ›
In 2003, the Human Genome Project ended with the generation of an essentially complete sequence of the human genome. The project took the practical approach of using the best-available technologies for sequencing DNA and pushing them to their absolute limits.Was the human genome project successful? ›
The project was an overwhelming success, delivering the first rough draft human genome sequence in 2000 and the final high-quality version in 2003 — ahead of schedule and under budget. on the economic impact of the Human Genome Project.What is a key finding from the Human Genome Project quizlet? ›
A key finding from the Human Genome Project is: Approximately 20,000 to 25,000 genes make up the genome. Approximately 20,500 genes make up the human genome, only twice as many as make up the genomes of roundworms and flies. Human beings are 99.9% identical at the DNA level.
When the Human Genome Project was proposed, the technology to complete it did not exist. One of the major challenges facing scientists was developing the tools that would allow them to achieve their goals.How will the Human Genome Project be useful in developing gene therapies? ›
Answer and Explanation: The Human Genome Project mapped out all the genes of the human genome. Once the loci of the genes were identified, this enabled researchers to identify variations in the genes, leading to potential for gene therapy by removing undesired genes and inserting the desired ones.What is the impact of genomics on the future of healthcare? ›
Genomics has the potential to make genetic diagnosis of disease a more efficient and cost-effective process, by reducing genetic testing to a single analysis, which then informs individuals throughout life.How can the Human Genome Project assist in public health? ›
Sequencing of pathogens, for example, can allow rapid diagnosis and control of disease. To understand the host response to pathogens and the association of genetic variants with susceptibility or resistance to disease, human genomics research is of great value.How does sequencing a person's genome influence their medical treatments? ›
A huge breakthrough in medicine has been the ability to sequence the DNA in cancer cells. The sequence can be compared to the sequence found by the Human Genome Project. This allows scientists to work out which genes are mutated and this gives them ideas for developing medicines.Is Human Genome Project successful? ›
On April 14, 2003, the International Human Genome Sequencing Consortium announces the successful completion of the Human Genome Project.What are the overall benefits consequences of the human genome project and the ability to quickly perform DNA sequencing? ›
The benefits in this field could include better diagnosis of disease, early detection of certain diseases, and gene therapy and control systems for drugs (1). In the future there should be new treatments in molecular medicine that don't treat the symptoms but look at the causes of the problem at hand.In what ways do you think information from the human genome project can affect your lives? ›
- Improved diagnosis of disease.
- Earlier detection of genetic predispositions to disease.
- Rational drug design.
- Gene therapy and control systems for drugs.
- Pharmacogenomics "custom drugs"
The primary purpose of sequencing one's genome is to obtain information of medical value for future care. Genomic sequencing can provide information on genetic variants that can lead to disease or can increase the risk of disease development, even in asymptomatic people.How genetics can improve care and health outcomes? ›
One of the most exciting benefits of genomics and precision medicine is the promise of therapies that are tailored to meet each patient's specific needs. Providers can access an individual's genetic code and better determine what sort of treatment is right for him or her, leading to better outcomes and lower costs.
Many diseases, including cancers, are caused by alterations in our genes. Genomics can identify these alterations and search for them using an ever-growing number of genetic tests, many available online.What are the advantages and disadvantages of Human Genome Project? ›
The Human Genome Project is beneficial for science and preventing disease and curing diseases. However, it raises ethical issues as it can cause discrimination by employers and insurers.How can genome sequencing be used to prevent disease? ›
“By analyzing people's DNA, we can discover specific gene variants that may predispose them to specific conditions, or make it more or less likely that they will respond to a specific treatment,” explains Guna Rajagopal, Ph.Why is it important for public health professionals to know about genetics? ›
Risks for almost all human diseases result from the interactions between inherited gene variants and environmental factors, including chemical, physical, and infectious agents and behavioral or nutritional factors, raising the possibility of targeting disease prevention and health promotion efforts to individuals at ...How might the sequencing of the human genome impact on our lives our medical decisions and society? ›
Genome sequencing is being used in medicine to diagnose inherited diseases, target cancer treatments, and identify health risks. Certain variants can increase a person's risk of diseases like cancer and heart conditions.How long does genetic sequencing take? ›
A new ultra-rapid genome sequencing approach developed by Stanford Medicine scientists and their collaborators was used to diagnose rare genetic diseases in an average of eight hours — a feat that's nearly unheard of in standard clinical care.What role does DNA sequencing play in medical research? ›
DNA sequencing is the process used to determine the order of nucleotides in a specific DNA molecule. This information is useful for researchers in understanding the type of genetic information that is carried in the DNA, which may affect its function in the body.