Week 7: Genome Sequencing, Microbiomics, and Personalized Medicine

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Week 7: Learning goals and objectives

In Week 7 you will be learning about the…

  • Role of the human microbiome in the maintenance of health and causation of disease;
  • Reasons why everyone seems to have cancer;
  • Whole genome sequencing: What it can and cannot do;
  • Challenges (and successes) of pharmacogenomics testing given that most major diseases are caused by the interplay of many genes (and variants) and they arise from both environmental and genetic causes;
  • Ethical, legal, and social implications (ELSI) of whole genome sequencing;
  • ELSI issues and social challenges in “personalized genomic medicine (PGM);
  • Cancer Genome Atlas Project (CGAP) and what it aims to do;
  • Pros and Cons of making DNA sequencing available to everyone.

Your objectives are to:

  • Argue for and against the claim that whole DNA sequencing will represent a genuine “paradigm shift” in the practice of health care;
  • Understand the reasons behind the assertion that there is little clinical value in testing for the common SNPs linked to cancer, in general, Note: BRCA1 and BRCA2 genes are rare variants;
  • Explain the reason(s) why you agree/disagree that “although whole genome sequencing will be a diagnostic tool for patients presenting with disruption of a single gene or chromosomal region but less so for those with common diseases;
  • Understand why the vast community of microbes that dwells inside us will play a key role in governing human health

Education about genetics and genomic medicine is not a task only for health professional education. Genomic medicine will touch every life and virtually every profession in the coming generation.

B. Korf, Wayne H. and Sara Crews Finley Professor of Medical Genetics, University of Alabama

Some genetic testing companies look at the 10 million most common differences –DNA variants–between individuals scattered throughout the 3 billion DNA bases on our 23 pairs of chromosomes. For example, if you have the snippet of DNA that gives you the ability to taste a chemical (e.g., phenylthiocarbamide) that makes many vegetables, like Brussels sprouts, taste bitter, you may be a “supertaster” and differ from people who are impervious to bitter taste—people who generally like Brussels sprouts–by a single spelling change in the four-letter genetic alphabet in the bitter taste receptor gene TAS2R38. That is, you might have a “G” where non-tasters have a “C.”

Similarly, a gene variant (Rs9536314) that scientists already knew to be associated with longer life also seems to make people smarter, and may help offset the effects of normal cognitive decline in old age. (See: Smart seniors might have this gene variant)

Equally interesting is the finding that a variant of a single gene, EPAS1, originally derived from an ancient group of humans who lived in Asia about 40,000 years ago, helps protect against a thickening of the blood in 87 percent of contemporary Tibetans living and working at very high altitudes. (See: Gene from extinct species allows Tibetans to live at high altitude)

These differences are known as single nucleotide polymorphisms, or SNPs (pronounced “snips”). The identification of these common differences has, from the early 1990s until very recently, been the main pursuit of genetic research. The idea was not to find out who likes which vegetables, of course, but to find the genetic variants that increase the risk for major diseases, like cancer and diabetes. But the key word here is “common.”

It was thought that the most common differences–these, roughly, 10 million SNPs (1 in every 300 nucleotide base pairs of DNA)–would be at the root of common diseases. (See: Making SNPs Make Sense). That appears to have turned out not to be true. Instead, it seems that the rare differences, which are harder to identify, accessible only by what is termed,” Exome Sequencing,” hold the key to the diseases that strike the broadest number of people. (See: What is Exome Sequencing?)

It is one reason that the information genetic testing companies generate is so incomplete. By way of “Genome Wide Association Studies” and the “1000 Genomes Project” (as discussed in Week 5) genomics researchers have learned which human genetic variations are associated with, say, a higher risk of heart disease but account for only a tiny fraction of the genetic roots of the disease, itself.

In a non-disease example, scientists know at least 50 places in the genome that are significantly associated with height, but they don’t explain more than 5 percent of the variation in height among any two individuals. As a result, a big question remains to be answered: Even if these rare genetic variants are found, will that lead to treatments for the diseases they help to cause?

Consequently, it is likely to be more difficult to develop treatments than originally thought, if only because there seem to be so many more genetic contributors to common diseases. You may, as many people do, volunteer to participate in such research and, in the process, contribute your own personal genome to the effort to understand the reasons why this is so. And you may choose to have your own genome sequenced to glean its fruits as quickly as possible.

Indeed, the 100,000 Genomics England Project (discussed in week #5) has the potential to make a dramatic impact on the ~75,000 participants with cancer or rare diseases who will be receiving a much-needed diagnosis for themselves or their child. (See: 100,000 Genomes: Impacting real lives)

If you were deemed eligible would you participate in the UK project? What reason(s) would you give for signing up/or not signing up to add your genome sequence to thousands of others? Altruism?; importance of the project?; your “duty”; curiosity; informative i.e., uncover your own genetic risk for disease?; To help your children? (See: What you think about the 100,000 Genomes Project)

Whole Genome Sequencing

Full genome sequencing (FGS), also known as “Whole Genome Sequencing,” complete genome sequencing, or entire genome sequencing, is a laboratory process that determines the complete DNA sequence of an organism’s genome at a single time. This entails sequencing all of an organism’s chromosomal DNA as well as DNA contained in the mitochondria, and for plants the chloroplast as well.

Almost any biological sample—even a very small amount of DNA or ancient DNA—can provide the genetic material necessary for full genome sequencing. Such samples may include saliva, epithelial cells, bone marrow, hair (as long as the hair contains a hair follicle), seeds, plant leaves, or anything else that has DNA-containing cells, such as bones 700,000 years old. (See: Your Neanderthal You)

Because the sequence data that is produced is 6-billion base pairs large, genomic data is stored electronically and requires a large amount of computing power and storage capacity to analyze. (See: Google moves into genome data storage and analysis)

Full genome sequencing would have been nearly impossible before the advent of the microprocessor, computers, and an economy based on the manipulation of information (aka, “The Digital Revolution”). (See: Whole genomic sequencing and you)

George Church, Professor of Genetics at Harvard Medical School and Director of the Personal Genome Project providing the world's only open-access information on human Genomic, Environmental & Trait data (GET).

George Church, Professor of Genetics at Harvard Medical School and Director of the Personal Genome Project providing the world’s only open-access information on human Genomic, Environmental & Trait data (GET).

In 2000, President Bill Clinton signaled the completion of the Human Genome Project at a cost in excess of $2 billion. A decade later, the price for any of us to order our own personal genome sequence—a comprehensive map of the 3 billion letters in our DNA—is rapidly and inevitably dropping to about $1,000 at the present time. Dozens of men and women—scientists, entrepreneurs, celebrities, and patients—have already been sequenced, pioneers in a bold new era of personalized genomic medicine identified as, “The Personal Genome Project.”

The future of whole genome sequencing, in general, is attention-getting in the extreme. The “$1,000 genome” has long been considered the tipping point that would open the floodgates to this revolution, and address a number of questions we might be anxious to answer: Do I have gene variants associated with Alzheimer’s or diabetes, heart disease or cancer? Is there a gene for depression, alcoholism or schizophrenia? Can I get tested for it? Which drugs should I consider taking for various diseases, and at what dosage? In the years to come, doctors will likely be able to tackle all of these questions—and many more—by using a computer in their offices to call up your unique genome sequence, which will become as much a part of your medical record as your blood pressure.

Indeed, many experts are advocating that all newborns have a complete genome analysis done so that preventive measures and preemptive medicine can begin early in life. (See: Exome Sequencing: A medical test that may reveal too much?)

How has this astonishing achievement been accomplished? And what will it mean for our lives? Will your privacy be protected? Will you be pressured, by insurance companies or by your employer, to get your genome sequenced? What psychological toll might there be to discovering you are at risk for certain diseases like Alzheimer’s? And will the government or the medical establishment come between you and your genome?

A 2015 study of what patients affected by rare and genetic conditions, both diagnosed and undiagnosed, was conducted by Genetic Alliance UK to seek their views of whole genome sequencing. Three key findings emerged:

1. Patients want the option to receive as much information about their health as possible from genome sequencing;

2. Patients value genetic counseling before and after genome sequencing;

3. Patients welcome the sharing of their genomic data for research purposes.

In the context of such responses, one wonders if whole-genome sequencing should become part of newborn screening, as well? (See: Whole Genome Sequencing and newborn screening)

On another level—and with a $1,000 genome at the ready—imagine what issue will loom when everyone has their genome sequence on a thumb drive. It’s easy to imagine the kind of online matchmaking service that could be uploaded to a server, which then picks out a date or a mate for you: “I’m looking for an XY (or double X) ATTGAAG with good mitochondrial material. Please contact GenomeMate.com.”

Personalized Medicine

Has the revolution arrived? As discussed in the essay on “Genomics and P4 Medicine” (Week 2) the field of genomics is swiftly moving us into the era of personalized medicine, and a whole genome scan is seem as an essential guide to this brave new future. (See: Medicine just for you and Obama to request research funding for treatments tailored to patient’s DNA)

Personalized (individualized) medicine means knowing what works, knowing why it works, knowing who it works for, and putting that knowledge into practice for patients, or, in other words, an approach which includes an individual’s genetic profile to guide decisions made regardless of the prevention, diagnosis, and treatment of disease i.e.,“Medicine based on genomic makeup.” (See: What is personalized medicine?)

At its core, then, is the idea behind personalized medicine is that the understanding of an individual’s genetic profile opens up opportunities to improve treatments and lower costs.

Former Secretary of the U.S.Health and Human Services (HHS), Michael Leavitt, described the impending shift as one toward “mass personalization.” That is, despite the name, personalized (individualized) medicine will not be characterized by the development of individual drugs for individual people, at least in the foreseeable future. Rather, the shift will be from a one-size-fits-all approach to medicine toward treatments and preventive measures tailored to match the genetic profiles of smaller but significant populations.

HHS lists four overarching goals for personalized medicine:

  • Find relationships between genetics and disease that can be put into practice;
  • Prevent insurers or employers from using genetic data to discriminate against individuals with pre-dispositions to disease;
  • Ensure genetic testing is accurate and useful; and
  • Create standards to enable data sharing.

In practice, the hope is that protections to facilitate genetic sharing will encourage individuals to undergo testing, while better data sharing will improve scientific knowledge and speed research breakthroughs. In these ways, personalized health care will help to achieve not only better quality, but also better value in health care.

What is the current state of personalized medicine in the clinical setting?

In the words of Paul Billings, Chief Medical Officer of Omicia: “We’re at a pivotal moment in the history of medicine.” Researchers are jumping on rapid advances in technology to harness this information into medical products, such as diagnostic tests and gene-based drugs (Pharmacogenomics) that enable personalized treatment for a range of diseases.

For example, as discussed in Week 5, Warfarin , a coumadin anticoagulant, is used worldwide for the treatment and prevention of thromboembolic disease. Warfarin therapy, however, can be difficult to manage because of the drug’s narrow therapeutic index and the wide inter-individual variability in patient response.

It is now clear that genetic polymorphisms in genes influencing metabolism (CYP2C9) and pharmacodynamic response (VKORC1) are strongly associated with warfarin responsiveness. Optimal warfarin dosing in turn drives other positive anticoagulation-related outcomes. Therefore, a strong basic science argument is emerging for prospective genotyping of warfarin patients. Effective clinical translation would establish warfarin pharmacogenomics as a heuristic model for personalized medicine.

Kalydeco, a drug that attacks not just the symptoms but the underlying cause of cystic fibrosis, a genetic lung disease that usually kills victims by the time they reach their 40s developed by Vertex Pharmaceuticals, is an excellent example of the promise of personalized medicine.

In addition to its efficacy, Kalydeco represents yet another—and less attractive– face of personalized medicine: it’s cost, which approximates more than $300,000 a year! How are we as a society, going to pay for the small subset of about 2,000 people who have the specific genetic mutation that the drug targets? (See: $300,000 Drug)

In the fast-growing arena of genomics-based drug development aimed at “changing medicine,” the biotechnology company, Regeneron Pharmaceuticals has launched an ambitious effort to sequence DNA from about 100,000 volunteers seeking “low frequency, high impact” genetic variants linked to different diseases that may provide clues to developing new drugs and targeted therapeutics. (See: Aiming to push genomics forward in new study)

As described in Week 5, clinical use of DNA sequencing relies on identifying linkages between diseases and genetic variants or groups of variants. More than 140,000 germline mutations have been submitted to the Human Gene Mutation Database and almost 12,000 single nucleotide polymorphisms have currently been associated with various diseases, including Alzheimer’s and type 2 diabetes, but the majority of associations have not been rigorously confirmed and may play only a minor role in disease. Because of the lack of evidence available for assessing more than 80 million variants identified to date, evaluation bodies have made few recommendations for the use of genetic tests in health care.

Until better evidence becomes available, best practices are needed for making clinical decisions based on genomic information. Identifying these best practices requires understanding how stakeholders gather and evaluate existing genomic evidence to make clinical decisions, develop practice guidelines, and decide whether to cover and reimburse the use of genomic information.

Accordingly, many of the obstacles to achieving personalized health care are basic scientific efforts that need to be conducted if we’re really going to take advantage of this kind of individualized prevention. That list will have to include:

  • Rigorous scientific studies to show that this information can, in fact, be incorporated into medical care in a way that improves outcomes, i.e., that the quantitative risk associated with a particular variant is known;
  • Assessing health behaviors in a way that represents the real world so that it will be possible to get a sense of whether people given this information do, in fact, take full advantage of it and modify their own plans for health maintenance in a way that improves the likelihood of staying healthy;
  • An effective healthcare economics system that allows reimbursement for prevention (and coverage for drug therapy) such that patients are not forced to pay out-of-pocket when, in fact, the system seems willing to pay for them once they fall sick;
  • Prospective studies showing that information about DNA does, in fact, empower physicians to do a better job of prescribing and empowers patients to have a better outcome;
  • Translation of discoveries about the basic molecular underpinnings of disease into truly novel approaches to therapeutics;
  • An effective healthcare economics system that allows reimbursement for prevention such that patients are not forced to pay out-of-pocket when, in fact, the system seems willing to pay for them once they fall sick.

(See: First quick DNA test diagnoses a boy’s illness)

As discussed in Week 5, a wealth of information has emerged from the “Human Genome Project,” the “1000 Genomes Project,” “GWAS,” and “The HapMap Project.”  When the data from these international efforts is added to that which will be produced by “Whole Genome Sequencing” by far the most detailed catalogue of human genetic variation ever known will be possible.

However, In spite of all these impressive advances in gathering information about genomics and its application to public health care in the form of whole genome sequencing, should there be concern that genomic technologies may be surpassing current medical knowledge aimed at the development of effective therapies or ultimately, a cure? What ethical issues might arise in the process, especially when whole genome (or exome) sequencing of newborns, or even early stage embryos, becomes routine? (See: WGS Technology)

For many reasons, then, the question must be posed: Can personalized medicine ever be a reality? If so, when might that be? (See: Obama precision medicine)

Furthermore, consider this~

As the field of genomics garners greater public interest, it is important that the economic impact of advances in the arena are also considered. The idea of personalized medicine, tailored to each individual’s genome, has existed since the inception of the Human Genome Project. As promising as this sort of treatment initially sounds, the economic implications it holds are uncertain at best. Researchers are making advances in the field of genomic research every day, but the vast amount of information remains largely unknown. The human genome, and the molecular controllers that regulate gene expression combine to make an extremely complex map that determines how the human body functions. While the Human Genome Project has been complete for about 12 years, this map will take far longer to unravel in a particularly meaningful way.

This is not to say that viable pharmacogenetic treatments do not yet exist. Many do, and have shown great promise in the certain arenas, such as in the treatment of substance addictions. The issue is that many individuals with the same diseases experience slightly different genetic mutations. In addition, environmental factors are far more constant from person to person in predicting illnesses. Preventative and therapeutic treatments aimed at changing lifestyle and dietary habits appeal to large number of patients, making them inherently more cost effective. Treatments developed under the heading of “personalized medicine” are extremely costly because they cater to very small, specialized markets of individuals. (See: Pharmacogenetics, Pharmcogenomics and Individualized Medicine)

While our knowledge of the genome is ever expanding, it has not yet reached the point where personalized medicine, even with government funding, will be within reach. Research on therapies at our current level of knowledge requires an enormous initial investment of both and time and money, and many attempts do not yield results for years. Developing treatments that target genetic mutations that lead to illness is definitely the future of treatment – but not one that is fiscally attainable for the average patient, most especially if the average patient is not at least minimally “genomics literate.”

Apart, but related to the fiscal issue, is the “genetic literacy” of the general public (current and future “patients”) sufficient to prepare our society for the unprecedented access to our genetic information? The answer is a clear “No!” (See: Genetics and genomics education)

As the current generation of high school students will come of age in an era when personal genetic information is increasingly being applied to health care, it is of vital importance to ensure that this cohort of users understand the genetic concepts necessary to make informed medical decisions. These concepts include not only basic scientific knowledge, but also considerations of the ethical, legal, and social issues that will arise in the age of personal genomics.

This is the overarching goal of this website, and a broad spectrum of other online educational efforts, e.g., the “Personal Genetics Education Project.”

In order to add even more data to the mix, perhaps, everyone should construct a 3-generation family history complete with as much personal health-related and environmental information, as possible to help put disease in a more “genomic context.”

Genomics and Cancer

Environments, both intrinsic (within the body) and extrinsic (outside the body) can ultimately cause cancer. Smoking, irritates and damages the cells of the lung epithelium, and increases the rate of cancer incidence. Prolonged exposure to the sun can lead to skin cancer. Cell division can case spontaneous errors (every third division by a cell line will introduce an error. Recent evidence (as or 2015) concludes that cancer is an inevitable consequence of having populations of dividing cells, and that many cancers are probably not caused by external agents. Nonetheless, pursuing a reduction in exposure to risk factors, like diet and smoking—and cancer treatment when it occurs–plays an important role in reducing the incidence of cancer.

Toward that end, The Cancer Genome Atlas (TCGA) is a project, begun in 2005, to catalogue genetic mutations responsible for cancer using genome sequencing to improve the ability to diagnose, treat, and prevent cancer through a better understanding of the genetic basis of this disease in a long and varied list of tumors in order to give researchers better information and  generate DNA readouts from healthy and diseased cells. (See: The TCGA)

To date, sequencing of cancer cells appears to be the furthest along, likely because cancer is thought to be mostly a disease of DNA. Gene tests are currently available to identify some types of inherited breast cancer, blood cancers like leukemia and lymphoma, and others. Diagnostics in the area of cancer are heavily dependent upon understanding the genome.

Toward that end, cancer tumors are now being classified by their molecular structure rather than the tissue or organ where they are found, such as the breast bladder, or pancreas. A new study finds that approach may lead to more accurate diagnoses and potentially better treatments and outcomes for patients. (See: New way to classify tumors has life saving potential) In this way, cancer can be treated by an increasing number of drugs that block mutations in cancer genes and can halt a tumor’s growth. This new method (labeled as “basket studies”) is at the leading edge of precision medicine that aims to target a particular drug to a specific patient.

As a case-in-point, definitive support for the existence of human cancer stem cells (CSCs)—a type of cancer cell that have the ability to give rise to all the cell types within a tumor—has been found. CSCs are thought to form the ‘root’ of the cancer and are responsible for driving its growth and evolution. (See: Cancer stem cells)

Already, there are tests available to determine in, say, a woman with breast cancer whether or not her tumor is likely to recur, in which case chemotherapy of an adjuvant sort is highly warranted; or whether there’s a very low risk for that, and then chemotherapy could basically be skipped. What effect will the tests have? and Will they change how doctors prescribe drugs and try to influence patient behavior? (See: Fast track attacks on cancer accelerate hopes, Cancer treatment: the second opinion that is saving lives and Personalised cancer vaccines show promise)

Moving rapidly toward achieving that very outcome some cancer clinics in the U.S. are will be offering patients whole-genome sequencing (WGS), the most in-depth and thorough method of mapping tumors at the clinical level for a cost approximating $1,000 per person.

In the words of Kelly Marcom, Duke University cancer researcher, “It will be a while before we know what to do with all that information and how to marry that with the patient’s own genetics and how to use that to refine treatment. But that’s where the field is exploding.”

One outcome from a patient WGS is the identification of mutated variants of a gene called PALB2 all of which can dramatically increase a woman’s risk of breast cancer Women carrying the PALB2 gene have a one in three chance of developing breast cancer by the age of 70; The risk is even higher for women with a family history of beast cancer. (See: Next-generation cancer diagnosis)

But, personalizing cancer treatment with genetic tests can be tricky. (See: Personalizing cancer treatment genetic tests can be tricky)

And speaking of identifying and utilizing the best array of health care options in the complex world of genomics, consider findings from the Human Microbiome Project.

The Human Microbiome Project (HMP)

The human body consists of roughly 1014 cells of which only 1013 are human, the remaining 90% non-human cells (though much smaller and constituting much less mass) are bacteria, which mostly reside in the gastrointestinal tract, although the skin is also covered in microorganisms.

Indeed, the commensal bacteria and fungi that live on and inside us outnumber our own cells 10-to-1, and the viruses that teem inside those cells and ours may add another order of magnitude. (See: The body’s ecosystem and We are our bacteria)

Examination of how these microbes impact human health through their association with the body, for example by influencing metabolism, disease susceptibility and drug response, is key for improving human health and, in the process, adds yet another valuable tool in the quest for personalized medicine.

Genetic analyses of samples from different body regions have revealed the diverse and dynamic communities of microbes that inhabit not just the gut and areas directly exposed to the outside world, but also a multitude of other parts of the body. The HMP aims to characterize the microbial communities found at several different sites on the human body, including nasal passages, oral cavities, skin, gastrointestinal tract, and urogenital tract, and to analyze the role of these microbes in human health and disease. (See: The HMP)

European and Chinese researchers recently catalogued all the microbial genetic material in stool samples they collected from 124 individuals. After DNA sequencing analysis, they published a list of 3.3 million genes!

Advances in whole DNA sequencing technologies have created a new field of research, called “Metagenomics,” allowing comprehensive examination of microbial communities, even those comprised of uncultivable organisms. Instead of examining the genome of an individual bacterial strain that has been grown in a laboratory, the metagenomic approach allows analysis of genetic material derived from complete microbial communities harvested from natural environments (e.g., the “PathoMap Project” to map the bacterial microbiome of New York City) – and around the world!(See: The human gut project)

Together with the Human Microbiome Project, this approach, will complement genetic analyses of known isolated strains, providing unprecedented information about the complexity of human microbial communities.

Many ethical issues arise from the conduct of human microbiome research, in general. These include:

  • the equitable selection of research participants;
  • informed consent and respect for autonomy;
  • data sharing and protection of privacy;
  • invasiveness of sampling and minimization of research risks; and–
  • whether and how research results and incidental findings should be returned to participants.

In addition to these issues associated with the conduct of the research itself, human microbiome research has many broader societal implications. These range from how—

  • the research findings will eventually be applied in both clinical and non-clinical contexts;
  • new products likely to arise from the research (for example, probiotics) will be regulated;
  • this new knowledge will be understood, and used, by the public;

to how—

  • it will potentially alter people’s conceptions of health and disease or even of what it means to be “human.”

In recognition of the importance of these issues, a portion of the HMP budget is being allocated to the support of studies designed to address the ethical, legal, and social implications of human microbiome research. By leveraging both the metagenomic and traditional approach to genomic DNA sequencing, the HMP will lay the foundation for further studies of human-associated microbial communities and their role in health and disease.

In that regard, an international effort is currently underway to catalogue thousands of new microbe species by gathering their DNA sequences in an effort to find new links between the microbiome and human health thereby providing public health professionals new ways to fight disease. (See: The IHMC)

Now that pathogen genomes can be completed in less than a day, the time is right to begin using them to control and treat serious infections, at least in the developed world. This will take two developments:

  • The introduction of sequencing into local diagnostic laboratories; and
  • The creation of automated tools to interpret newly sequenced genomes

(See: Health care bring microbial sequencing to hospitals)

Resources and Discussion

Questions for Discussion

  • What do you see as some of the most likely (positive and negative) ethical and legal outcomes from whole genome sequencing in both adults and newborn children?
  • Do you believe that people should be able to have free access to their genetic profiles, or should they be available only through physicians?  Why/Why not?
  •  In medical practice, an incidentaloma is a test result that a physician wasn’t looking for, like finding a cancerous tumor on an X ray of a broken bone.  Discuss how personal genome sequencing could provide “too much information” in the form of incidentalomas.
  • Name a gene variant that you would want to know is in your genome, one that you wouldn’t, and one that you consider to be frivolous.
  • Explain why the bioinformatics of cataloguing the human microbiome is much more complex than sequencing a human genome.
  • Discuss how an old tool such as a pedigree is still useful in interpreting whole-genome or exome sequences.
  • Explain why cancer is usually a genetic disease at the molecular and cellular level, but not at the whole-body level.
  • Why is knowledge gained from HMP research is described as a “valuable tool in the quest for personalized medicine”? 
  • What is the difference (if any) between the aims of the (microbial) “PathMap” and the (human) “HapMap” projects?