October/November CKD Insider - Genomics & Precision Medicine
In this month’s CKD Insider: New KDIGO guidelines for diabetics with CKD, Rewind of ASN Kidney Week Reimagined, Genomic State of the Art presentations and brief history behind precision medicine, NIH Funded Genomics Projects, and the Fun Tip of the Day!
Management of diabetes in CKD - a comprehensive care plan.
The KDIGO (Kidney Disease Improving Global Outcomes) Group released this month for the first-time clinical guidelines for diabetes management in chronic kidney disease.
The group consisted of a multinational multidisciplinary group of clinicians and included people with type 1 and type 2 diabetes, those with CKD on dialysis and transplant recipients.
The report is broken up into 5 chapters, for the non-clinicians reading this – Chapter 3 & Chapter 5 might be the most useful to you, as they include practical advice and the reasoning behind it. Example figure shown can be found on page 57
KDIGO 2020 Clinical Practice Guideline for Diabetes Management in
Chronic Kidney Disease VOL 98 | ISSUE 4S | OCTOBER 2020
Thank you for making a positive difference in this world! Whether you recognize it or not, you do make a difference!
Thank you also for subscribing to this newsletter! We hope you find the information interesting & valuable!
Fun Tip of the Day!
Family friendly activities that allow you to still get out and feel connected while staying physically apart. Enjoy!
Museum Tours in person or virtual
History walking tours
Outdoor music before it gets cold depending on where you are.
Recap of the American Society of Nephrology (ASN) Kidney Week Reimagined
ASN President: Where we have been and where we are going!
In a strong opening to the conference, ASN’s President Dr. Anupam Agarwal gives a comprehensive overview of the challenges that face the nephrology field and the changes that must be made to make a difference in kidney disease. He calls out 3 focus areas that ASN is working on: Building the nephrology workforce, Advancing diversity, inclusion and equity, and Expanding innovation and collaboration.
Dr. Agarwal’s recognition and acknowledgment of the issues and challenges that have resulted in the limited focus on kidney disease and his long career as a researcher and a nephrologist give me confidence that he is the right person to not only lead the fight but also inspire and empower others to "Take the Lead" as he says to truly make this the Decade of the Kidney.
Let’s make a difference together! If you see an opportunity to help or improve a person’s life with kidney disease, you must TAKE the lead! We all must do our part to help each other.
Please check out the free Kidney Week presentations here
"State of the Art" Human Genome Focused Technology Talks
To help put these talks into context for you read below, learn some fun facts about the human genome, and get a brief history on the key projects that led to the precision medicine of today.
Key research that led to today's Precision Medicine
The Human Genome Project (HGP)
In 1990, the National Institute of Health (NIH) started the collaborative Human Genome Project with the ultimate goal of obtaining the first complete human genome using DNA sequencing technology. The plan was for this to become a resource for a broad range of biomedical studies, including looking for genetic variations that can increase the risk of specific diseases, and identifying genetic mutations frequently seen in cancerous cells. In 2003, The NIH's goal was reached when the first accurate and complete human genome sequence was completed.
Twenty plus years later, and it is clear that the HGP helped propel sequencing technology forward and made the meaningful application of genomics to the practice of medicine a reality we now call Precision Medicine. Precision Medicine is an approach that gives medical professionals the resources they need to find your unique disease risks and the treatments that work best for you. It takes into account an individual’s genes, environment and lifestyle.
Fun fact: Each cell in our body contains a complete bundled genome which is made up of 3.2 billion DNA nucleotides (Read here to learn the basics on the human genome)
Q1- If you unraveled the DNA from one of your cells and stretched it out, how long do you think it would be?
Q2 - How far do you think all of your DNA would stretch? To the moon and back?
Fun fact: 20 years ago, the NIH spent $2.7 Billion dollars overall on the HGP, with about $1B focused on the actual sequencing of the human genome, completing the project in 13 years.
Q3: How much do you think it costs today to sequence one human genome?
Q4: How much time do you think it takes to sequence a human genome today?
Development of Curated Databases
Background for Global Efforts to Curate the Genome Presentation
Cancer research leads the way
For more than 25 years, genomics has influenced cancer risk assessment, diagnosis and treatment, starting from the first gene associated with breast cancer in 1994 (BRCA1). Today oncologists regularly sequence patients tumors and therefore have acquired large amounts of genomic data that initially was not shared across institutions. In 2014, the nonprofit American Association for Cancer Research (AACR) recognized that combining genomic data with the clinical outcome data creates a powerful tool for doctors to practice precision medicine with their patients. Working with 19 of the leading cancer centers in the world and commercial partners, they created Project GENIE (Genomics, Evidence, Neoplasia, Information, Exchange), a publicly accessible international cancer registry of real-world data which integrates clinical grade cancer genomic data with clinical outcome data for tens of thousands of cancer patients internationally in a secure manner. The first set of integrated cancer genomic and clinical outcome data was given to the global community in 2017. A giant endeavor that will create lasting impact and is a good example of what other disease groups can emulate.
Kidney Disease stepping up to the plate
The NIH funded ClinGen (Clinical Genome Resource) and associated ClinVar database, is a free resource that supports the interpretation of genes and variants by defining the clinical relevance of genes and variants for use in precision medicine and research across diseases. The ClinVar database was launched in 2013, and ClinGen-related working groups have been assembled to tackle many of the key challenges to achieving the goals of ClinGen, including the establishment of standard procedures for evaluating genes, variants, genetic disorders, and phenotypes. Reference.
Most recently, the newly formed ClinGen Kidney Clinical Domain Working Group was developed to curate the validity of genes involved in kidney disease. This is an important step towards advancing treatment outcomes for kidney disease. The insights learned have the potential to make a direct difference in you or your family members lives in the future.
Dr. Heidi L. Rehm’s presentation "Global Efforts to Curate the Genome" reviews the details around the various databases in association with ClinGen, which to date has 1423 researchers & clinicians contributing to this ever-enlarging database of information.
Twenty + years of basic research led to a revolutionary technology
Background for Responsible Pathway Forward Presentation
This year, 2020, the Nobel Prize in Chemistry was awarded to Jennifer Doudna and Emmanuelle Charpentier for the CRISPR/Cas9 genetic scissor technology. These 2 women identified and found a way to utilize a natural system used by bacteria to protect themselves from infection by viruses, and created a technology that precisely cuts any piece of DNA at a precisely chosen location in the nucleus of a living cell, which is revolutionary and can be used for everything from eliminating disease to non-health related uses, which leads to the discussion of when and how to use this technology in an ethical manner.
Dr. Dzau discusses ethics in this regard in his presentation: "Human Genome Editing: Responsible Pathway Forward".
Many researchers helped build the path that led them to their discovery, as usually happens in science - you can read the timeline leading up to the CRISPR/Cas9 genetic scissor technology here.
To see a list of the ever growing publications on this technology go here.
Additional large scale NIH funded projects
The National Institutes of Health began the ambitious "All of Us" research project in 2018 with the goal of enrolling at least 1 million people in the world’s most diverse health database. They are now pivoting to focus on COVID-19 by giving researchers access to data from the 350,000 participants so far, including participants' blood and DNA samples and health records which the hope of shedding more light on how the virus affects various communities. As part of the program, the NIH has promised to return research results to all participants in plain language.
Our second genome
As we continually evolve to get greater resolution in this picture we call life, the focus on the human microbiome (the microbes that live on and in our bodies) has been intensifying as the link between health and the microbiome has started to come into focus. Similarly, to what was done with the Human Genome Project, the NIH created the Human Microbiome Project (HMP/iHMP) to help propel this research forward. The overall mission of the HMP is to generate resources to facilitate characterization of the human microbiota to further our understanding of how the microbiome impacts human health and disease.
What you can do to contribute: You can volunteer for curating the ClinGen data, contribute as a disease expert, or share your own personal sequencing data if you are comfortable with this. You can also join the NIH led All of Us and/or HMP research projects as you feel comfortable.
Q5- If you equated the number of genes in the human microbiome to the # of stars in the sky, do you think there would be more or less microbiome associated genes than the stars in the universe?
Question 1 - 6 ft is how many feet long the DNA from one of your cells would be if you uncoiled each strand and placed them end to end. Remember DNA coils into the shape of a double helix, whose sides are complementary. Reference.
Question 2 - Do this for all your DNA, and the resulting strand would be 67 billion miles long—the same as about 150,000 round trips to the Moon. Reference.
Question 3 - The cheapest cost to sequence a whole human genome is $1000, with an expectation to get to $100 in the near term according to illumina Inc., the leading sequencing company. All 3.2 billion nucleotide letters. This only became possible in the last couple of years. Sequencing costs are decreasing so fast, the government tracked chart here isn't up to date completely but shows the dramatic decrease in costs. Reference.
Question 4- A bit of a trick question as there are many different sequencing instruments with various throughput capabilities available, but the fastest you can sequence a human genome is currently about 1-2 days, but expect that to go down to 1 hour in the near future. Reference.
Question 5 - There are more genes in the human microbiome than stars in the observable universe! And we have just scratched the surface in terms of microbiome analyses. Reference.
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