Longing for Home and Better Outcomes

Longing for Home and Better Outcomes

Poor guy. Since he was little, we knew he had the lungs of a whale. His cries reaffirmed this talent, echoing down the halls. He wants to go home, NOW! Yes, Noodle B. was not enjoying his medical visit. I also knew he would not be a happy camper if he needed another surgery. You see, our elderly furry head-of-the-household does not have the best post-operative experiences. However, I did not know, until recently, that he has that post-op issue in common with many humans.

As we get older, our ability to bounce back quickly from non-emergency surgeries diminishes (Gajdos et al., 2013). This can result in numerous complications and longer stays in the hospital rather than going to recover in the comfort of home. Although chronological age (not our true biological age) might help assess risk for surgery, is there something better?

A research group sought to answer that question by looking at protein changes and post-operative experiences (Fong et al., 2019). From blood samples of people from the Successful Aging after Elective Surgery (SAGES) study, the team looked for changes in protein levels using SomaLogic® technology. After surgeries, the team noted 43% of the proteins analyzed showed significant changes from the pre-operation levels, some of which were not found in other studies. From their analysis, changes in protein levels could potentially be explained by changes in levels of regulating proteins upstream in the cascade of signaling events, such as pro-inflammatory cytokines.

So, did they identify a new way to identify a patient needing more time in the hospital after a surgery or being discharged to a post-acute facility? From the small study, the team did find encouraging – but not definitive – results. One protein in particular, IL-6, showed that its levels prior to surgery could be a good indication that the patient will need more time in the hospital. After surgery, IL-6 and several other proteins appear to offer an early alarm of problems and the need to be discharged to a post-acute facility.

It is encouraging to think that the medical community is on the cusp of having new tests that may help surgeons and other medical care staff better stratify and plan human post-op care. Maybe someday it will even lead to help for Noodle B and his kin.

References
Fong, T. G., Chan, N. Y., Dillon, S. T., Zhou, W., Tripp, B., Ngo, L. H., . . . Libermann, T. A. (2019). Identification of Plasma Proteome Signatures Associated With Surgery Using SOMAscan. Ann Surg. doi:10.1097/SLA.0000000000003283

Gajdos, C., Kile, D., Hawn, M. T., Finlayson, E., Henderson, W. G., & Robinson, T. N. (2013). Advancing age and 30-day adverse outcomes after nonemergent general surgeries. J Am Geriatr Soc, 61(9), 1608-1614. doi:10.1111/jgs.12401

 

What are Proteins? Chopped Liver?

What are Proteins? Chopped Liver?


By Laura Mizoue

You’ve heard of insulin, right? You probably know that it helps regulate blood sugar, that its levels rise and fall depending on what and when you eat, and that a lot of diabetics have to inject themselves with it. But did you know that insulin is a protein?

Proteins have a serious branding problem. Say “protein” and most people think chicken or beef. Say “protein molecule” and it draws a blank stare. This presents a real problem when you’re trying to explain the value of measuring thousands of proteins in a person’s blood. And the maddening part is that most people already know how important insulin, hemoglobin, collagen, growth hormone, liver enzymes, inflammation markers and clotting factors are, they just don’t know that they’re proteins.

Because there are so many different proteins (molecules) in the human body — approximately 20,000 — and they do so many completely different things, proteins are never called proteins. In fact, proteins go by a host of monikers — enzymes, hormones, antibodies, regulators, receptors, transporters, signaling molecules — pretty much anything except the word “protein.”

Of all the names that proteins are called, the one that’s the most misleading is “gene expression product” because it implies that genes are where the action is. But opioids, statins, NSAIDs, SSRIs, ACE inhibitors and almost all other pharmaceutical drugs don’t target genes, they target proteins.

Whenever genomic testing companies want you to “meet your genes” what they really want you to do is meet your proteins. This is because your proteins, not your static pieces of DNA, are the molecules that actually do the work to keep you alive and well. If a mutation in a gene is associated with disease, it’s usually because it results in a defective protein that can’t do its job effectively or a protein that doesn’t even show up to work.

And they’re important jobs: stabilizing your blood sugar, transporting oxygen, helping you move, regulating your mood, fighting infection. Sometimes your body can get by for a while, but over time, if all your protein players aren’t working together in a coordinated fashion, the work situation breaks down and bad things can happen.

At SomaLogic, we measure the levels of approximately 5000 human proteins from a single blood sample. We believe that proteins directly reflect what’s going on in the human body and can help predict what’s going to happen in the future.

So let’s tell it like it is and call a protein a protein.

 

Dynamic Data for a Dynamic You

Dynamic Data for a Dynamic You

Do you know how many different hats you wear in a day? Think about all the different roles you may take on during the course of the day – parent, significant other, boss, employee, cook, cleaner, accountant, household zookeeper, negotiator, etc. The number of roles can seem endless, but they reflect just how “dynamic” you can be and have to be. Like you, life is, indeed, dynamic. Including our health, especially how it changes over time. The question is what data will help – static or dynamic data – in managing your health?

What would static data be? Well, your genetic code that you were born with could count as static for the most part. For those of us growing up in the post-Human-Genome-Project world, it has been drummed into our heads – hyped even – that our genes define us. By examining our DNA (the body’s equivalent to the 0’s and 1’s used to create software, such as genes), we can see what our health future has in store. But what if you are dealt a dreadful set of gene cards? Fortunately, we have learned enough now to know that you are not out of luck: We now know that genes do not dictate fate in the vast majority of cases.

Also, sequencing your genome (all the DNA stuff you inherit) may not accurately describe your complete genetic portrait. You may in fact have more than one genome residing in your body for a variety of reasons which, in addition to just the regular errors associated with DNA sequencing at scale, could compromise the accuracy of any conclusions drawn.

However, even if you had your complete and error-free genetic report in hand, interpreting what it means with regards to health is still uncertain. Turns out that a single mutation (i.e., variation) rarely means you will get “x” disease or condition. In fact, research has shown that variants found in 11,544 genes to be associated with at least one of 518 traits (Watanabe et al., 2019). So, thousands of genes may have influence on a single trait.

Now, let’s examine dynamic data. A wonderful example would be proteomic (all your proteins) data. Proteins are the products of your genes. Yet, how much or little a protein exists can be influenced by so many factors and change throughout the day, etc.

At SomaLogic, we have worked for 20 years to develop the technology to monitor the rise and fall of protein levels and understand how those reflect a tremendous amount of detail about your multi-tasking body and your health. In fact, these fluctuations have generated so much information that hundreds of papers have been written, with many more yet to appear. From the bounty, we see just how protein information might help with arthritis, alert patients about an impending early demise or a non-ideal surgery outcome (Fong et al., 2019), foretell possible failure of a clinical trial (Williams et al., 2018), provide a better alert than traditional “gold standards” regarding a cardiovascular event (Ganz et al., 2016), etc. Protein information could even tell how your body responds to a diet (Thrush et al., 2018) or how exercise is affecting it (Santos-Parker, Santos-Parker, McQueen, Martens, & Seals, 2018).

Let’s get back to our question. What data are as dynamic as you? The answer lies in your proteins. Knowing your protein changes and how to optimize them could help you more effectively meet all the demands of your many different roles.

 

References

Fong, T. G., Chan, N. Y., Dillon, S. T., Zhou, W., Tripp, B., Ngo, L. H., . . . Libermann, T. A. (2019). Identification of Plasma Proteome Signatures Associated With Surgery Using SOMAscan. Ann Surg. doi:10.1097/SLA.0000000000003283

Ganz, P., Heidecker, B., Hveem, K., Jonasson, C., Kato, S., Segal, M. R., . . . Williams, S. A. (2016). Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients With Stable Coronary Heart Disease. JAMA, 315(23), 2532-2541. doi:10.1001/jama.2016.5951

Santos-Parker, J. R., Santos-Parker, K. S., McQueen, M. B., Martens, C. R., & Seals, D. R. (2018). Habitual Aerobic Exercise and Circulating Proteomic Patterns in Healthy Adults: Relation to Indicators of Healthspan. J Appl Physiol (1985). doi:10.1152/japplphysiol.00458.2018

Thrush, A. B., Antoun, G., Nikpay, M., Patten, D. A., DeVlugt, C., Mauger, J. F., . . . Harper, M. E. (2018). Diet-resistant obesity is characterized by a distinct plasma proteomic signature and impaired muscle fiber metabolism. Int J Obes (Lond), 42(3), 353-362. doi:10.1038/ijo.2017.286

Watanabe, K., Stringer, S., Frei, O., Umicevic Mirkov, M., de Leeuw, C., Polderman, T. J. C., . . . Posthuma, D. (2019). A global overview of pleiotropy and genetic architecture in complex traits. Nat Genet. doi:10.1038/s41588-019-0481-0

Williams, S. A., Murthy, A. C., DeLisle, R. K., Hyde, C., Malarstig, A., Ostroff, R., . . . Ganz, P. (2018). Improving Assessment of Drug Safety Through Proteomics: Early Detection and Mechanistic Characterization of the Unforeseen Harmful Effects of Torcetrapib. Circulation, 137(10), 999-1010. doi:10.1161/CIRCULATIONAHA.117.028213

 

Detecting Alzheimer’s Disease Before Being Erased Away

Detecting Alzheimer’s Disease Before Being Erased Away

Another forgetful moment…Keys found in fridge…Was it just due to it being Monday, to a poor night’s sleep or could it be something more alarming? Events such as these can raise the hairs on most people’s necks. If it turns out to be something worse than just sleep-deprivation, such as Alzheimer’s disease (AD), the person and loved ones may be in for rough and expensive ride lasting decades as the afflicted brain – and its memories and functions – is erased.

AD comes in two forms, early-onset or late-onset, and both produce a range of symptoms from mild to severe (NIA, 2019a). At first, the disease may just manifest in ways that only the person or loved ones may notice – repeating questions, getting lost, putting stuff in odd places (e.g., keys in the fridge), etc. As the disease progresses, cognitive ability gets worse. People may no longer recognize loved ones, hallucinate, and have difficulty carrying out everyday tasks. In the most severe form, the disease essentially erases the person mentally and severs the person’s control of their body. Often towards the end, they lose the ability to swallow, leading to pneumonia and death.

What exactly is happening to the brain that could ultimately erase a person? In a nutshell, the brain is shrinking – considerably. The science is not entirely clear about what is exactly happening, but the data suggests two proteins, amyloid and tau, are at the epicenter (NIA, 2019b). Proteins start to form “plaques” and “tangles,” eventually cutting off neurons from one another. Separated, the cells die, which contributes to the shrinkage and erasure.

The shrinkage does not happen instantaneously, but rather over years to decades. Current methods to diagnose AD include spinal taps, MRI or PET imaging, but may not be sensitive enough to catch early stages or to stratify patients in an optimal way to truly benefit clinical trials of promising treatments (Shi et al., 2019).

Looking at changes in our proteins might be another approach worth trying. In a study with the largest sample size known to date surveying the most proteins possible, a team of researchers went looking for new insights (Shi et al., 2019). Although their work is preliminary, proteomics appears to deliver both better understanding the biology and improvement in ways to treat AD. In their study, they identified ten molecular pathways as markedly changed in AD patients, including some already suspected. Furthermore, the inclusion of protein data improved AD vs. non-AD patient sorting over just using genetic information and age.

A test that can screen accurately for AD and do so better than current tests would be a huge step forward for diagnosing the disease, maybe even pre-symptomatically. At that point, the question becomes: If such a test existed, would you take it? The answer depends, in part, on how soon effective treatments can be found. Perhaps using these same findings will get us there faster too.

 

References

National Institute of Aging (NIA) (2019a). What Are the Signs of Alzheimer’s Disease? Retrieved on September 10, 2019 from https://www.nia.nih.gov/health/what-are-signs-alzheimers-disease.

National Institute of Aging (NIA) (2019b). Video: How Alzheimer’s Changes the Brain. Retrieved on September 17, 2019 from https://www.nia.nih.gov/health/video-how-alzheimers-changes-brain?utm_source=ADvideo&utm_medium=web&utm_campaign=rightrail.

Shi, L., Westwood, S., Baird, A. L., Winchester, L., Dobricic, V., Kilpert, F., . . . Nevado-Holgado, A. J. (2019). Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay. Alzheimers Dement. doi:10.1016/j.jalz.2019.06.4951

 

What is Your Most Realistic Portrait?

What is Your Most Realistic Portrait?

Does a photograph provides the most realistic picture of you? It does not. A painting of you represented by thousands of small dots (an art style known as pointillism) would be the most realistic – especially from a health perspective. Why?

Just like pointillism works of art, we can see the outlines of a complete individual from a distance. When we start getting closer and closer and look at a person from a molecular standpoint, we see that a person is made up proteins, DNA, RNA, fat molecules, etc. Getting even closer, it seems that each dot or molecule can tell us a little bit about the subject, but not provide a fuller picture.

An example may illustrate the point (!). Medical tests, such as the one for prostate-specific antigen (PSA), often look at a single protein in the screening for a disease. However, PSA screening can be problematic for some, leading to unnecessary procedures and unnecessary patient/family anxiety. Looking at just a single protein can warp the perception of the current health status of the patient. As in the case of PSA, a step back to look at all the dots (proteins) that make up you could help provide a clearer picture of your health and indicate what directions need to be taken (Webber et al., 2014; Welton et al., 2016).

Why on earth would looking at thousands of proteins simultaneously provide a better picture of your health? Well, it turns out that proteins are involved in pretty much every single function that your body does to keep you alive and grooving to your tunes. Significant numbers of these proteins are dynamic, meaning that their concentration changes in relation to your lifestyle choices and current health status. Looking at how your proteins change with time can indicate your health journey: whether it will be a healthy one or one plagued with horrendous pitfalls.

Sadly, before now the research/medical community could only get small glimpses into your protein portrait. But now we have the ability to see a more complete picture of how the wide range of protein changes are related to the fuller picture of your health and disease. With the ability to look at thousands of proteins at once, our SomaScan® Platform allows us to paint your protein portrait — your current health status and trajectory — across multiple diseases and conditions.

This new technology is just now becoming available in select places, and it will take some time to become more widely accessible. When it does, we believe that each person will benefit from having their portrait done in a way that captures what is most “real” about their health at that moment in a very precise and personal way.

 

References

Webber, J., Stone, T. C., Katilius, E., Smith, B. C., Gordon, B., Mason, M. D., . . . Clayton, A. (2014). Proteomics analysis of cancer exosomes using a novel modified aptamer-based array (SOMAscan) platform. Mol Cell Proteomics, 13(4), 1050-1064. doi:10.1074/mcp.M113.032136

Welton, J. L., Brennan, P., Gurney, M., Webber, J. P., Spary, L. K., Carton, D. G., . . . Clayton, A. (2016). Proteomics analysis of vesicles isolated from plasma and urine of prostate cancer patients using a multiplex, aptamer-based protein array. J Extracell Vesicles, 5, 31209. doi:10.3402/jev.v5.31209

 

Meet Proteo-you to Become a Healthier You

Meet Proteo-you to Become a Healthier You

I would like to introduce you to you, but not the person you see in the mirror. No, I want to introduce you to “proteo-you,” the version of you made up of proteins. Meeting proteo-you could lead to a healthier you.

It is easy to overlook the fact that we are biologically a lot more than the caloric remnants of lemon curd donuts, bone and sinew, and a couple pounds of bacteria. But proteo-you consists of the building blocks, marvelous communicators and battle-ready warriors for your body – all lumped together under the name “proteins.”

Making their way through the Manhattan-like circulatory subway system of you, thousands of your proteins carry on with their business of making you, “you,” such as relaying messages to other proteins or carrying out specific critical chemical tasks (Lin et al., 2008). In the hustle and bustle of your busy infrastructure, it is also likely that other proteins that originated from microbes, or even from your own dying or damaged cells can be found doing their thing for good or bad. Imagine what we could learn about your body if we could tap into and translate the chatter in your subways.

There is so much information to be had from careful listening. Recently we published the largest protein-focused study of its kind, analyzing blood samples from 17,000 participants — almost 85 million different protein measurements (Williams et al., 2019). From these massive data, we have learned how to extract a range of info from a sample that can reveal a person’s current health status such as having a fatty liver, kidney function, percent body fat, lean body mass, amount of abdominal fat and aerobic fitness. We can even determine how the body responds to alcohol consumption, smoking and physical activity – all from the chatter of proteins. Our findings can also sound alarms about the development of type 2 diabetes or having a heart attack in the next few years.

We are not only listening and translating the protein chatter, but also helping people embrace their proteo-selves to become healthier. For example, we recently started a new study with the Leeds Centre for Personalised Medicine and Health. The aim of the project is to determine if being provided with their protein-based real-time health status will help people at risk of type 2 diabetes make adjustments to their lifestyles to prevent the disease onset and enjoy healthier lives.

And far more than just an academic exercise, we have just begun to offer “proteo-you” tests[1] through select healthcare providers, and expect to continue expanding both the number of tests and number of providers in the foreseeable future.

Why not bypass the doctor and make proteo-you guidance directly available to customers? As Roy Smythe, M.D., our CEO says, we absolutely believe in the democratization of medical information, but want first to vet our technology with doctors and then directly provide people with meaningful relevant information. We don’t want to repeat other companies’ mistakes and bypass the medical community from the outset. We also need to make sure we have all the competencies necessary to deliver directly into a consumer market – things like customer service, and mobile interfaces – that will take us some time to build. And last but not least, we want to get the price of our tests into a range that consumers will find reasonable – that’s achievable in the near term, and we’re working out the science needed to do that now.

As more people become comfortable with their proteo-selves, the realization that proteins are the harbingers of our future health status will become more evident. The final question remaining is, what would the chatter arising from your internal hustle and bustle say about you? Curious? Stay in touch.

 

References

Lin, H., Lee, E., Hestir, K., Leo, C., Huang, M., Bosch, E., . . . Williams, L. T. (2008). Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science, 320(5877), 807-811. doi:10.1126/science.1154370

Williams, S. A., Kivimaki, M., Langenberg, C., Hingorani, A. D., Casas, J. P., Bouchard, C., . . . Wareham, N. J. (2019). Plasma protein patterns as comprehensive indicators of health. Nature Medicine. doi:10.1038/s41591-019-0665-2

[1] SomaLogic, Inc. has developed these tests and determined their performance characteristics. The tests have neither been cleared nor approved by the US Food and Drug Administration.