Using machine learning techniques, including support vector machines, this study demonstrates that gene expression signatures can accurately identify subjects with a clinically isolated syndrome who later progress to multiple sclerosis.
Quantitative real-time polymerase chain reaction analysis was used to identify a minimum number of genes of which transcript levels discriminated multiple sclerosis patients from patients with other chronic diseases and from controls.
When we were launching IQuity, I made an intentional effort to talk with people who had been diagnosed with an autoimmune disease. I wanted to know what I couldn’t find out in the lab – like how it feels to learn you have a life-altering, incurable disease.
After all, how you feel about something determines what you do about it. IQuity makes it possible to know quite quickly, and with a high degree of confidence, whether that tingling in your leg is simply because you sat with your legs crossed too long or is an early symptom of multiple sclerosis (MS).
Multiple sclerosis remains a clinical diagnosis that is based on the historical narrative that the patient gives as well as additional studies which include biochemical studies of the spinal fluid, MRI or imaging studies. They form the backbone on which a clinical diagnosis is made today.
IQIsolate measures gene expression patterns in whole blood. Gene expression is the process whereby instructions found in the DNA become a functional product called RNA. Using gold standard approaches widely adopted in the molecular lab industry, expression of a gene can be quantified to determine the extent to which a particular gene is turned on or turned off.
The genes examined have distinct expression levels across healthy subjects and patients with autoimmune and related conditions. However, discernable differences in these expression levels exist in patients with autoimmune disease and related conditions. The IQIsolate algorithms identify these differences and the provider receives a report that allows the provider to confirm a suspected diagnosis.
Changes in DNA have been studied and documented for decades. And while these changes can be used to craft associations with a variety of human conditions including autoimmunity, the presence of changes in DNA, do not necessarily result in the manifestation of disease. RNA is the secondary molecule that our genetic code gives rise to – and this molecule has function. RNA carries out the instructions found in our DNA. Given that the vast majority of our genome is transcribed into RNA, there is a great deal of information communicated in the cells of the human body. IQIsolate harnesses the information found in a portion of this ‘molecular conversation’ by measuring RNAs that exhibit significant changes across multiple disease types including autoimmune and non-autoimmune patient populations.
What does RNA reveal that can't be obtained some other way?
Analysis of the RNA found in blood provides a snapshot of real-time activities taking place in a patient’s immune cells. IQIsolate compares gene expression measurements found in unique patient samples with a database of disease and non-disease samples that have previously been examined. Computational advances in the area of machine learning enable the creation of computer programs capable of accurately classifying patients that do and do not have a specific disease or condition. In autoimmune diseases, like multiple sclerosis, RNA signatures are detectable at the earliest stages of the disease and precede the tissue damage observed using conventional methods. Information from RNA is another tool in the healthcare provider’s toolbox for rapid identification of patients with and without disease.
The provider, or a designated phlebotomist, collects blood into a special tube (PAXgene Tube) that is sent to IQuity’s CLIA-certified laboratory and the sample is processed to isolate RNA. Real-time PCR (RT-PCR), the gold standard for measuring gene activity, is then used to analyze the sample and IQuity’s patent pending algorithm is then applied to determine if the pattern is consistent with the specific disease/condition or not. The lab then delivers a result to the provider in as little as seven days.
IQuity uses Preanaytix PAXgene tubes. The PAXgene Blood RNA System consists of a blood collection tube (PAXgene Blood RNA Tube) and a nucleic acid purification kit (PAXgene Blood RNA Kit). It is intended for the collection, transport, and storage of blood and stabilization of intracellular RNA in a closed tube and subsequent isolation and purification of intracellular RNA from whole blood for RT-PCR used in molecular diagnostic testing.
How were the IsolateMS and IsolateIBS-IBD tests validated?
The Centers for Medicare and Medicaid (CMS) regulates all laboratory testing performed on humans in the US through the Clinical Laboratory Improvements Amendments (CLIA). To be formally validated through CLIA, the test must meet CLIA-established standards related to analytical accuracy, sensitivity and specificity, as well as result reproducibility, and specimen collection stability. Additionally, through academic, scientific rigor, the fundamental science on which the IQIsolate test platform is predicated was validated through several peer-reviewed journal publications and presentations.
How does IQuity arrive at a definitive yes or no answer?
Through more than 10 years of peer-reviewed research at Vanderbilt University Medical Center in Nashville, TN, IQuity scientists have studied thousands of subjects at various stages of disease, as well as healthy subjects. Analyzing the RNA patterns across multiple diseases led to the development of a suite of algorithms, informed through machine learning, which support the analysis of a patient sample. An individual patient’s profile is compared to a robust database of other patient samples obtained through research efforts conducted by IQuity. The current tests deliver an accuracy rate greater than 90 percent.
The result says the tested blood sample has an RNA expression pattern that is (YES) or is not (NO) consistent with that of a patient who has either been diagnosed with a given disease or is a healthy patient.
For any introduction of new diagnostics or therapeutics, the process of securing reimbursement can take years. IQuity’s tests must first be validated in accordance with CLIA standards and then utilized by providers before we can initiate substantive provider discussions and negotiations. The IsolateMS and IsolateIBS-IBD tests will be commercially available in spring/summer of 2017 and the IsolateFibromyalgia early fall.
What are the tests that were developed using the foundational IQIsolate technology?
IQuity’s tests are convenient blood tests that analyze your RNA to help your provider quickly, accurately, and safely assess whether or not you have a specific autoimmune disease in neurology, gastroenterology or rheumatology. Collectively, the tests were developed by analyzing more than 2,500 patient samples which included patients diagnosed with a specific disease or condition, healthy patients, and patients with similar diseases. Each test can be administered at the earliest sign of symptoms, eliminating the uncertainty and waiting game often experienced during the current diagnostic processes.
IsolateMS™ tells your provider if you have a gene expression pattern consistent with multiple sclerosis. The gene expression pattern IsolateMS looks for was established during the research phase of test development. The test is currently being validated in our CLIA-certified laboratory and will be available in summer 2017.
IsolateIBS-IBD™ tells your provider if you have a gene expression pattern consistent with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). If the pattern scores positively for inflammatory bowel disease, IsolateIBS-IBD will further classify the pattern as Crohn’s disease or ulcerative colitis. The expression patterns for IBS and IBD were established during the research phase of test development. The test is currently being validated in our CLIA-certified laboratory will be available in the summer of 2017.
IsolateFibromyalgia™ tells your provider if you have a gene expression pattern consistent with fibromyalgia, and if the result is No, the test will identify if you have rheumatoid arthritis or lupus. This test is still being validated in the research laboratory and will be available in fall of 2017.
Our suite of tests measure gene expression patterns in whole blood. Gene expression is the process whereby instructions found in the DNA become a functional product called RNA (ribonucleic acid). Using gold standard approaches widely adopted in the molecular lab industry, expression of a gene is quantified to determine the extent to which a particular gene is turned on or turned off.
The genes we examine have robust expression levels across healthy subjects and patients with autoimmune and related conditions. These expression levels produce a consistent pattern for each autoimmune disease IQuity has studied. IQuity’s IQIsolate process identifies which pattern your blood most resembles. The IQIsolate algorithms produce a simple Yes or No test result which allows your provider to confirm a suspected diagnosis.
Gene expression is the term used to describe gene activity, or production of RNA. Gene expression occurs throughout a person's life in the cells and tissues of the body. Gene expression can change in response to disease and other conditions. Analysis of gene expression tells you what's happening in your body right now. Some tests incorporate gene expression to help doctors assess a patient's disease status. RNA testing has been successfully used in clinical practice in oncology and cardiology. Our tests are the first to leverage analysis of RNA to help providers diagnose autoimmune and related conditions earlier and with greater than 90% accuracy.
Through more than 10 years of peer-reviewed research at Vanderbilt University Medical Center in Nashville, TN, IQuity scientists have studied thousands of subjects at various stages of disease. Analyzing the RNA patterns across multiple diseases led to the development of a suite of algorithms that are used to examine patient blood samples. IQuity employed machine learning methods (a form of computer analysis in artificial intelligence) to educate the algorithms to identify an individual patient’s profile compared against a robust database of profiles previously established through research efforts conducted by IQuity. The current tests are greater than 90% accurate in identifying the diseases IQuity has examined.
After the test is performed, your doctor will receive a report with your test results. The report provides a Yes or No result. This report along with clinical information obtained by your doctor can help determine the likelihood that you have a specific autoimmune disease or related condition, such as multiple sclerosis, IBS/IBD – Crohn’s or ulcerative colitis, fibromyalgia, rheumatoid arthritis, or lupus. Since the tests are effective at the earliest onset of symptoms, you can get the answers you need to get started on the right treatment sooner. This leads to better long-term outcomes.
Similar to the majority of laboratory tests, your physician must order the test for you. The test requires a blood sample, taken at your physician’s office or through a blood draw obtained at the location of your choosing by a licensed professional. The sample will then be shipped to IQuity’s CLIA-certified laboratory for analysis. Results are sent to your doctor in as little as 7 days. Your doctor will contact you to discuss your test results and help you understand what the information in your test report means.
We are working hard to make sure doctors and other providers are aware of these new tests to ensure you get answers you are looking for as quickly as possible. You can take an active role in your care by downloading a brochure and sharing the test information with your provider. The brochures can be found on the individual, disease-specific patient pages on the website.
IQuity’s tests are priced consistent with others like it and are often less than other diagnostic techniques.
The cost of diagnosis of an autoimmune disease varies by the number of procedures and time to complete them. IQuity’s tests can be used at the earliest onset of symptoms by a provider who suspects the presence of an autoimmune disease, thereby limiting the number of repeated diagnostic tests over time.
Insurance does not currently cover the test, and payment is the responsibility of the patient. IQuity will actively pursue insurance coverage as soon as possible following the tests’ availability for use by providers.
IQuity is committed to providing access to the tests for as many patients as possible. IQuity will offer financial assistance to patients who qualify based on their financial circumstances. In addition, patients willing to participate in IQuity’s ongoing research and clinical studies qualify for a discounted fee, if the study is taking new patients.
When your provider orders the test, you will receive an authorization code that will be used to pay upfront for the test. IQuity’s patient payment portal will accept payment in the form of a credit or debit card. Once the payment is confirmed, the blood draw can occur as planned by you and your provider.