Proteins are the work horses of the human body and its cells, determining both structure and function. The key to discovering a cure for MS may lie in studying the components of proteins and how they interact. Omics research is an emerging field that aims to do just this. The ACP Repository is a growing, vital resource for these studies.
Gene Expression
Amino acids, the building blocks of proteins, are made through a 2-step process. First, a cell’s genetic instructions (DNA) are transcribed into a temporary molecule called messenger RNA (mRNA). Next, this mRNA is translated into a sequence of amino acids.
The genome is identical in every cell, but each cell transcribes different sections of it based on its cell type. This pattern of gene expression (which genes a cell transcribes) determines the cell’s function. During disease, these patterns can change. Studying these changes can provide valuable insights into the biological pathways specific to cells and tissues and how they contribute to disease.
The goal of omics sciences is to identify, describe, and measure all of the molecules that contribute to the form and function of cells, and to understand how they relate to human diseases.
Branches of Omics Research
The ACP Repository is an open-access resource containing blood samples and data from over 3,200 participants. Each sample is accompanied by about 50 pages of self-reported personal, health, and clinical information, collected on a questionnaire, or case report form (CRF).
Researchers using ACP samples and data must return their research results to the Repository database, for sharing with other researchers and benefiting the entire research community. As we distribute ACP biosamples globally and receive those findings back, the database grows with genomic, transcriptomic, and proteomic datasets. When the same samples are studied by multiple teams, overlapping datasets with different types of information are created. These datasets enable “virtual collaborations,” where researchers can use others’ results to inform their own work or conduct additional analyses. This feature makes the ACP Repository a vital resource for MS research. ACP is cataloging and combining these datasets to inspire new collaborations and advance MS research.
By studying regulatory RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), scientists can better understand how genes interact and how the products of gene activity control various biological functions.
Our genes are like instruction manuals for our bodies. Only about 2% of our genetic material contains instructions for making messenger RNA (mRNA). This mRNA directly tells our cells how to make proteins, which are important building blocks in our body. The other 98% of our genetic material includes instructions for making different types of RNA, including regulatory RNAs. These regulatory RNAs don’t tell the body how to make proteins directly. Instead, they act like control switches for our genes. Regulatory RNAs help decide which genes should be active or inactive at any given time. They work alongside mRNAs in this process. While mRNAs act as couriers, carrying genetic instructions for protein production.
Biomarkers are what’s left behind during the processes described above. Using samples and data from the ACP Repository, leading researchers are uncovering new protein and RNA biomarkers for MS. Discover the latest breakthroughs with us below!
Using ACP Repository samples, Octave Bioscience applied a quantitative proteomics approach to identify 20 proteins whose expression levels are linked to increased disease activity in MS. A panel of these proteins is now being used in Octave’s Multiple Sclerosis Disease Activity (MSDA) test. MSDA has been implemented in many leading MS centers across the United States
“By providing a more comprehensive picture of disease activity, Octave’s Precision Care solution and its MSDA test can empower those living with MS and their healthcare providers to make more informed decisions about their care. We are thrilled that our Repository samples and data have enabled this research.” – Sara Loud
Investigators at Regulus Therapeutics used Repository samples to conduct a pilot quantitative transcriptome study to determine the feasibility of a blood test for diagnosing MS using regulatory miRNA biomarkers. This research compared expression levels of miRNAs in MS patients with those in people with similar diseases that are often mistaken for MS with the goal of developing a panel of miRNAs that accurately predict MS in patients with unclear symptoms. These valuable data have been returned to the Repository database for the benefit of future studies.
“If we’re to get better treatment to patients, we must move the field forward and find these markers that better explain why people’s experiences of MS are so different. That can help us better predict who is going to have more aggressive disease, even to be able to measure if a treatment is working before new lesions show up on MRI. These are all of the things that biomarkers do. They help us tailor treatment.” – Stephanie Buxhoeveden
As part of her doctoral dissertation, Stephanie Buxhoeveden and her colleagues at Virginia Commonwealth University School of Nursing studied the epigenetic basis (how environmental factors can influence gene activity without changing the DNA sequence) for how differently MS presents in males and females.
In Stephanie’s words, “Genetics are your DNA, it never changes, but MS is more of an epigenetic disease. Epigenetics have the ability to alter how our genome is expressed. Things like viruses, environmental exposure, and hormones can actually cause a mismatch between the DNA that’s in your body and what the RNA reads and expresses.” The research team used a new method called RNA sequencing (RNA seq) to study RNAs. This method provides detailed information about RNA structures and can be used in AI analyses to understand how these structures affect RNA function.
Males and females have clear differences in how likely they are to get MS and how severe their symptoms become.
They found distinct epigenetic pathways (mRNA and miRNA expression) in females that cause excessive inflammation, while males had higher expression of pathways that cause more catastrophic neurological degeneration, cognitive decline, and physical disability. They also found protective pathways in females, potentially explaining why their MS tends to be less severe. This research offers important insights into the biological mechanisms underlying sex differences in MS progression, advancing our understanding of the disease and paving the way for future research in this area.
“I have such a deep gratitude to the patient pioneers who gave the samples for my study. It’s so amazing to think in 2006 somebody donated their blood to the ACP Repository, hoping that one day science and researchers would come so far that they could do something really meaningful with it. In a similar way, it’s the most touching, humbling thing that people show up to the iConquerMS network, selflessly donating their data, their time, their rich experience. They are the heart of everything we’ve done.” – Stephanie Buxhoeveden
The research team at Decode Health aims to develop new blood tests to help doctors diagnose MS early using RNAseq. They have identified unique lncRNA biomarkers in the blood of people with different types of MS from the ACP Repository. These tools will aid in early diagnosis, allowing for timely and effective treatment, and help differentiate between the forms of MS using gene expression.
Repository 2.0 – Where do we go from here?
A new collection of blood samples from iConquerMS members would not only refresh the ACP Repository’s inventory but also include samples from individuals who have taken newer MS treatments. These samples could then be analyzed using advanced ‘omics methods, including RNAseq. In addition, collecting blood samples and accompanying data over time would provide a detailed picture of each participant’s MS journey.
The people who contributed samples and data to the ACP Repository (perhaps you are one of them!) knew that they were helping researchers conduct studies into the causes, mechanisms, and treatment of MS and other diseases. What they (you) might not have known is that they (you) were adding to what has since become the largest and most diverse collection of data about MS in the world. There is no other dataset that combines biosample analyses with personal and clinical data that can rival what we have built together. Moving forward with a prospective collection of samples and data from iConquerMS participants would further enrich this powerful resource. Its potential to uncover the underlying causes of MS, as well as new diagnostics, treatments, and cures, is unparalleled!
