An international study has shown that analyzing about 1,500 proteins in the blood - in conjunction with genetic data - can help uncover the potential causes of rare diseases that genome sequencing alone could not diagnose, by clarifying uncertain genetic changes and identifying candidate genes that may be responsible for the disease.
Researchers from Queen Mary University of London, the Berlin Institute of Health at Charité Hospital, and the Genomics England Foundation participated in the study, which was published in the journal Science Translational Medicine on September 9, 2026. They analyzed blood samples from people who remained without a genetic diagnosis after undergoing tests within the “100,000 Genomes” project. The results indicate that combining proteomics with genetic analysis may provide an additional tool to improve the diagnosis of rare diseases and detect conditions that are difficult to explain based on genetic information alone.
When genetic tests fail to provide answers
Genome and exome sequencing have transformed the diagnosis of rare diseases, but many patients still have difficulty understanding the underlying causes of their health conditions. Among the most prominent challenges are genetic changes known as variants of uncertain significance (VUS).
These variants are discovered during genetic tests, but scientists do not yet have enough evidence to determine whether they are responsible for the patient's disease.
Blood proteins provide an additional source of information
Blood proteins may provide an additional source of information, as they reflect the biological processes occurring within the body. Unusually high or low levels of certain proteins can indicate that a genetic change affects the function of a gene.
Combining protein measurements with genetic data may provide an additional layer of evidence for understanding genetic variants, said Dr. Giulia Carrasco-Zanini of the Precision Healthcare Research Institute at Queen Mary University of London, first author of the study.
Rather than simply looking for additional genetic changes, this approach can help researchers interpret the genetic information that is already available.
Protein signals to explain ambiguous situations
The research showed that combining genetic data with protein measurements was particularly useful in some patients with hereditary hemorrhagic telangiectasia (HHT), a rare genetic disorder that affects the blood vessels. This approach helped solve cases that remained undiagnosed after genetic analysis.
Protein measurements have also contributed to identifying genetic changes that may not have been captured by traditional methods used to analyze genome sequencing data. The researchers also investigated whether unusual protein levels could be used to detect genes that have not yet been conclusively proven to cause specific rare diseases.
One example is the TIE1 gene, which plays a role in blood vessel function. Scientists have identified a rare genetic variant in this gene in a patient suffering from an unexplained genetic heart disorder, along with exceptionally low levels of the TIE1 protein in his blood.
The researchers found the same genetic variant in the father of the patient who suffered from the same condition, while it was not discovered in the other participants in the “100,000 Genomes” project. Additional laboratory experiments using cells taken from the patient also showed a significant reduction in TIE1 protein levels and signaling, providing additional support for the possible relationship.
However, the researchers stressed that this result represents a candidate association between the gene and the disease, and does not confirm that the TIE1 gene is the direct cause of the condition. Additional evidence is still needed to prove this relationship.
A less intrusive source of biological information
One potential advantage of this approach is that it relies on blood samples, which may provide a more accessible alternative to some laboratory methods that require skin biopsies and culturing cells taken from patients.
Professor Damian Smedley from the William Harvey Research Institute at Queen Mary University of London - one of the study's co-authors - said that protein measurements may help researchers identify genetic changes most likely to affect a patient's health, and direct more focused research.
But this approach faces important limitations. Current techniques measure only a portion of the proteins encoded by the human genome, and some disease-related proteins cannot be reliably detected in the blood.
In addition, not all disease-causing genetic variants change the levels of proteins in the bloodstream. Therefore, this technology cannot yet provide answers for all patients suffering from undiagnosed rare diseases.
Towards a more comprehensive diagnosis
The researchers believe that developments in the field of protein science known as proteomics may make this approach more useful when combined with genome sequencing. Proteomics is the comprehensive study of all types and types of proteins, especially those related to protein structure and functions.
Professor Claudia Langenberg, Director of the Precision Healthcare Research Institute at Queen Mary University of London, said that genetic data provides information about the body's biological blueprint, while protein measurements can provide a picture of how this blueprint works within the patient's body.
Researchers need to conduct additional studies that include larger numbers of patients, more diverse populations, and a broader range of rare diseases. Scientists also aim to increase the number of proteins that can be measured, improve the sensitivity of tests, and develop accurate reference ranges for interpreting results.
Although blood protein analysis is not currently a substitute for genome sequencing, the results indicate that it can become an important complementary tool that helps researchers discover biological signals that may remain hidden, and brings some patients closer to reaching a long-awaited diagnosis.
The health and wellness boom has led to a wide range of consumer products promising to improve health and happiness, but physician and journalist Zand van Tulleken talks to Grace Wade about three trends to watch out for, and points out their reasons.
In 1893, cowboy Clark Stanley killed rattlesnakes at the Chicago World's Fair, then boiled them and sold the fat extracted from them as a tonic to treat a variety of health problems, giving rise to the famous "snake oil" story. This trick may seem less convincing today, however, as the distinction between quackery and medicine has become more difficult; Health guidelines now compete with an ill-defined health and wellness industry, fueled by influencer podcasts and social media.
A journey to understand the world of health
In his book Make Me Well: A quest to understand the confusing world of wellness, physician and journalist Xand van Tulleken investigates this largely unregulated industry. It explains the things that keep people healthy, and the things that don't.
• Grace Wade: What exactly is “wellness”?
- Zand van Tulleken: Wellness is concerned with how we feel: improving performance, improving bodily functions, and perhaps reducing the risk of disease. But wellness insurance practices do not fall within the framework of health care.
• The modern wellness industry is trying hard to blur the boundaries between health and wellness. But what's the difference?
-The difference is that wellness is equivalent to improving health. The industry's intentional blurring of the lines between health and wellness, and the resulting confusion, prompted me to write Make Me Well. Health usually involves a specific, measurable problem, while health care is concerned with preventing or treating specific conditions. Wellness focuses on goals that are difficult to measure: feeling better, improving performance, and improving appearance.
Except for strictly controlled claims — such as vitamin C's ability to reduce fatigue — the wellness industry cannot claim that products treat medical problems. However, advertising rules do not prevent influencers from offering their opinions as advice.
While the healthcare industry protects the “minimum,” keeping people’s health within the normal range, the health and wellness industry promotes the “maximum,” inviting them to imagine the best version of themselves.
• Are there health products that improve health?
- certainly. I've examined nutritional supplements, wearables, and commercial tests. These products are similar to medications, but for most of them, the supporting evidence disappears upon scrutiny. These products are not designed to treat or diagnose diseases, and generally do not require any proof of effectiveness or safety; Because manufacturers avoid claiming that they provide any medical benefit.
The problem is that companies can still tout health benefits through less-scrutinized channels: the packaging may not carry a claim, while a podcaster might.
• Is there any harm in trying these products, such as vitamins, for example?
- Yes, vitamins are necessary, but healthy people usually do not need nutritional supplements. Accepting that supplements are not beneficial to healthy people has challenged my personal beliefs (as a doctor).
Doctors previously believed that nutritional supplements were safe and that excess nutrients were easy to control. However, large clinical trials conducted in the 2010s showed that multivitamins did not reduce deaths from serious diseases, while some antioxidant supplements increased mortality by between 4 and 16 percent, depending on their type and dose.
Antioxidant supplements may help protect cancer cells from damage. It remains unclear why fruits and vegetables do not cause the same risks; The body appears to process nutrients in whole foods differently.
Vitamins remain valuable treatments for diagnosed deficiencies, including vitamin B deficiency in beriberi and vitamin D deficiency in rickets.
Suspecting a deficiency in any nutrient is a health care concern. The doctor not only treats iron deficiency, for example, but also looks for other causes such as intestinal disease, pernicious anemia, and irregular menstruation, questions that promoters of nutritional supplements have no motive to ask.
Home checks and wearable technologies
• What about home examinations? It seems that they would be useful, rather than harmful, for detecting deficiencies and diseases.
-Commercial tests cover cancer, menopause, hormones and vitamin levels. However, comprehensive screening without medical indications may not save lives and may even deteriorate people's health.
In a large Finnish clinical trial of blood tests for prostate cancer, only about a third of positive results were confirmed by biopsy. Performing tests without other reasons for suspicion can lead to harmful tests, nerve damage, and unnecessary anxiety.
Doctors conduct tests after estimating a person's likelihood of contracting the disease. Interpretation of results depends on symptoms, medical history, and context.
I'm not against public health, I just want to save people time and money, and give them the freedom to do what matters to them.
• What about wearable technologies?
- I have my smart watch here with me, and while I doubt how useful this data on my heart rate, stress levels, and sleep is, I don't think it's hurt me.
The numbers provided by wearable devices simplify the complexities of life into a reassuring conclusion. For example, on an exercise bike, I know my heart rate and strength level accurately, whereas regular trials do not provide a similar objective measure.
Wearable devices may encourage excessive focus on data, pursuit of step counts, or reliance on exercise. For most people they simply provide numbers, and there is no evidence that they improve users' fitness.
However, I support expanding access to personal health information. Such as bathroom scales; Wearable devices can show whether something is moving in an overall beneficial direction.
The danger begins when consumer devices screen for diseases. Although some wearables are approved as medical devices, doctors and health companies use them very differently. A glucose monitor can be a lifesaver for people with diabetes, but users of health and wellness apps may consider normal blood sugar spikes dangerous. In order to avoid these increases, they may move away from fruits, legumes, and whole grains, and move towards eating more cheese and meat, which increases the risk of cardiovascular disease.
I tested a personalized nutrition service twice at the same time, using two glucose monitors, identical stool samples, blood samples from each arm, and identical personal data. The service showed mixed blood sugar and microbiome results, and conflicting nutritional advice, suggesting unreliability of the results.
Health myths
• If the health and wellness industry is full of myths, why do you think interest in it has increased so much in recent years?
The medical sector bears part of the responsibility for the increased interest in health and wellness. Access to health care can be difficult; Even in the United Kingdom, appointments are rare and short due to the small number of doctors.
Health care also does not meet the needs of some groups, especially women and minorities, who may find it difficult to obtain appropriate treatment.
Menopause makes this gap clear: consumers spend billions on nutritional supplements, while scientific research receives relatively little funding.
The United States spends about $57 million annually on menopause research, far less than the required $100 million, while spending in the United Kingdom is not even recorded and is in fact very small.
When menopausal symptoms become severe and science seems uninterested, turning to “wellness products” becomes understandable. Health care may seem paternalistic and restrictive, while wellness provides a sense of control.
Medicine also expresses uncertainty honestly. Here the nutritional supplement offers promises that something can happen; While the doctor may explain that the medication provides only a limited reduction in future risks and has side effects.
• What advice do you have for those who want to improve their health?
- Consult your healthcare professional before purchasing wellness products. Make sure to attend the recommended check-ups, know your blood pressure, and eat vegetables; These simple basics improve health.
You should go beyond health products. Satisfaction can come from community, family, friendship, and personal growth. I'm not against wellness products; I want people to save their time and money and focus on what really matters.
Find something you love — martial arts, knitting, dancing, or pottery — and get passionately into it. This may be the most effective way to maintain your health. It's okay to pursue biomodulation as a hobby, but don't expect products, supplements, special treatments, or stem cell programs to extend your life.
A new scientific study reveals unprecedented details about the way DNA regulates immune system cells after researchers succeeded in drawing the first three-dimensional, cell-level map of the human tonsil genome.
Scientists hope that this map, which describes the complex organization of genetic material within thousands of cells, will help understand the way immunity develops and why some normal immune processes can sometimes become a source of mutations associated with cancer. The study was published in the journal Science on July 23, 2026, and was conducted by a research team from Yale University School of Medicine in the United States, led by immunologist David Schatz from the Department of Immunobiology in cooperation with geneticist Siyuan (Stephen) Wang from the Department of Genetics at the same college.
“Spaghetti” inside the cell nucleus
Although the DNA in the body's cells can be about two meters long, it must be squeezed into a microscopic nucleus; Therefore, DNA is not straight, but rather twisted, bent, and intertwined into a complex structure that, according to researchers, resembles “a huge ball of pasta.” But this apparent chaos is not random. The way genetic material is folded and organized varies from one cell type to another and can determine which genes work, when they work, and how active they are.
To understand this organization, Wang's team used an advanced imaging technique developed in his laboratory known as Multiplexed Imaging of Nucleome Architectures (MINA). The technique allows imaging of DNA, RNA, and proteins inside cells, while they are still in their natural environment within the tonsil tissue.
The researchers say that this method enabled them to build the first three-dimensional atlas of the human tonsil genome at the cell level, and it also represents the first imaging-based three-dimensional genomic map of human organ tissue.
How do cells make better antibodies? The tonsils play an important role in the immune system. They contain specialized immune cells that help the body recognize and confront pathogens.
Scientists also focused specifically on B cells, which produce antibodies. After these cells are exposed to immune stimuli, they can undergo a recognition process
