Radically different
Nature Biotechnology, Published online: 22 April 2026; doi:10.1038/s41587-026-03106-3
This Comment discusses depth, robustness and bias in plasma proteomics, concluding that increasing the depth of coverage does not necessarily translate to quantitative robustness.
Nature Medicine, Published online: 15 April 2026; doi:10.1038/s41591-026-04337-2
For individuals with APOL1 high-risk genotypes, which are enriched in individuals of African ancestry, a nine-protein proteomic risk score enables early prediction of kidney disease progression and may, thereby, enable early intervention.
Nature Medicine, Published online: 13 April 2026; doi:10.1038/s41591-026-04326-5
This Resource presents a large-scale analysis of nearly 3,000 circulating plasma proteins across the menstrual cycle in over 2,700 women from the UK Biobank, revealing distinct proteomic patterns across menstrual phases. This work sheds light on female reproductive biology and gynecological disorders, and provides a proteomic signature for accurate prediction of the menstrual cycle phase.
A limiting feature of many neurological therapies is the ability of molecules to cross the blood-brain barrier (BBB) from the circulatory system. Since the BBB prevents simple diffusion of materials across the divide, identifying the proteins responsible for transport is necessary for effective design of BBB-crossing therapies.
“So basically, everything in the circulating blood, if they want to have an exchange with the organ, they need to pass through this interface,” says senior author Jiefu Li, PhD, Janelia Research Campus Group Leader at the Howard Hughes Medical Institute.
Identification of the structures within blood vessels involved with the processes of molecular movement across the BBB has been somewhat elusive. However, Li and his team have developed a technique that not only identifies proteins within the luminal surface—the inner lining—of the vasculature, but also works in vivo, allowing them to track how these features change across the aging brain.
“Understanding how the blood-brain barrier works, particularly figuring out the molecular targets that you can play with to open and close the barrier, will provide new possibilities for drug delivery,” Li says.
Their work is published in Science in a paper entitled, “Luminal surface proteome of the brain vasculature uncovers blood-brain barrier regulators.”
Using mice, the team developed a proteomic profiling method that can be used not only in brain vasculature, but throughout the body. “Briefly, a lectin-conjugated peroxidase is perfused and anchored to the luminal surface of blood vessels to catalyze the biotinylation of adjacent proteins, thereby enabling subsequent protein enrichment and mass spectrometry analysis,” wrote the authors.
They tested the method in the brain, kidney and intestine, in both mice and northern tree shrew, showing functionality and applicability across organs and species.
“This will allow us to say: we know that the vasculature system is doing different things in different organs and it relies on this luminal surface, but how does that happen? What are the molecular players there?” Li says.
Using quantitative proteomics of the luminal surface—from early development through adulthood and aging—they found that over time there was a decrease in angiogenic and transport proteins. They also found an increase in proteins that increased stiffness in the vasculature.
In addition to developing this in vivo technique, the team identified two proteins that are temporally distinct in their expression while both playing a role in modulating BBB permeability. Knockouts of nitric oxide synthase Nos3 and arginine transporter Slc7a1 resulted in BBB leakage in neonates, but not adults, while genetic screens identified hyaluronidase HYAL2 as being required for maintaining BBB integrity throughout the lifespan of mice.
“What we know now is that we have two new pathways, potentially, to open the blood-brain barrier and to inform some therapeutic developments,” says Li.
Utilization of this proteomic based method in vivo both opens up new avenues of functional research across the cardiovascular system, and also provides data and a methodology for novel therapeutic targets for crossing the BBB.
“This method solves an important need but it’s also a very easy-to-use method, so everyone can use it,” Li says.
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This week, Seer, a developer of proteomics technology, said that scientists involved in the PRECISE-SG100K initiative will use the company’s Proteograph® product suite to profile the plasma proteome of about 10,000 participants. The data from this workflow will be combined with information from the same participants that was generated using Thermo Fisher Scientific’s Olink® Reveal, a next-generation sequencing-based proteomics solution, and its Orbitrap Astral
mass spectrometers.
PRECISE-SG100K is the second phase of a broader initiative in Singapore that aims to support various research studies that advance scientists’ understanding of health and diseases. Touted as a landmark population study of approximately 100,000 Singaporean residents, PRECISE-SG100K is designed to integrate genomic, proteomic, lifestyle, imaging, and other health data from a multi-ancestry Asian population. By combining data from Seer’s Proteograph platform alongside information from other technologies that are being used for the project, the scientists aim to develop what they believe will be one of the most comprehensive multiomic datasets available to date.
“PRECISE-SG100K is one of the most ambitious and carefully designed multiomic health initiatives in the world,” said Omid Farokhzad, MD, PhD, chair and CEO of Seer. And that fits with Seer’s vision for Proteograph, which was that “deep, unbiased proteomics becomes the mainstay for population-scale multiomic studies.”
Seer already has an existing relationship with Thermo Fisher dating back several years. In 2024, the companies announced a co-marketing and sales agreement that allowed Thermo to jointly promote Proteograph alongside Orbitrap Astral mass spectrometers to provide customers of the Orbitral Astral with an integrated solution for unbiased proteomic analysis. The combined solutions have since been used in a number of large population studies providing high-throughput, deep proteome coverage.
“A key goal of PRECISE-SG100K is to create a deeply characterized, multi-ancestry resource that can reveal how genetics, environment, and lifestyle shape disease risk and treatment response,” said John Chambers, PhD, chief scientific officer of PRECISE and lead principal investigator of the PRECISE-SG100K study. “By adding deep, unbiased plasma proteomics enabled by Seer and Thermo Fisher, we can more directly link genomic variation to protein networks and health outcomes, uncovering insights critical to ensuring precision medicine reflects the diversity of Asian populations.”
Ultimately, the data generated from population projects like this are expected to support biomarker discovery in key disease areas including cardiometabolic, ophthalmic, and neurologic disorders. They could also inform the development of predictive models for assessing disease risk and response as well as efforts to validate and prioritize biomarkers identified through affinity-based platforms.
The post Seer to Apply Deep Proteomics Tech to Singapore Population Cohort Study appeared first on GEN – Genetic Engineering and Biotechnology News.
Plant molecular farming (PMF) may seem like a bold option for companies accustomed to mammalian or microbial systems, but recent advances have transformed plant-based bioproduction into serious, scalable biomanufacturing platforms able to produce even complex biologics cost-effectively.
“A major advantage is sustainability,” Marco P.C. Marques, PhD, associate professor, University College London (UCL), tells GEN. This comes at a time when “…regulators and global initiatives are putting real pressure on industry to reduce environmental footprint(s). Because plants grow using low energy inputs rather than stainless steel reactors or energy-intensive systems, they can bring down operating costs, reduce carbon emissions, and provide more flexible manufacturing options.”
Additional benefits include PMF systems’ ability to support eukaryotic protein-folding and post-translational modification pathways, their lack of human pathogens, minimal biosafety risks, and compatibility with distributed manufacturing.
PMF reached its current state because sensors, host plant engineering, AI-enabled models, and related technologies have become more mature, reliable, and predictable in the past few years. Consequently, “PMF platforms can deliver consistent, good manufacturing practice (GMP)-compatible performance while needing far less infrastructure, [which] allows much faster setup than conventional approaches,” Marques says.
In a recent paper, he and first author Teresa Iucci, PhD, a bioprocessing scientist at Sapienza University of Rome and UCL, cite 13 companies that are using or have used plants to produce a variety of proteins, including antibodies, enzymes, and peptides, for vaccines and other biologics. Many are at clinical or commercial scale.
Those examples show “that controlled cultivation, advanced transient-expression systems, and more refined downstream workflows can overcome many of the technical and regulatory hurdles historically associated with plant-based biomanufacturing.” In particular, they note substantial improvements in host plant engineering. Now, they point out, Nicotina plants can produce mAbs and Fc-fusion proteins that closely match those derived from CHO cells.
However, “Realizing the full value of these biological innovations will depend on aligning PMF with contemporary digital manufacturing principles,” Iucci and Marques stress.
“There is a lot of scope for continued innovation…particularly on the molecular biology side, where further gains in expression, stability, and product quality are very achievable,” Marques elaborates. “Downstream processing could also be better tailored to plant-based hosts,” to lower costs further.
The benefits of PMF are well-recognized, but biomanufacturers also need clear, streamlined regulatory pathways and the internal determination that PMF is worth sustained investment.
For biomanufacturers, “A good starting point is simply to treat PMF as a genuine production platform rather than an interesting alternative,” he says. To be able to compare PMF products with those derived from traditional mammalian or microbial cultures, he calls for the industry to standardize unit operations and generate regulatory-grade datasets, and then to run comparability studies and pilot-scale campaigns.
Running such campaigns is becoming increasingly practical with the conjunction of sensors and data-driven processors. In vertical farming facilities, for example, every parameter critical for plant growth is tightly monitored and controlled using digital sensors to enable precise, real-time environmental adjustments.
Ultimately, this allows producers to select the optimal timing of such events as infiltration and harvest at levels not possible in conventional greenhouses. “The long-term objective is a semi-continuous, digitally regulated PMF production line that links infiltration, extraction, and purification into a coherent, self-correcting workflow,” Iucci and Marques write.
Transitioning from mammalian or microbial systems to PMF, “is easier said than done…especially when companies already have well-established mammalian or microbial platforms with validated processes and established supply chains,” Marques acknowledges. “In many respects, it would be simpler to design a PMF-based approach from scratch than to retrofit it into an existing operation…but with the right incentives (such as additional revenue streams from side processes), application cases, and evidence, we may well see more companies prepared to make that shift.”
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