Arctic mixed-phase clouds are peculiar objects: they contain both supercooled liquid droplets and ice crystals coexisting at temperatures well below freezing. During the polar night they warm the surface and contribute to sea ice decline, and the strength of that effect depends sensitively on microphysical properties such as liquid water path, ice water path, and the effective sizes of droplets and ice particles. Because climate models still struggle to represent the thermodynamic phase partitioning and water paths of these clouds, long-term ground-based observations are among the most valuable constraints available for model evaluation. The Arctic itself is warming two to four times faster than the global average, a phenomenon known as Arctic amplification, and uncertainty in its magnitude persists largely because models cannot accurately simulate the sensitivity of sea ice loss to rising global temperatures.

The study draws on data from the U.S. Department of Energy’s Atmospheric Radiation Measurement (ARM) North Slope of Alaska site in Utqiaǵvik, covering winters from 1 November to 30 April between 2011 and 2024. The researchers combined the Ka-band zenith-pointing cloud radar, a Vaisala CL31 ceilometer, a dual-frequency microwave radiometer, and radiosonde profiles to characterize cloud properties using the Cloudnet target classification algorithm. Sea ice conditions came from the AMSR2 satellite sensor, which provides daily sea ice concentration at roughly 3.1 kilometre resolution over the Chukchi-Beaufort region surrounding the site. The team also had to correct for a known observational blind spot: low-level liquid clouds below the radar’s lowest detection range, which account for roughly 22.5 to 26 percent of observations at the site, were handled by extrapolating radar reflectivity down to the lidar’s lowest liquid detection altitude of 10 metres.

A central methodological innovation, adapted from the team’s earlier MOSAiC work, is the identification of the specific upstream sea ice sector that actually influences a given cloud. Rather than averaging sea ice concentration over the entire surrounding region, the authors define a narrow conical sector, six degrees wide and extending 50 kilometres upwind, aligned with the direction of maximum water vapour transport in the atmospheric boundary layer. This matters because sea ice conditions in the full semi-circle around the station can differ substantially from those in the upwind cone; using large-scale averages risks ill-posed correlations between ice and cloud properties.

The water vapour transport itself serves as a conveyor belt linking the ice surface to the cloud. When the vertical gradient of water vapour transport reaches a local maximum within the cloud mixing layer, the cloud is classified as coupled to the sea ice system; otherwise it is decoupled. This distinction proved decisive. For coupled clouds, liquid water path increased clearly as sea ice concentration decreased, levelling off at median values of roughly 80 to 120 grams per square metre when ice concentration fell below about 30 percent. Decoupled clouds showed no significant relationship with sea ice concentration at all, echoing the MOSAiC result and extending its validity to ice concentrations as low as 5 percent.

The physical explanation lies in enhanced latent and sensible heat fluxes from leads and polynyas, which promote convection and the release of sea salt aerosols. When these plumes couple to overlying clouds, they drive up the cloud water content. Consistent with this, the effective radii of both droplets and ice particles increased as sea ice concentration decreased in coupled cases, a dependence that the MOSAiC study had not detected. Cloud geometry responded too: coupled clouds grew shallower as the ice thinned, while the temperature lapse rate within the cloud layer shifted from occasionally inverted conditions over nearly complete ice cover toward a moist adiabatic profile over open water, indicating cooling with height and stronger convective mixing. Ice water path showed no consistent change with sea ice concentration overall, though coupled cases under high-pressure systems displayed a strong positive correlation with decreasing ice concentration.

Weather systems added another layer of structure. The authors classified observations by local surface pressure, distinguishing high- and low-pressure regimes, and found that cloud properties depended on both coupling status and the prevailing pressure system. High-pressure conditions favoured decoupled clouds, occurring 56.3 percent of the time over the study period. Under low-pressure systems, coupled clouds consistently showed lower liquid-layer cloud base heights than their decoupled counterparts across all ice concentrations, a difference that only appeared at high ice concentrations under high-pressure regimes.

The long-term time series revealed statistically significant trends, and here the choice of statistical method proved critical. A conventional moving-average regression and a harmonic model that accounts for cyclical signals sometimes disagreed, particularly for decoupled clouds whose properties oscillate on short periods. The most striking results concern coupled clouds under low-pressure systems: the abstract reports a coupled liquid water path increase of 35.0 plus or minus 0.9 grams per square metre per decade, a cloud base height rise of 44.0 plus or minus 0.7 metres per decade, and a cloud top temperature warming of 2.2 plus or minus 0.7 kelvin per decade. The moving-average method alone yielded a coupled liquid water path trend of 24.3 plus or minus 0.7 grams per square metre per decade under low pressure and 4.4 plus or minus 0.7 grams per square metre per decade under high pressure. Decoupled clouds, by contrast, showed no significant trend in liquid water path or cloud top temperature, while their cloud base height declined under low-pressure conditions.

Perhaps the most intriguing finding is the cyclical character of the cloud time series. Liquid water path peaks aligned with strong El Niño events in 2016 and 2023, while minima coincided with the La Niña years from 2020 to 2022. By fitting the data to harmonic models whose frequencies were drawn from Fourier analysis of the El Niño-Southern Oscillation, Pacific Decadal Oscillation, and Arctic Oscillation indices, the authors found that most cloud parameters are best explained by ENSO periods of 5.4 and 10.8 years and PDO periods of 6.5 and 10.8 years, with shorter Arctic Oscillation contributions of 2.3 to 2.9 years. Coupled clouds oscillated on longer cycles than decoupled ones. The authors are careful to note that while the evidence supports a link to these climate modes, establishing a direct causal connection remains non-trivial.

The implications reach beyond cloud physics. Analyses of surface skin temperature suggest that continued warming in the Western Arctic is attributable to low-pressure conditions over open or partially open water, whereas under high-pressure systems with nearly complete ice cover, cloud radiative effects on surface temperature actually decreased. The authors argue that Arctic climate models must capture this full complexity, incorporating not only small-scale moisture transport from leads to clouds but also weather patterns, large-scale circulation, and Arctic-lower latitude teleconnections. Limitations remain, including the lack of vertically resolved aerosol measurements at the site and the use of local pressure as a proxy for synoptic systems. Even so, the study demonstrates the value of sustained, high-quality Arctic monitoring networks, and it hands modellers a robust observational benchmark against which to test how well their simulations reproduce the interplay between sea ice and the clouds that warm it.

Subject of Research: Long-term modulation of wintertime Arctic mixed-phase clouds by sea ice conditions and climate oscillations

Article Title: Western Arctic wintertime mixed-phase clouds: Observed modulation by sea ice conditions, long-term variabilities and trends

Article References: Saavedra Garfias, P., & Kalesse-Los, H. (2026). Western Arctic wintertime mixed-phase clouds: Observed modulation by sea ice conditions, long-term variabilities and trends. Atmospheric Chemistry and Physics, 26(20), 14843-14865. https://doi.org/10.5194/acp-26-14843-2026

Image Credits: AI Generated

DOI: 10.5194/acp-26-14843-2026

Keywords: Arctic, mixed-phase clouds, sea ice, North Slope of Alaska, liquid water path, MOSAiC, ENSO, Pacific Decadal Oscillation, Arctic amplification, cloud radiative effect, water vapour transport, ARM

The results document a substantial tumor yield in the selected surgical subgroup, although they do not establish an incidence for all children with the condition. Thirteen patients were admitted to the Department of Urology at the Children’s Hospital of Soochow University in Suzhou, China, between January 2016 and October 2023, and two additional patients were treated at the Qinghai Provincial Maternal and Child Health Hospital in Xining. Inclusion required a mosaic karyotype containing 45,X/46,XY cell lines and a normal female phenotype without ambiguity of the external genitalia.

The 13 Soochow patients underwent bilateral gonadectomy with salpingectomy, while the two Qinghai patients were followed in outpatient care without surgery. At the end of follow-up, the cohort had a mean age of 12.58 ± 3.02 years and a mean follow-up duration of 47.33 ± 30.78 months. Short stature or growth retardation was the main reason for the initial consultations.

Mean height rose from 124.39 ± 17.43 cm at presentation to 139.09 ± 17.76 cm at final follow-up. None of the children had signs of hyperandrogenism, including acne, hirsutism or virilization, and all had a Prader grade of 0 for external genital development. Three patients experienced menarche before gonadectomy.

Ultrasonography showed a rudimentary uterus and bilateral ovarian dysgenesis or streak gonads in every participant, and no definitive family history was reported. The uniformly female-appearing external phenotype therefore coexisted with internal gonadal dysgenesis and Y-containing cell lines. Peripheral-blood karyotyping established the diagnosis in nine children, accounting for 60% of the cohort, while fluorescence in situ hybridization, or FISH, detected the condition in the remaining six, or 40%.

The authors noted that a low percentage of mosaicism may become apparent when too few cells are tested or an inadequate number of tissues is sampled. On that basis, they considered supplementary molecular cytogenetic testing, including FISH and array-based diagnostics, useful when structural abnormalities of the sex chromosomes are identified. The present study did not perform systematic molecular analysis across all tissues, however, so the distribution of 45,X and 46,XY cells beyond the sampled material remained uncertain.

Pathological examination of the 13 surgical specimens found gonadoblastoma in four, or 30.77%. Three of these children had bilateral gonadoblastoma, while one had a lesion in the left gonad and a streak gonad on the right. The other nine operated patients had bilateral streak gonads without gonadoblastoma.

The reported ages of children with tumors ranged from 6.17 to 12.83 years, indicating that lesions were diagnosed across a substantial portion of childhood in this cohort. These observations cannot define a safe age threshold because the sample was small, follow-up was limited, and the two conservatively managed children provided no histological evidence about whether their gonads contained tumors. Gonadoblastoma was described in the research as a benign tumor composed of undifferentiated cells resembling those involved in gonadal development together with sex-cord derivatives.

The paper notes that it may develop into invasive dysgerminoma and can progress to other malignant germ-cell tumor types, while also citing no documented cases of metastatic disease or mortality attributed to gonadal malignancy in people with Turner mosaic syndrome containing Y material. The authors regarded the generally favorable prognosis as relevant to decisions about surgery, but the present youngest tumor at 6.17 years means that favorable outcomes observed elsewhere do not establish that an individual young child is free of risk. Before removal of dysgenetic gonads, the study’s management pathway included endocrine evaluation of gonadal function.

Measurements covered follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone and anti-Müllerian hormone. When clinically warranted, the investigators also used human chorionic gonadotropin and luteinizing hormone-releasing hormone stimulation tests, followed by gonadal biopsy in the described clinical approach. Retaining the gonads may permit spontaneous puberty, menstruation and possible fertility, but this potential benefit must be weighed against the tumor risk.

The authors’ conclusion favored prophylactic gonadectomy after an appropriate age while allowing postponement with regular monitoring in selected cases, emphasizing participation by patients in the decision rather than surgery at a single fixed chronological point. The two children managed without surgery underwent annual assessment using ultrasonography of the uterus and ovaries, serum biochemistry, a sex-hormone panel and measurement of growth hormone levels. Such surveillance could track anatomy and endocrine status but could not directly establish the presence or absence of gonadoblastoma, because neither patient had histological examination.

The retrospective design also meant that surgery and observation were not assigned randomly, and the two centers followed different management pathways. These features limit causal comparisons between the groups and make the 30.77% figure best interpreted as the histological yield among the 13 operated children rather than a universal population incidence. Twelve of the 15 children, or 80%, received growth hormone therapy at an initial dose of 0.15 IU/kg/day, which continued until the investigators considered the achieved height satisfactory.

The authors proposed considering discontinuation when growth potential was limited, including situations in which bone age exceeded 14 years or height gain fell below 2 cm per year. This growth-focused treatment was separate from gonadal management, and the observational design did not establish that gonadectomy produced the observed height increase. Overall, the study documents how karyotyping and FISH can identify Y-chromosome material in children with a female-appearing phenotype, records gonadoblastoma in 30.77% of those undergoing gonadectomy, and places surgery within an individualized assessment of endocrine function, tumor risk, reproductive potential and patient participation.

Published rates of gonadoblastoma in other small retrospective series have ranged widely, including 12% in a review of 43 patients, 28.6% in 14 patients, 35.5% in 20 patients, 10% in 10 patients and 57.1% in seven patients. Those figures are not directly interchangeable with the present result because sampling, follow-up and pathological assessment differed, and small retrospective cohorts are vulnerable to selection bias. The authors acknowledged their own study’s retrospective design, small sample and incomplete tissue-level molecular analysis.

Within those limits, the evidence shows that Y-chromosome material may be present despite a female-appearing phenotype, that karyotyping and FISH each contributed to diagnosis, and that dysgenetic gonads require endocrine evaluation and carefully individualized decisions about surveillance, gonadectomy and involvement of the patient and family.

Subject of Research: Clinical characteristics, diagnosis, gonadal pathology and management of Turner mosaic syndrome with Y-chromosome material in children.

Article Title: Turner mosaic syndrome with Y chromosome material: characteristics, diagnosis, and management

Article References: Wang, T., Zeng, G., Cao, X., Xia, H., Zhang, T., Yan, X., & Fu, M. (2026). Turner mosaic syndrome with Y chromosome material: characteristics, diagnosis, and management. Frontiers in Pediatrics, 14, Article 1948778. https://doi.org/10.3389/fped.2026.1948778

Image Credits: AI Generated

DOI: 10.3389/fped.2026.1948778

Keywords: Turner mosaic syndrome, Y chromosome, gonadoblastoma, gonadectomy, pediatric urology, FISH, karyotyping, gonadal dysgenesis, endocrine monitoring, retrospective cohort, Turner, mosaic

The research team, led by investigators from the N.N. Blokhin National Medical Research Center of Oncology and the Engelhardt Institute of Molecular Biology in Moscow, enrolled 18 patients ranging in age from one month to 21 years. All had congenital craniofacial nevi and a variable array of extracutaneous abnormalities affecting the brain, eyes, heart, kidneys, bones, and endocrine system. The central diagnostic challenge in this field is that the clinical entities overlap so heavily that the nevus subtype, whether sebaceous, spilus, or melanocytic, has traditionally been the main feature used to classify the disease. Schimmelpenning–Feuerstein–Mims syndrome, for instance, is defined by linear nevus sebaceous, while phacomatosis pigmentokeratotica requires that same nevus in combination with a speckled lentiginous nevus, or nevus spilus. Yet the same mosaic variants in RAS/MAPK pathway genes, primarily HRAS and KRAS, have been found across all of these conditions, blurring the boundaries between them.

To cut through this ambiguity, the team turned to targeted next-generation sequencing. DNA was extracted from peripheral blood leukocytes, from the nevus tissue itself, from unaffected skin, and, where available, from tumor tissue. Libraries were prepared with the KAPA HyperPrep kit and hybridized to customized capture probes covering the coding regions of RAS/MAPK pathway genes. Sequencing was performed on an Illumina NextSeq 2000 instrument with an average coverage of 250 to 350 times, ensuring that at least 90 percent of the target region was covered at 50-fold or greater depth. The pipeline aligned reads to the GRCh38/hg38 reference genome, called variants with GATK, and applied a minimum variant allele frequency threshold of 2 percent, a cutoff chosen deliberately because mosaic variants are present in only a fraction of cells and can be missed by conventional methods. All candidate variants were then verified by Sanger sequencing, although the authors acknowledge that Sanger has a practical detection limit of roughly 15 to 20 percent variant allele frequency, meaning low-level mosaics rest on the NGS findings alone.

The results were striking in their consistency. Every pathogenic or likely pathogenic variant, in the genes HRAS, KRAS, BRAF, PIK3CA, and FGFR2, was present exclusively in affected tissues and entirely absent from peripheral blood DNA and normal skin. Variant allele frequencies ranged from 17 percent to 84 percent in the lesions. Eight patients received a diagnosis of Schimmelpenning–Feuerstein–Mims syndrome, four carrying postzygotic HRAS variants and four carrying KRAS variants. Seven patients met the clinical criteria for phacomatosis pigmentokeratotica, with mosaic variants identified in HRAS in four cases, KRAS in two, and BRAF in one. In two additional patients with similar skin phenotypes, the culprit turned out to be a somatic mutation in PIK3CA in one case and FGFR2 in the other, pointing to entirely different diagnostic categories, while in one final patient no clinically significant variant was detected at all.

The clinical narratives behind these genetic findings are extraordinary. One nine-year-old boy with craniofacial linear nevus sebaceous developed skeletal deformities and classic rickets from the age of one year. Standard treatment with phosphate and alfacalcidol failed, so at age four he was started on burosumab, a monoclonal antibody against fibroblast growth factor 23. After fifteen months of therapy, his pain resolved, independent walking returned, and his alkaline phosphatase, serum phosphorus, and calcium levels normalized. Genetic testing of his nevus revealed a pathogenic HRAS variant, c.182A>G (p.Gln61Arg), with a variant allele frequency of 62 percent. Another four-year-old boy with the same syndrome developed alveolar rhabdomyosarcoma, a malignant soft tissue tumor, in the paratesticular region, with metastases to the femur and hand. After nine courses of polychemotherapy he has remained in remission for more than two years, and sequencing showed the HRAS variant at 17 to 22 percent in the nevus but a striking 84 percent in the tumor itself, a pattern consistent with a two-stage mechanism in which the HRAS mutation drives tumor formation and subsequent loss of heterozygosity delivers the second hit.

Patients with KRAS variants told a different clinical story. One five-year-old girl with a KRAS c.35G>A (p.Gly12Asp) variant in her nevus had seizures from four months of age, MRI findings of bilateral trigeminal nerve lipomatosis, ventriculomegaly, and hydrocephalus, a rhabdomyoma in the right ventricle of the heart, epibulbar dermoids, retinal calcifications, and severe cognitive impairment. A twelve-year-old boy with the identical KRAS variant had epilepsy from early infancy, underwent temporal lobe resection that revealed a gangliocytoma, and experienced profound developmental delay, walking at nearly two years and speaking only at five. A twenty-one-year-old woman with pharmacoresistant epilepsy, focal cortical dysplasia, an arteriovenous malformation of the spine, renal angiomyolipomas, retinal hamartomas, and self-aggression requiring antipsychotic therapy also carried a KRAS variant in her nevus, undetectable in blood exome sequencing.

To move beyond individual anecdotes, the researchers conducted a systematic literature review spanning 1946 to 2025, searching PubMed and ResearchGate for genetically confirmed cases of epidermal nevus syndrome, Schimmelpenning–Feuerstein–Mims syndrome, phacomatosis pigmentokeratotica, and related mosaic RASopathies. They ultimately combined their own data with published cases to yield 53 cases with postzygotic HRAS variants and 41 cases with KRAS variants for genotype–phenotype correlation analysis. Statistical comparisons used Fisher’s exact test with Benjamini–Hochberg correction for multiple comparisons across eleven clinical features, controlling the false discovery rate at a threshold of q less than 0.05. Odds ratios were calculated with KRAS as the reference group, and the Haldane correction was applied to contingency tables containing zero cells to enable stable estimation.

The correlations that emerged were both statistically robust and clinically actionable. Ophthalmological disorders were dramatically overrepresented in KRAS-mutated patients, occurring in 71 percent versus 21 percent of HRAS-mutated cases, with an odds ratio of 9.2 and a confidence interval of 3.6 to 23.8. Coloboma, choristoma, and epibulbar dermoid were detected only in patients with KRAS variants. Neurological disorders, including epilepsy and various brain malformations, were also more common in KRAS-mutated patients, at 78 percent versus 40 percent, with an odds ratio of 5.4. Cardiovascular disorders and lymphatic malformations followed the same pattern, with odds ratios of 3.7 and 7.2 respectively. In sharp contrast, hypophosphatemic rickets was diagnosed exclusively in HRAS-mutated patients, occurring in 30 to 40 percent of cases, and malignant tumors were also more frequent in the HRAS group, at 36 percent versus 12 percent, with an odds ratio of 4.0. Among the malignancies, embryonal and alveolar rhabdomyosarcoma predominated in childhood, while skin cancer, urothelial carcinoma, and astrocytoma have been described in adults.

The mutational spectrum itself showed recurring hotspots. In the study cohort, the most common HRAS substitution was Q61R at 50 percent, followed by G13R at 37 percent, whereas in the literature the most frequent substitution was HRAS G13R at 57 percent. The G12D substitution predominated among all KRAS pathogenic variants, both in the study, where it accounted for 83 percent of cases, and in the literature, where it accounted for 64 percent. All six patients with KRAS variants in the study had congenital craniofacial linear nevus sebaceous, and two also had nevus spilus. In the published KRAS cases, linear nevus sebaceous was noted in 68 percent, and only one patient also had nevus spilus, a finding indicative of phacomatosis pigmentokeratotica.

Based on these findings, the authors propose a practical algorithm for establishing somatic mosaicism in epidermal nevus syndromes. Because variant allele frequencies can vary across a lesion, biopsies should be taken from at least four different areas of the nevus, and ideally from different types of nevi when feasible, and genetic testing of peripheral blood should always be performed in parallel to exclude germline pathogenic variants associated with hereditary syndromes that can mimic the mosaic phenotype. This dual approach proved decisive in several cases: a patient initially suspected of having Schimmelpenning–Feuerstein–Mims syndrome turned out to carry a PIK3CA variant, placing her in the PIK3CA-Related Overgrowth Spectrum category, while another patient with a mosaic BRAF variant presented a differential diagnosis between mosaic cardiofaciocutaneous syndrome and phacomatosis pigmentokeratotica. The authors also emphasize that these genotype–phenotype correlations are probabilistic rather than deterministic, and that all patients with characteristic skin lesions should be referred for assessment by a multidisciplinary team of specialists. Nevertheless, the specific mosaic genotype can, with appropriate caution, inform prognosis, guide surveillance for the complications most likely to arise, and support the development of targeted therapies, from MEK inhibitors for refractory epilepsy to anti-FGF23 antibodies for hypophosphatemic rickets. In a field where the visible lesion is only the tip of the molecular iceberg, sequencing the affected tissue has become the compass that points the way forward.

Subject of Research: Mosaic RASopathies and genotype–phenotype correlations in postzygotic RAS/MAPK pathway mutations

Article Title: Mosaic RASopathies: comprehensive genetic and clinicopathological analysis for diagnosis and management

Article References: Belysheva, T., Nasedkina, T., Zelenova, E., Semenova, V., Semenova, N., Sagoyan, G., Kletskaya, I., Vishnevskaya, Y., Sharapova, E., Kulikova, K., Vlasov, P., Botkina, A., Belogurova, M., Dorofeeva, M., Valiev, T., & Varfolomeeva, S. (2026). Mosaic RASopathies: comprehensive genetic and clinicopathological analysis for diagnosis and management. Frontiers in Cell and Developmental Biology, 14, Article 1908228. https://doi.org/10.3389/fcell.2026.1908228

Image Credits: AI Generated

DOI: 10.3389/fcell.2026.1908228

Keywords: mosaic RASopathies, epidermal nevus syndrome, Schimmelpenning–Feuerstein–Mims syndrome, phacomatosis pigmentokeratotica, HRAS, KRAS, genotype–phenotype correlation, next-generation sequencing, rhabdomyosarcoma, hypophosphatemic rickets, Mosaic, RASopathies

The initiative, called MOSAIC (Multi-Omics Spatial Atlas in Cancer), is a multi-center clinical omics study that has profiled more than 2,700 cancer samples spanning multiple tumor types. The consortium brings together researchers from Owkin and clinical and academic partners including Gustave Roussy in France, Charité Universitätsmedizin Berlin and University Hospital Erlangen in Germany, Lausanne University Hospital in Switzerland, and the University of Pittsburgh in the United States. The study was funded by Owkin Inc. and conducted as a non-interventional, multicenter clinical protocol, registered as NCT06625203, with ethics approval at each participating site. What distinguishes MOSAIC from many previous atlas projects is not just its size but its deliberate integration of data modalities that are usually collected and analyzed in isolation.

Technically, each tumor sample in MOSAIC is characterized through several complementary lenses. Spatial transcriptomics captures gene expression across intact tissue sections, preserving the two-dimensional geography of the tumor and allowing researchers to measure which genes are active at which coordinates on a slide. Single-nuclei transcriptomics resolves expression at the level of individual cells, distinguishing malignant subclones from the diverse non-malignant cells of the tumor microenvironment. These are layered alongside digitized histology scans, bulk whole-transcriptome sequencing, and whole-exome sequencing, which together provide the genomic mutations, the aggregate expression landscape, and the classical pathological view of the tissue. Extensive curated clinical information, including treatment regimens and outcomes, is attached to each sample, so that molecular patterns can eventually be linked to how patients actually responded.

The rationale for this multi-modal design is that no single technology can capture the full complexity of a tumor. Histology reveals architecture but not molecular identity; bulk sequencing averages away the very heterogeneity researchers want to measure; single-cell methods lose spatial context; and spatial methods, until recently, lacked single-cell resolution. By generating all of these representations from the same samples under standardized protocols, MOSAIC aims to create a resource in which computational methods, including artificial intelligence, can learn to connect what a pathologist sees under the microscope with what the genome and transcriptome reveal, and ultimately to identify clinically relevant biomarkers and cancer subtypes that no single modality alone could expose.

Alongside the full study design, the consortium has released an initial public dataset called the MOSAIC Window, now available through the European Genome-phenome Archive under study ID EGAS50000000689. This first release covers 60 patients across five tumor types and includes quality-controlled data from spatial transcriptomics, single-nuclei RNA sequencing, bulk RNA sequencing, and whole-exome sequencing, together with curated clinical descriptors such as age, smoking status, disease stage, and survival. The consortium describes this release as a glimpse into the project’s potential, with further data releases planned as the study matures. The cohort design spans eleven major cancer types overall, including bladder, breast, colorectal, gastric, glioblastoma, head and neck squamous cell carcinoma, mesothelioma, non-small cell lung cancer, ovarian, and pancreatic cancers, sampled at baseline diagnosis, after neoadjuvant therapy, and at recurrence or progression.

The early analyses reported in the paper demonstrate the analytical power that comes from combining these modalities. Using the MOSAIC Window data, the researchers quantified both intra-patient and inter-patient heterogeneity, uncovering distinct malignant cell subsets within individual tumors. They then examined how these malignant subpopulations relate to their surroundings and found a correlation between the intrinsic oncogenic signaling activity of malignant cells and the colocalization of specific tumor microenvironment cell types. In other words, the signaling programs running inside cancer cells appear to be associated with which immune and stromal cells gather around them, a link that could help explain why some tumor regions are immunologically cold and others inflamed, and why immunotherapy can succeed in one part of a tumor while failing elsewhere.

To make these concepts concrete, the paper presents four diverse case studies, each illustrating a different way that integrated multi-omics data can decipher heterogeneity. In these examples, the team used computational tools such as differential expression analysis and gene set enrichment analysis to characterize malignant cell clusters identified from single-nuclei data, and quantified pathway activities with methods like PROGENy and GSVA to compare signaling states across subpopulations. Statistical measures, including variance analyses and Pearson correlations between spot-level cellular fractions, were used to test whether the associations between malignant signaling and microenvironment composition were robust across samples and indications. The case studies span different tumor types and different biological questions, collectively highlighting how the same standardized data framework can support a wide range of investigations.

The technical rigor behind the resource is considerable. Supplementary documentation accompanying the paper details quality metrics for every modality, from median gene counts per spatial spot and read-mapping percentages in transcriptomics to sequencing depth, contamination estimates, and GC content in whole-exome data. A detailed data management plan describes how samples are pseudonymized, how data flows across modalities are linked to a common study identifier, and how the resource adheres to FAIR principles, making the data findable, accessible, interoperable, and reusable. The clinical study protocol, covering objectives, endpoints, eligibility criteria, and the statistical analysis plan, is also published, giving the community full visibility into how the resource was constructed.

For the field of computational oncology, the significance of MOSAIC lies partly in addressing a persistent bottleneck: the scarcity of large, consistent, well-annotated datasets. Machine learning models for histology and multi-omics integration have advanced rapidly, but they are often trained on small or inconsistently processed cohorts, limiting their generalizability and clinical translation. A standardized atlas of thousands of tumors, each with matched spatial, single-cell, genomic, histological, and clinical data, provides exactly the kind of training substrate that multimodal artificial intelligence approaches require. The consortium explicitly states its aim to use artificial intelligence and other computational approaches to integrate all data modalities and extract clinically actionable insights, positioning MOSAIC as infrastructure for the next generation of biomarker discovery.

There are, of course, caveats worth noting. The study is funded entirely by a single company, Owkin, and several authors are current or former employees holding shares or stock options in the company, alongside a range of disclosed consulting relationships with pharmaceutical and diagnostics firms at the academic sites. The paper is published as a shared early version, citable with a permanent DOI and subject to further editorial updates. And while the MOSAIC Window release demonstrates feasibility and analytical promise, the clinical value of the resource will ultimately depend on whether the biomarkers and subtypes it reveals can be validated prospectively and shown to improve patient outcomes. Still, with more than 2,700 samples profiled, an open first dataset already in researchers’ hands, and a standardized framework linking molecular, spatial, and clinical dimensions of cancer, MOSAIC represents one of the most ambitious attempts yet to map the internal diversity of tumors at scale, and a foundation on which the precision oncology community can build for years to come.

Subject of Research: Multi-omics characterization of intra-tumoral heterogeneity using spatial and single-cell profiling in cancer

Article Title: MOSAIC: Intra-tumoral heterogeneity characterization through large-scale spatial and cell-resolved multi-omics profiling

Article References: MOSAIC Consortium, Cornish, A. J., Bayard, Q., Karabajakian, A., Madissoon, E., Ferrarini, G., Youssef, A., Badoual, C., de Leval, L., Dressman, D., Durand, E. Y., Erber, R., Florian, S., Garberis, I., Haignere, C., Homicsko, K., Keilholz, U., Lee, A. V., Lehar, J., … Hoffmann, C. (2026). MOSAIC: Intra-tumoral heterogeneity characterization through large-scale spatial and cell-resolved multi-omics profiling. Genome Medicine. https://doi.org/10.1186/s13073-026-01791-y

Image Credits: AI Generated

DOI: 10.1186/s13073-026-01791-y

Keywords: MOSAIC, intra-tumoral heterogeneity, spatial transcriptomics, single-nuclei RNA-seq, multi-omics, tumor microenvironment, precision oncology, whole-exome sequencing, cancer biomarkers, artificial intelligence, Genome Medicine, open data