Biology subjects

Bianchi, J.

Publications and source records attributed to Bianchi, J..

4 recordsLinked to original sources

bioRxiv2026

Specific Aneuploidies Predict Immune Evasion and Poor Immunotherapy Response in Melanoma

Melanoma is one of the leading cancer types treated with immune checkpoint blockade (ICB), yet a substantial proportion of patients fail to respond. While tumor mutational burden and PD-L1 expression are established ICB biomarkers, they leave large gaps in predictive accuracy. Somatic copy number alterations (SCNAs) are pervasive in melanoma but their role in shaping the tumor immune microenvironment (TME) and predicting immunotherapy outcomes has been insufficiently characterized. Here we present KaryoTME, an integrated computational framework that systematically links SCNAs to immune phenotypes using genomic, transcriptomic, and clinical data from over 15,000 patients. Applying this framework to skin melanoma (SKCM) within a pan-cancer context, we identify arm-level chromosome 1q gain and 9p loss as the most prominent SCNA events associated with an immune-cold tumor microenvironment. These alterations act through distinct mechanisms: 9p loss preferentially depletes NK and CD8+ T cells, whereas 1q gain is more strongly associated with reduced anti-tumor immune cell infiltration. At the focal level, regions 1q21 and 1q42 show the strongest immune-suppressive associations in melanoma. Applying the TUSON-Immune algorithm, we predict candidate Tumor immune Suppressor Genes (TiSG) and immune Oncogenes (iOG) within these chromosomal regions, revealing enrichment for pathways including IFN signaling, JAK/STAT pathway, and immune-suppressive cytokine secretion. Critically, 1q gain emerged as a strong and independent predictor of poor survival following anti-PD-1/PD-L1 therapy across two independent clinical cohorts: the MSK-IMPACT cohort (p = 0.018, N = 77) and a large real-world Caris Life Sciences dataset (HR = 1.2, p = 0.002, N = 1,167). Multivariate analysis confirmed that 1q gain predicts poor outcomes independently of CD8+ T-cell infiltration, B-cell infiltration, tumor mutational burden, and PD-L1 status. These findings establish chromosome 1q gain as a compelling biomarker of immunotherapy resistance in melanoma and highlight aneuploidies as underappreciated drivers of immune evasion in this disease.

cancer biology↗

bioRxiv2026

RAPID DECLINE OF NESTING PEREGRINE FALCONS IN THE SAN FRANCISCO BAY REGION OF CALIFORNIA SYNCHRONOUS WITH AN H5N1 OUTBREAK

After rebounding from near extirpation during the organochlorine era, breeding Peregrine Falcons (Falco peregrinus) in California are again facing adversity, this time consistent with an outbreak of a highly pathogenic avian influenza. Following the first detection of the H5N1 variant clade 2.3.4.4b virus in California wild birds in July 2022, we assembled data from long-term monitoring (2000-2025) of peregrine breeding territory occupancy in the broad vicinity of San Francisco Bay to examine possible impacts on falcon populations. Prior to the outbreak, 47 focal breeding territories had shown nearly complete occupancy by pairs (98.5% of 390 site-years), with very few vacancies, single birds in attendance, or subadult pair members. Within 8 mo of the outbreak, occupancy had dropped to 65.1%, and 2 yrs later (2025), only 36.2% of sites remained occupied. An uptick in site-occupancy by single birds also occurred after the outbreak, but it is unclear whether these were survivors or floaters attempting to fill vacant territories where both pair members had perished. The high vacancy rates signaled an impact upon floaters (nonbreeding adults) that normally buffer breeding site-occupancy in healthy peregrine populations. From October 2022 through November 2025, 17 peregrine fatalities were diagnosed with H5N1 within the counties comprising our study area. Evidence that H5N1 caused these territory vacancies includes, (1) the striking temporal coincidence of occupancy loss with the outbreak, and (2) the lethality of the virus to peregrines and its confirmed presence in peregrine prey in our study area. Our study reaffirms the value of long-term territory occupancy monitoring in this sentinel species.

ecology↗

bioRxiv2018

PrimPol is required for the maintenance of efficient nuclear and mitochondrial DNA replication in human cells

Eukaryotic Primase-Polymerase (PrimPol) is an enzyme that maintains efficient DNA duplication by repriming replication restart downstream of replicase stalling lesions and structures. To elucidate the cellular requirements for PrimPol in human cells, we generated PrimPol-deleted cell lines and show that it plays key roles in maintaining active replication in both the nucleus and mitochondrion, even in the absence of exogenous damage. Human cells lacking PrimPol exhibit delayed recovery after UV-C damage and increased mutation rates, micronuclei and sister chromatin exchanges but are not sensitive to genotoxins. PrimPol is also required during mitochondrial replication, with PrimPol-deficient cells having increased mtDNA copy number but displaying a significant decrease in replication rates. Deletion of PrimPol in XPV cells, lacking functional Pol Eta, causes an increase in DNA damage sensitivity and pronounced fork stalling after UV-C treatment. We show that, unlike canonical TLS polymerases, PrimPol is important for allowing active replication to proceed, even in the absence of exogenous damage, thus preventing the accumulation of excessive fork stalling and genetic mutations. Together, these findings highlight the importance of PrimPol for maintaining efficient DNA replication in unperturbed cells and its complementary roles, with Pol Eta, in damage tolerance in human cells.

genetics↗

bioRxiv2018

Does pixel/voxel-size limit the measurement of distances in CBCT-tomography?

The necessity to obtain relevant structural information from tomographic images is an all-pervasive step in a host of clinical and research-areas. Cone Beam Computed Tomography (CBCT) is the imaging modality often used among the many available.\n\nCurrently approaches to extract structural properties from raw CBCT-images, involve some manual intervention by experts to measure their properties, such as size and displacements of their geometrical structures. Regarding the factors limiting the precision of these measurements, such as voxel-size and image contrast, we find conflicting statements in the literature. It is therefore useful to provide accurate data under well-defined experimental conditions.\n\nHere we present a method and associated software to measure displacements of geometrical structures. We also determined the minimum measureable displacement and minimum detectable defect in terms of voxel size. We select as our geometrical structure a sample of bovine bone and to provide a set of defects, we drilled a pattern of holes into it. We determined the holes three-dimensional structures using confocal spectroscopy.\n\nIn order to obtain the minimum measurable displacement, we acquired CBCT-tomographies containing a stationary reference and micro-metrically cnc controlled displacements of the sample. We then process these images with our software to extract the distances and compare them with the cnc displacements. All our processing includes a computational interpolation from the voxel-size of 0.35 mm corresponding to our CBCT-tomographies, down to 0.05 mm. We find that sample-displacements can be measured with a precision of ~ 20, 17 times smaller than the voxel-size of 0.35 mm.\n\nTo measure the size of the holes using our CBCT-tomographies, we first register the holes onto a hole-free region of the sample with our software, then overlay the result with the three-dimensional structure obtained from confocal spectroscopy. We find the minimum detectable hole-size to be 0. 7 mm, twice the voxel-size.

bioengineering↗