Gergely, R. | Search bioRxiv

bioRxiv2026

Unveiling Cerebrospinal Fluid Protein Biomarkers in Pediatric Acute Lymphoblastic Leukemia Using Proximity Extension Assay

BackgroundAcute Lymphoblastic Leukemia (ALL) is a highly heterogeneous pediatric malignancy. Despite high survival rates, relapse and the involvement of central nervous system (CNS) remains a significant clinical challenge. Traditional clinical parameters often lack the precision required for early detection and risk stratification. This study utilizes high-throughput proteomics and machine learning (ML) to identify molecular signatures in cerebrospinal fluid (CSF) that characterize disease effect and treatment response. Methods82 CSF samples from 41 pediatric ALL patients at diagnosis (VD) and remission (VR) were analyzed. Proteomic profiling of 276 proteins was performed using Olinks Proximity Extension Assay. Differentially abundant proteins were identified (q-value< 0.05, |Log_2FC| > 0.5) using the Wilcoxon rank-sum test. Three ML algorithms - Random Forest, LASSO, and SVM-RFE - were integrated to select the differentially abundant proteins in VR and VD and between CNS involvement levels. To validate the data Pan-Cancer Atlas analysis was done using two different platforms. ResultsIn VR, we observed significant alterations in the expression of key proteins compared to VD, with ADGRG1 and KYNU showing a marked increase, while CCL17, CD5, CD27, CXCL9, CXCL11, FASLG, GZMA, and TNFRSF9 were significantly downregulated. Furthermore, our analysis identified distinct protein signatures associated with CNS involvement: CCL4, CTSC, CXCL10, CXCL9, and MMP7 were differentially abundant at the VD, whereas CAIX, CASP-8, HAGH, CXCL9, MMP7, MCP-2, and VWC2 at the VR. ConclusionIntegrating Olink proteomics with ML identified molecular signatures in ALL that have the potential to be further developed to a biomarker panel for monitoring treatment response and guiding personalized therapeutic strategies shifting the focus toward the Precision One Health approaches.

biochemistry↗

bioRxiv2020

Seasonal variation in sexual readiness in a facultatively sexual freshwater cnidarian with diapausing eggs

Facultative sexuality combines clonal propagation with sexual reproduction within a single life cycle. Clonal propagation enables quick population growth and the occupancy of favorable habitats. Sex, on the other hand, results in the production of offspring that are more likely to survive adverse conditions (such as the resting eggs of many freshwater invertebrates). In seasonal environments, the timing of sex is often triggered by environmental cues signaling the onset of winter (e.g. temperature drop or changes in photoperiod). Organisms switching to sex to produce resting eggs under these conditions face a trade-off: responding too early to an environmental cue increases the chances of missing out in clonal propagation, while having a delayed response to deteriorating conditions entails the risk of parental mortality before sexual reproduction could be completed. To mitigate these risks, increased sensitivity towards environmental cues with the onset of the winter might be an adaptive strategy. To test this hypothesis, we investigated sexual propensity and time to gonadogenesis in clonal strains derived from spring- and autumn-collected polyps of Hydra oligactis, a facultatively sexual freshwater cnidarian where sex only occurs prior to the onset of winter. We show that autumn-collected individuals and their asexual offspring have a higher propensity for sex and require less time for gonad development compared to strains established from spring-collected individuals that were kept under similar conditions in the laboratory. To see if the above results can be explained by phenotypic plasticity in sexual readiness, we exposed cold-adapted lab strains to different lengths of warm periods. We found that sexual propensity increases with warm exposure. Our results suggest that reciprocal cold and warm periods are required for sex induction in H. oligactis, which would ensure proper timing of sex in this species. Increased sensitivity to environmental deterioration might help maximize fitness in environments that have both a predictable (seasonal) and an unpredictable component.

ecology↗