Evans, W. | bioRxiv Science

bioRxiv2025

Measuring Longitudinal Genome-wide Clonal Evolution of Pediatric Acute Lymphoblastic Leukemia at Single-Cell Resolution

Approximately 15-20% of children with acute lymphoblastic leukemia (pALL) are not cured despite years of treatment with more than ten chemotherapeutic agents, yet bulk sequencing reveals minimal somatic variation that could explain genetic treatment resistance. Using error-corrected bulk sequencing, and primary template-directed amplification (PTA)-enabled single-cell exome and whole-genome sequencing, we discovered much more genetic diversity in pALL. Individual leukemic cells harbor 3.7-fold more mutations (mean 3,553) than detected in bulk samples (mean 965). Many ETV6-RUNX1 patients harbor multiple independent ras-mutated clones, and we also identified convergent evolution of JAK2 mutations as well as copy number alterations. PTA-based phylogenetic analysis of over 150 single-cell genomes linked heritable phenotypes to specific genetic alterations and identified low-frequency clones harboring mutations in treatment resistance-associated genes (ITGA9, NTRK3, SULF2) that increased in frequency during treatment. These findings reveal extensive hidden genetic diversity in pALL while providing a framework for the early detection of high-risk leukemic populations.

cancer biology↗

bioRxiv2024

The potential applications of high-resolution 3D scanners in the taxonomic classification of insects

The phenotypic classification of small biological specimens, such as insects, can be dependent on phenotypic features that are difficult to observe and communicate to others. Here, we evaluate how high-resolution 3D photogrammetric scanner technology can potentially allow such features to be resolved and visualised as a 3D models, which can then be shared as a taxonomical resource for species identification, as virtual type specimens, and for educational and public engagement purposes. We test the viability and limitations of this approach using specimens digitised with a Artec Micro scanner. Ten samples from unique species were mounted and scanned. The model outputs were evaluated against an identification key, which compiled diagnostic features for the specimens from the wider literature, to describe the specimens to the lowest taxonomic level possible. The results showed that six of the ten specimens could be identified to species level using the scans. Threshold values for body length and width were 10.7 mm and 4.4 mm respectively. Below these body dimensions important diagnostic features of specimens could not be resolved reliably. This result suggests that with current technology, 3D photogrammetric modelling is a viable method for taxonomic identification of a wide range of insect groups with larger body sizes. This approach opens up novel applications for species identification and data sharing among taxonomists, international field research, conservation efforts, and entomological outreach. However, the limitations of this approach to taxonomic identification must be considered depending upon the size of the specimen and its diagnostic features. Future developments in the technology and processing methods used may alleviate the constraints on body size exhibited in this study, widening the applications for smaller bodied specimens.

scientific communication and education↗