Biology subjects

Aragon, A.

Publications and source records attributed to Aragon, A..

4 recordsLinked to original sources

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↗

bioRxiv2025

Learning evolutionary parameters from genealogies using allelic trees

Cellular diversification in processes from development to cancer progression and affinity maturation is often linked to the appearance of new mutations, generating genetic heterogeneity. Describing the underlying coupled genetic and growth processes that result in the observed diversity in cell populations is informative about the timing, drivers and outcomes of cell fates. Current approaches based on phylogenetic methods do not cover the entire range of evolutionary rates, often making artificial assumptions about the timing of events. We introduce CBA, a probabilistic method that infers the division, degradation and mutation rates from the observed genetic diversity in a population of cells. It uses a summarized backbone tree, intermediary between the true cell tree and the allelic tree representing the ancestral relationships between types, called a monogram, which allows for efficient sampling of possible phylogenies consistent with the observed mutational signatures. We demonstrate the accuracy of our method on simulated data and compare its performance to standard phylogenetic approaches.

genetics↗

bioRxiv2024

Perception of task duration influences metabolic cost during split-belt adaptation and biomechanics during both adaptation and post-adaptation

Studies of locomotor adaptation have shown that adaptation can occur in short bouts and can continue for long bouts or across days. Information about task duration might influence the adaptation of gait features, given that task duration influences the time available to explore and adapt the aspects of gait that reduce energy cost. We hypothesized that information about task duration influences adaptation to split-belt walking based on two competing mechanisms: individuals anticipating a prolonged adaptation period may either (1) extend exploration of energetically suboptimal gait patterns, or (2) adapt toward a more energy-efficient pattern earlier to maintain an energetic reserve to sustain the task longer. We tested three groups: N=19 participants received minute-by-minute updates during a 10-minute adaptation duration (True group), N=19 participants received no updates during a 10-minute adaptation duration and were misled to expect a prolonged 30-minute adaptation duration (False group), and N=14 participants received one update halfway through a 10-minute adaptation duration (Control group). We measured step length asymmetry, leg work, and metabolic cost. Our results partially supported our hypothesis but did not confirm the underlying mechanisms. While step length asymmetry did not differ significantly between groups during adaptation, the True group generated a more effortful gait pattern with a greater increase in metabolic cost (p=0.002) and higher work with the leg on the slow belt (p=0.012). Additionally, the True group showed no association between step length asymmetry and metabolic cost (p=0.203), contrary to the Control (r=-0.55, p=0.043) and False groups (r=-0.51, p=0.027). Finally, we observed that the False group showed greater retention of the split-belt aftereffects than the Control and False groups (p<0.001). Thus, adapted locomotor and energetic patterns are influenced by information about task duration, indicating that Information about task duration should be controlled for, or can be manipulated to elicit different efforts during adaptation.

neuroscience↗

bioRxiv2023

Divergent warning patterns influence male and female mating behaviours in a tropical butterfly

Traits under divergent ecological selection that also function during mating can be important in maintaining species boundaries. Few studies have considered mutual mate choice, where both males and females base mating decisions on the same trait. We investigated the contribution of visual preference to assortative mating between an aposematic butterfly Heliconius cydno and its sympatric relative H. melpomene. Wing colouration in Heliconius butterflies evolved as a warning signal but also functions as a mating cue. We predicted that both sexes of H. cydno contributed to assortative mating by exhibiting visual preference towards conspecific wing colouration. We analysed published and new data from preference experiments, in which males were presented with conspecific and H. melpomene females. We also recorded female responses and mating outcomes in choice experiments, involving conspecific males with either the original white or artificially painted red forewing bands. Both sexes of H. cydno responded more positively towards the conspecific colouration, yet male colouration did not predict mating outcomes in female choice experiments. As courtships are initiated by males in butterflies, our findings suggest that female visual preference might be of secondary importance in preventing gene flow between H. cydno and H. melpomene.

animal behavior and cognition↗