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Cardenas, C.

Publications and source records attributed to Cardenas, C..

9 recordsLinked to original sources

PIANO: Probabilistic Inference Autoencoder Networks for multi-Omics enables robust generative modeling of gene expression and scales single-cell integration to 100 million cells

Single-cell RNA technologies enable the routine acquisition of transcriptomic atlases. However, these molecular profiles are influenced by overlapping sources of variation. Since these covariates confound comparisons, data integration is the first step in most analyses. Three challenges remain: correcting strong batch effects, scaling to millions of cells, and modeling how covariates influence gene expression. To address these challenges, we developed PIANO: Probabilistic Inference Autoencoder Networks for multi-Omics, a deep learning framework whose central feature is a generative model of gene expression data. Additionally, PIANO achieves robust integrations and trains 10x faster than previous methods. PIANO accurately integrates single-cell data across species and across single-cell and spatial transcriptomics modalities. As practical applications, PIANO models spatially-resolved gene expression during Alzheimer's disease progression in human brains and integrates over 100 million cancer cells to model drug perturbations. In summary, PIANO's integration and generative modeling capabilities will empower novel insights for countless future studies.

bioinformatics↗

Lessening the bottleneck: reduced spatiotemporal overlap between krill fishing vessels and post-fledging chinstrap penguins led to increased apparent survival

Fledging is a critical period of a seabird life cycle. Using satellite telemetry, we compared movements and survival proxies (transmission duration) of chinstrap penguin fledglings tracked in 2017 (n=8) and 2025 (n=17) relative to krill fishing vessel activity. In 2017, fishing vessels operated intensively near colonies during summer, resulting in early, frequent encounters (median 1.3 days post-fledging) and short transmission durations (median 9.2 days). In 2025, reduced fishing delayed encounters (median 10.0 days) and tripled tracking duration (median 24.0 days). Hidden Markov Models revealed that vessel encounters reduced the probability of transitioning from foraging to transit behavior ({beta} = -0.76), an effect stronger than the productivity ({beta} = -0.11). While 87.5% of 2017 fledglings ceased transmission prematurely within weeks (half of those right after entering areas intensively used by fishing vessels), 65% of 2025 fledglings survived beyond March, with half of those five transmitting until May after dispersing eastward to the South Orkney Islands. These findings suggest that spatiotemporal overlap with krill fisheries during the critical post-fledging window affected foraging behavior and was associated with shorter transmission durations. Our results support further research of post-fledging penguin ecology to better understand the potential impact of fishery, and, following the precautionary principle, support fishing seasonal protection of important areas during critical periods of krill predators life cycle.

ecology↗

Spatial patterning of transcriptional and regulatory programs in the primate subcortex

Mammalian brain cell identity is shaped by intrinsic factors and external context. We present a spatially resolved transcriptomic and gene regulatory atlas of cell types across all subcortical regions in a primate, the common marmoset. Dense sampling and cross-species integration revealed spatially precise neuronal assemblies, including in complex midbrain and diencephalic structures. Chromatin accessibility and transcriptional identity are spatially tuned within and across subcortical structures; spatial gradients within hippocampal subfields are orchestrated by graded transcription factors acting through graded enhancers. The primate-expanded thalamic GABAergic population shares transcriptional and regulatory syntax with conserved midbrain populations, reflecting an evolutionary adaptation compared with rodents. Similar regional expression across cell types can arise by distinct regulatory architectures, as for telencephalic astrocytes and neurons. Conversely, distant cell types can share regulatory programs despite divergent identities: striatal GABAergic medium spiny neurons and telencephalic glutamatergic neurons share a postsynaptic regulatory program despite divergent lineage, region, and neurotransmitter identity.

neuroscience↗

Fast Optimization of Robust Transcriptomics Embeddings using Probabilistic Inference Autoencoder Networks for multi-Omics

Advances in single-cell genomics technologies enable the routine acquisition of atlases with millions of cells. These datasets often include multiple covariates, such as donors, sequencing platforms, developmental timepoints, and species, which provide new opportunities for discovery and new challenges. To mitigate unwanted sources of variation, dataset integration is the starting point for most analyses. However, existing methods struggle with integrating large complex datasets. To address these limitations, we developed PIANO, a variational autoencoder framework that uses a negative binomial generalized linear model for stronger batch correction, and code compilation for ten times faster training than existing tools. We first demonstrate performant integration compared to commonly used methods on single-species datasets. We then show PIANO enables superior analyses of multiple atlases, solving challenging integration tasks across sequencing platforms, development, and species, while simultaneously preserving desired biological signals. Our contributions include a novel, high-performance integration method and recommendations for integration applications.

neuroscience↗

Understanding the molecular activity of Gibbilimbol B on human breast cancer cells

The authors have withdrawn this manuscript because the decision is based on the impossibility of publishing the article without obtaining the required authorization from the Colombian environmental government, as per national regulations concerning research involving biodiversity and natural resources.Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

biochemistry↗

Disparate estimates of intrinsic productivity for Antarctic krill across small spatial scales, under a rapidly changing ocean.

Understanding the spatio-temporal dynamics of Antarctic krill (Euphausia superba) productivity along the Western Antarctic Peninsula (WAP) requires the application of robust analytical approaches. Both design-based and model-based methodologies have been employed to address this challenge. The Spawning Potential Ratio (SPR) provides valuable insights about population indicators. In this study, we analyzed the spatial and temporal variability of the SPR for Antarctic krill by applying a Length-Based Spawning Potential Ratio (LBSPR) model to 20 years of fishery-dependent length composition data. Results showed spatial and temporal heterogeneity among fishing strata in the WAP, where Gerlache Strait stratum was consistently lower than the 20% SPR reference point, compared with Elephant, Bransfield Strait, South West and Joinville strata. Moreover, we demonstrate the sensitivity of LBSPR to changes in growth parameters, such as k and Linf, which are influenced by environmental variables like chlorophyll. Our findings underscore the necessity of incorporating environmental variability into stock assessment models, such as those based on SPR, to accurately assess krill stock conditions. Given the apparent spatial heterogeneity in intrinsic productivity identified through our SPR estimates, we propose using this approach to establish a management procedure based on a control rule for each stratum. This method adjusts the allocation of catch limits in line with the new management strategy of the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR). By integrating knowledge about spatial krill dynamics and its intrinsic productivity, advice can be recommended to ensure the sustainable management of krill populations in Subarea 48.1.

ecology↗

The anti-angiogenic compound dimethyl fumarate inhibits the serine synthesis pathway and increases glycolysis in endothelial cells

A pathological and persistent angiogenesis is observed in several diseases like retinopathies, diabetes, psoriasis and cancer. Dimethyl fumarate, an ester from the Krebs cycle intermediate fumarate, is approved as a drug for the treatment of psoriasis and multiple sclerosis, and its anti-angiogenic activity has been reported in vitro and in vivo. However, it is not known whether dimethyl fumarate is able to modulate endothelial cell metabolism, considered an essential feature for the angiogenic switch. By means of different experimental approximations, including proteomics, isotope tracing and metabolomics experimental approaches, in this work we studied the possible role of dimethyl fumarate in endothelial cell energetic metabolism. We demonstrate for the first time that dimethyl fumarate promotes glycolysis and diminishes cell respiration, which could be a consequence of a down-regulation of serine and glycine synthesis through inhibition of PHGDH activity in endothelial cells. This new target can open a new field of study regarding the mechanism of action of dimethyl fumarate.

biochemistry↗

Improving Lab Culture Through Self-Assessment: A Case Study

PurposeMotivated by perceived dissatisfaction within our labs changed working environment brought about by the COVID-19 pandemic, we performed a self-assessment of our lab culture through anonymous surveys and live sessions. MethodsIn Survey 1, we asked each lab member to identify and rank up to 10 values that are important for a healthy lab environment. They were then asked to rate how well the lab embodied those values at two time points: before the COVID-19 pandemic while working onsite, and at the time of the survey while working remotely (10 months into the pandemic). In a series of live group sessions, we reviewed relevant literature and the survey results to finalize ten themes. We then reflected on each theme and proposed action items to address any deficiencies. Finally, we conducted Survey 2 after the self-assessment to judge the groups finalized themes, implemented changes, and overall satisfaction with the assessment process. ResultsThemes identified were attitude, accountability, teamwork/collaboration, communication, diversity/inclusion, emotional intelligence, integrity, training, well-being, and adaptability in crisis-management. All lab members liked the self-assessment process and felt their voices were heard. On average, there was a 12% increase in satisfaction across all themes from the start to end of the lab assessment. ConclusionWe successfully assessed the culture of our lab and subsequently improved lab member satisfaction. The success of this team project suggests that other scientific labs could benefit from similar interactive self-assessments.

scientific communication and education↗

Warm Temperatures, Cool Sponges: The Effect of Increased Temperatures on the Antarctic Sponge Isodictya sp.

Although the cellular and molecular responses to exposure to relatively high temperatures (acute thermal stress or heat shock) have been studied previously, only sparse empirical evidence of how it affects cold-water species is available. As climate change becomes more pronounced in areas such as the Western Antarctic Peninsula, it has become crucial to understand the capacity of these species to respond to thermal stress. Here we use the Antarctic sponge Isodictya sp. to investigate how sessile organisms (particularly Porifera) can adjust to acute short-term heat stress, by exposing this species to 3 and 5 {degrees}C for 4 hours, corresponding to predicted temperatures under high-end 2080 IPCC-SRES scenarios. Assembling a de novo reference transcriptome (90,188 contigs, >93.7% metazoan BUSCO genes) we have begun to discern the molecular componentry employed by Isodictya to adjust to environmental insult. Our initial analyses suggest that TGF-{beta}, ubiquitin and hedgehog cascades are involved, alongside other genes. However, the degree and type of response changed little from 3 to 5 {degrees}C, suggesting that even moderate rises in temperature could cause stress at the limits of this organisms capacity. Given the importance of sponges to Antarctic ecosystems, our findings are vital for discerning the consequences of increases in Antarctic ocean temperature on these and other species.

genomics↗