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Gonzalez-Ferrer, J.

Publications and source records attributed to Gonzalez-Ferrer, J..

6 recordsLinked to original sources

Decoding brain anatomy from neuronal neighborhoods with MYCEL

Extracellular recordings carry information about neuronal location, and pooling per-unit predictions across neighboring electrodes improves its readout, but whether this local pooling should be learned is untested. We present MYCEL (Message-passing Yields Cellular Embeddings of Location), a graph neural network whose nodes are spike-sorted units carrying waveform and spike-timing features selected on cell-type ground truth, and whose edges encode recording geometry. On the Allen Brain Observatory Visual Coding Neuropixels dataset, learned message passing outperforms fixed aggregation, with the largest gains where single units are least informative. On the International Brain Laboratory Brain Wide Map, MYCEL matches the strongest population model at one-tenth the pairwise interactions. On held-out animals, the embeddings recover laminar depth within visual cortex. Retrained with only the edge geometry changed, the same framework decodes anatomy in macaque visual cortex and human medial temporal lobe. Thus, how neighboring neurons are combined matters as much as the features that describe them.

neuroscience↗

Cloud-Connected Pluripotent Stem Cell Platform Enhances Scientific Identity in Underrepresented Students

Stem cell research offers unique opportunities for authentic scientific engagement, yet infrastructure requirements have confined participation to elite institutions, perpetuating workforce disparities. We developed an integrated framework combining engineered biology, cloud-connected microscopy, and validated psychometric assessment to make pluripotent stem cell (PSC) experimentation widely accessible. The framework comprises three components: a doxycycline-inducible NGN2 mouse embryonic stem cell line for rapid neuronal specification, low-cost cloud microscopy for remote observation, and the validated Stem Cell Research Identity Scale (SCRIS) for quantifying educational outcomes. Implementation across a Title I high school and urban community college demonstrated significant increases in scientific identity. Students using differentiating PSCs showed broader science identity development than those using neuroblastoma cells, particularly in competence, research readiness, and recognition. High school students showed enhanced research competence gains compared to community college students despite equivalent intervention duration. Demographic analyses revealed enhanced effectiveness for Hispanic and first-generation college students. This framework provides a scalable model for broadening participation in advanced biomedical research.

scientific communication and education↗

HIPPIE: A Multimodal Deep Learning Model for Electrophysiological Classification of Neurons

Extracellular electrophysiological recordings present unique computational challenges for neuronal classification due to noise, technical variability, and batch effects across experimental systems. We introduce HIPPIE (High-dimensional Interpretation of Physiological Patterns In Extracellular recordings), a deep learning framework that combines self-supervised pretraining on unlabeled datasets with supervised fine-tuning to classify neurons from extracellular recordings. Using conditional convolutional joint autoencoders, HIPPIE learns robust, technology-adjusted representations of waveforms and spiking dynamics. This model can be applied to electrophysiological classification and clustering across diverse biological cultures and technologies. We validated HIPPIE on both in vivo mouse recordings and in vitro brain slices, where it demonstrated superior performance over other unsupervised methods in cell-type discrimination and aligned closely with anatomically defined classes. Its latent space organizes neurons along electrophysiological gradients, while enabling batch and individual corrected alignment of recordings across experiments. HIPPIE establishes a general framework for systematically decoding neuronal diversity in native and engineered systems.

neuroscience↗

Fate plasticity of interneuron specification

The generation of neuronal subtypes in the mammalian central nervous system is driven by competing genetic programs. The medial ganglionic eminence (MGE) gives rise to two major cortical interneuron (cIN) populations, marked by Somatostatin (Sst) and Parvalbumin (Pvalb), which develop on different timelines. The extent to which external signals influence these identities remains poorly understood. Pvalb-positive cINs are particularly important for regulating cortical circuits through strong perisomatic inhibition, yet they have been difficult to model in vitro. Here we investigated the role of the environment in shaping and maintaining Pvalb cINs. We grafted mouse MGE progenitors into a variety of 2D and 3D co-culture models, including mouse and human cortical, MGE, and thalamic systems with dissociated cells, organoids, organotypic cultures, and conditioned media. Across models, we observed distinct proportions of Sst- and Pvalb-positive cIN descendants. Strikingly, grafting MGE progenitors into 3D human, but not mouse, corticogenesis models led to efficient, non-autonomous differentiation of Pvalb-positive cINs. This differentiation was characterized by upregulation of Pvalb maturation markers, downregulation of Sst-specific markers, and the formation of perineuronal nets. Furthermore, lineage-traced postmitotic Sst-positive cINs, when grafted onto human cortical models, also upregulated Pvalb expression. These results reveal an unexpected level of fate plasticity in MGE-derived cINs, demonstrating that their identities can be dynamically shaped by the surrounding environment.

neuroscience↗

Open-loop lab-on-a-chip technology enables remote computer science training in Latinx life sciences students

Despite many interventions, science education remains highly inequitable throughout the world. Among all life sciences fields, Bioinformatics and Computational Biology suffer from the strongest underrepresentation of racial and gender minorities. Internet-enabled project-based learning (PBL) has the potential to reach underserved communities and increase the diversity of the scientific workforce. Here, we demonstrate the use of lab-on-a-chip (LoC) technologies to train Latinx life science undergraduate students in concepts of computer programming by taking advantage of open-loop cloud-integrated LoCs. We developed a context-aware curriculum to train students at over 8,000 km from the experimental site. We showed that this approach was sufficient to develop programming skills and increase the interest of students in continuing careers in Bioinformatics. Altogether, we conclude that LoC-based Internet-enabled PBL can become a powerful tool to train Latinx students and increase the diversity in STEM.

scientific communication and education↗

A data-efficient deep learning tool for scRNA-Seq label transfer in neuroscience

Large single-cell RNA datasets have contributed to unprecedented biological insight. Often, these take the form of cell atlases and serve as a reference for automating cell labeling of newly sequenced samples. Yet, classification algorithms have lacked the capacity to accurately annotate cells, particularly in complex datasets. Here we present SIMS (Scalable, Interpretable Ma-chine Learning for Single-Cell), an end-to-end data-efficient machine learning pipeline for discrete classification of single-cell data that can be applied to new datasets with minimal coding. We benchmarked SIMS against common single-cell label transfer tools and demonstrated that it performs as well or better than state of the art algorithms. We then use SIMS to classify cells in one of the most complex tissues: the brain. We show that SIMS classifies cells of the adult cerebral cortex and hippocampus at a remarkably high accuracy. This accuracy is maintained in trans-sample label transfers of the adult hu-man cerebral cortex. We then apply SIMS to classify cells in the developing brain and demonstrate a high level of accuracy at predicting neuronal sub-types, even in periods of fate refinement, shedding light on genetic changes affecting specific cell types across development. Finally, we apply SIMS to single cell datasets of cortical organoids to predict cell identities and unveil genetic variations between cell lines. SIMS identifies cell-line differences and misannotated cell lineages in human cortical organoids derived from different pluripotent stem cell lines. When cell types are obscured by stress signals, label transfer from primary tissue improves the accuracy of cortical organoid annotations, serving as a reliable ground truth. Altogether, we show that SIMS is a versatile and robust tool for cell-type classification from single-cell datasets.

bioinformatics↗