Biology subjects

Melchor, J.

Publications and source records attributed to Melchor, J..

6 recordsLinked to original sources

bioRxiv2024

MerQuaCo: a computational tool for quality control in image-based spatial transcriptomics

Image-based spatial transcriptomics platforms are powerful tools often used to identify cell populations and describe gene expression in intact tissue. Spatial experiments return large, high-dimensional datasets and several open-source software packages are available to facilitate analysis and visualization. The outputs of spatial transcriptomics platforms are typically imperfect. For example, local variations in transcript detection probability are common. Software tools to characterize imperfections and their impact on downstream analyses are lacking so the data quality is assessed manually, a laborious and often a subjective process. Here we describe imperfections in a dataset of 641 fresh-frozen adult mouse brain sections collected using the Vizgen MERSCOPE. Common imperfections included the local loss of tissue from the section, tissue outside the imaging volume due to detachment from the coverslip, transcripts missing due to dropped images, varying detection probability through space, and differences in transcript detection probability between experiments. We describe the incidence of each imperfection and the likely impact on the accuracy of cell type labels. We develop MerQuaCo, open-source code that detects and quantifies imperfections without user input, facilitating the selection of sections for further analysis with existing packages. Together, our results and MerQuaCo facilitate rigorous, objective assessment of the quality of spatial transcriptomics results.

bioinformatics↗

bioRxiv2023

Crossmodal correspondence of natural amplitude modulations

Crossmodal correspondence is the ability to recognize objects from different sensory modalities to be similar. Here, we investigated the capacity of humans to perform crossmodal discriminations between visual, acoustic, and tactile stimuli modulated in amplitudes of low-pass filtered envelopes obtained from natural sounds. We found that the perception of crossmodal correspondence emerged from the number of amplitude prominences in each stimulus rather than from temporal variations. Therefore, we propose saliency as the supramodal trade coin of temporal modulations.

neuroscience↗

bioRxiv2020

Neuronal Correlates of the Perceptual Invariance of Words and Other Sounds in the Supplementary Motor Area of Macaques

The supplementary motor area (SMA) of the brain is critical for integrating memory and sensory signals into perceptual decisions. For example, in macaques, SMA activity correlates with decisions based on the comparison of sounds.1 In humans, functional MRI shows SMA activation during the invariant recognition of words pronounced by different speakers.2 Nevertheless, the neuronal correlates of perceptual invariance are unknown. Here we show that the SMA of macaques associates novel sounds with behaviors triggered by similar learned categories when recognizing sounds such as words. Notably, the neuronal activity at single and population levels correlates with the monkeys behaviors (e.g. hits and false alarms). Our results demonstrate that invariant recognitions of complex sounds involve premotor computations in areas other than the temporal and parietal speech areas. Therefore, we propose that perceptual invariance depends on motor predictions and not only sensory representations. We anticipate that studies on speech will observe sensory-motor transformations of acoustic information into motor skills.

neuroscience↗

bioRxiv2020

Auditory Decisions in the Supplementary Motor Area

In human speech and communication across various species, recognizing and categorizing sounds is fundamental for the selection of appropriate behaviors. But how does the brain decide which action to perform based on sounds? We explored whether the premotor supplementary motor area (SMA), responsible for linking sensory information to motor programs, also accounts for auditory-driven decision making. To this end, we trained two rhesus monkeys to discriminate between numerous naturalistic sounds and words learned as target (T) or non-target (nT) categories. We demonstrated that the neural population is organized differently during the auditory and the movement periods of the task, implying that it is performing different computations in each period. We found that SMA neurons perform acoustic-decision-related computations that transition from auditory to movement representations in this task. Our results suggest that the SMA integrates sensory information while listening to auditory stimuli in order to form categorical signals that drive behavior.

neuroscience↗

bioRxiv2019

Evolutionary Origins of Recurrent Pancreatic Cancer

Surgery is the only curative option for Stage I/II pancreatic cancer, nonetheless most patients will recur after surgery and die of their disease. To identify novel opportunities for management of recurrent pancreatic cancer we performed whole exome or targeted sequencing of 10 resected primary cancers and matched intrapancreatic recurrences or distant metastases. We identified that adjuvant or first-line platinum therapy corresponds to an increased mutational burden of recurrent disease. Recurrent disease is enriched for mutations that activate Mapk/Erk and PI3K/AKT signaling and develops from a monophyletic or polyphyletic origin. Treatment induced genetic bottlenecks lead to a modified genetic landscape and subclonal heterogeneity for driver gene alterations in part due to intermetastatic seeding. In one patient what was believed to be recurrent disease was an independent (second) primary tumor. These findings advocate for combination therapies with immunotherapy and routine post-treatment sampling as a component of management of recurrent pancreatic cancer.

cancer biology↗

bioRxiv2019

Invariant recognition of words and naturalistic sounds in non-human primates

The ability to invariably identify spoken words and other naturalistic sounds in different temporal modulations and timbres requires perceptual tolerance to numerous acoustic variations. However, the mechanisms by which auditory information is perceived to be invariant are poorly understood, and no study has explicitly tested the perceptual constancy skills of nonhuman primates. We investigated the ability of two trained rhesus monkeys to learn and then recognize multiple sounds that included multisyllabic words. Importantly, we tested their ability to group unexperienced sounds into corresponding categories. We found that the monkeys adequately categorized sounds whose formants were at close Euclidean distance to the learned sounds. Our results indicate that macaques can attend and memorize complex sounds such as words. This ability was not studied or reported before and can be used to study the neuronal mechanisms underlying auditory perception.

neuroscience↗