Transcriptomics

…liver systems, high-content imaging, transcriptomics, proteomics and ADME measurements. Its reasoning agent integrates those results with partner assays, chemical-series context, exposure estimates and clinical evidence to assess mechanistic liver-safety risks. Rather than using a single cell-toxicity score, the approach develops interpretable, series-specific structure–toxicity hyp

Reliably identifying cell types is crucial for understanding neural systems (1). However, classifying the neurons recorded in large-scale population recordings into well-defined types remains a challenge. While some methods rely on genetic targeting or anatomy for classification, a functional approach used in sensory systems is to analyze neuronal responses to stimuli that elicit distinguishable responses across different types (2, 3, 4). Yet, previous approaches of this nature have been limited by a restricted set of stimuli and scalability issues, thus preventing comprehensive characterizati

The development of autism spectrum disorder (ASD) is strongly influenced by genetic factors. To navigate the large number of genes associated with the disorder, recent efforts have been directed towards finding functional convergence among ASD-risk genes. Within the biological processes commonly affected in ASD, cell proliferation is of particular interest, given the occurrence of brain volume anomalies in a significant subset of the ASD population. Since neural stem cells are key players in the expansion of neural cell pools throughout development, we hypothesized that a group of ASD-risk gen

Duchenne Muscular Dystrophy (DMD) is an X-linked neuromuscular disorder characterized by progressive muscle degeneration, severe inflammation, and premature death of young adults. In addition to physical disability, DMD presents largely non-progressive neuropsychiatric abnormalities, impacting patient compliance with treatment and overall quality of life for both patients and their families. The disease arises from mutations in the DMD gene, which encodes structurally and functionally distinct dystrophins. Notably, individuals with DMD lack full-length isoforms present in crucial brain regions

Primary mitochondrial diseases are caused by mutations in genes that perturb mitochondrial function and frequently affect the nervous system in patients. Complex I deficiency is the most common childhood mitochondrial disease and is caused by mutations in genes encoding complex I structural or assembly components. In patients, mutations in the complex I subunit NDUFS1 typically cause severe and rapidly progressive leukoencephalopathy and death during childhood. We developed a Drosophila model of complex I deficiency using knockdown of the NDUFS1 homolog ND-75 in neurons (ND-75 KD). ND-75 KD fl

…approach, including single nuclei transcriptomics, cell-type specific Hi-C 3D genome mapping, and viral integration site sequencing (IS-seq) to frontal lobe tissue from HIV-infected individuals with encephalitis (HIVE) and without encephalitis (HIV+). We observed reorganization of open/repressive (A/B) compartment structures in HIVE microglia encompassing 6.4% of the genome

Abuse, neglect, and other forms of uncontrollable stress during childhood and early adolescence can lead to adverse outcomes later in life, including especially perturbations in the regulation of mood and emotional states, and specifically anxiety disorders and depression. However, stress experiences vary from one individual to the next, meaning that causal relationships and mechanistic accounts are often difficult to establish in humans. This interdisciplinary talk considers the value of research in experimental animals where stressor experiences can be tightly controlled and detailed investi

…gene expression data from single-cell transcriptomics. Our current classification includes 43 types, accounting for 90% of the cells in EyeWire. Many of these cell types have new stories to tell, and I will cover two of them that represent opposite ends of the spectrum of levels of analysis in my lab. First, I will introduce the “Bursty Suppressed-by-Contrast” RGC and s

…this problem from a cell type and transcriptomics perspective. This reveals a more granular picture, where different cell types and classes have followed independent trajectories of evolutionary cha