Publications by authors named "Sayeh Kohani"

Article Synopsis
  • - Missense variants, which change a single amino acid in proteins, are linked to various human disorders but are challenging to interpret, with many labeled as "Variants of Unknown Significance."
  • - AlphaMissense, a new artificial intelligence tool, has been developed to predict the effects of these variants based on protein structure and has been tested against extensive experimental data from multiplexed assays (MAVE) measuring functional impacts.
  • - While AlphaMissense ranks among the top algorithms for predicting missense variant effects and shows good correlation with actual functionality, it, along with other predictors, tends to overestimate the pathogenicity of some variants, indicating a need for better training data and methods for more accurate assessments.
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How does wiring specificity of neural maps emerge during development? Formation of the adult olfactory glomerular map begins with the patterning of projection neuron (PN) dendrites at the early pupal stage. To better understand the origin of wiring specificity of this map, we created genetic tools to systematically characterize dendrite patterning across development at PN type-specific resolution. We find that PNs use lineage and birth order combinatorially to build the initial dendritic map.

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Transcription factors specify the fate and connectivity of developing neurons. We investigate how a lineage-specific transcription factor, Acj6, controls the precise dendrite targeting of Drosophila olfactory projection neurons (PNs) by regulating the expression of cell-surface proteins. Quantitative cell-surface proteomic profiling of wild-type and acj6 mutant PNs in intact developing brains, and a proteome-informed genetic screen identified PN surface proteins that execute Acj6-regulated wiring decisions.

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Neurons undergo substantial morphological and functional changes during development to form precise synaptic connections and acquire specific physiological properties. What are the underlying transcriptomic bases? Here, we obtained the single-cell transcriptomes of olfactory projection neurons (PNs) at four developmental stages. We decoded the identity of 21 transcriptomic clusters corresponding to 20 PN types and developed methods to match transcriptomic clusters representing the same PN type across development.

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