Biology subjects

Najaf Panah, M. J.

Publications and source records attributed to Najaf Panah, M. J..

3 recordsLinked to original sources

bioRxiv2026

Transcriptional and DNA Methylation Changes in the Hippocampus and Prefrontal Cortex after Fractionated Cranial Radiation in Mice

Fractionated whole-brain irradiation is essential for treating brain tumors, but many long-term survivors develop cognitive decline whose molecular basis is poorly understood. We asked which cell types and gene programs change late after irradiation, how the hippocampus and prefrontal cortex compare, and whether DNA methylation changes affect the same genes or programs. Male and female mice received whole-brain irradiation (5 x 4 Gy) or anesthesia alone. Irradiated mice showed persistent deficits in executive function and spatial memory. Eleven weeks after irradiation, single-nucleus RNA sequencing and whole-genome bisulfite sequencing of pooled hippocampal (CA1-3) and prefrontal tissue showed cell-type-specific transcriptional changes in neurons of both regions. Both regions showed reduced ribosomal-protein gene expression and changes in adhesion genes, with reduced respiratory-chain genes in prefrontal neurons and bidirectional synaptic gene changes in hippocampus. Differentially methylated regions were enriched at promoters, with hypermethylation predominating in three of the four sex-by-region contrasts. Methylation and gene expression changes pointed to overlapping synaptic and signaling programs, largely through different genes.

neuroscience↗

bioRxiv2024

Coordinated regulation by lncRNAs results in tight lncRNA-target couplings

The determination of long non-coding RNA (lncRNA) function is a major challenge in RNA biology with applications to basic, translational, and medical research [1-7]. Our efforts to improve the accuracy of lncRNA-target inference identified lncRNAs that coordinately regulate both the transcriptional and post-transcriptional processing of their targets. Namely, these lncRNAs may regulate the transcription of their target and chaperone the resulting message until its translation, leading to tightly coupled lncRNA and target abundance. Our analysis suggested that hundreds of cancer genes are coordinately and tightly regulated by lncRNAs and that this unexplored regulatory paradigm may propagate the effects of non-coding alterations to effectively dysregulate gene expression programs. As a proof-of-principle we studied the regulation of DICER1 [8, 9]--a cancer gene that controls microRNA biogenesis--by the lncRNA ZFAS1, showing that ZFAS1 activates DICER1 transcription and blocks its post-transcriptional repression to phenomimic and regulate DICER1 and its target microRNAs.

bioinformatics↗

bioRxiv2022

Effective methods for bulk RNA-Seq deconvolution using scnRNA-Seq transcriptomes

RNA profiling technologies at single-cell resolutions, including single-cell and single-nuclei RNA sequencing (scRNA-Seq and snRNA-Seq, scnRNA-Seq for short), can help characterize the composition of tissues and reveal cells that influence key functions in both healthy and disease tissues. However, the use of these technologies is operationally challenging because of high costs and stringent sample-collection requirements. Computational deconvolution methods that infer the composition of bulk-profiled samples using scnRNA-Seq-characterized cell types can broaden scnRNA-Seq applications, but their effectiveness remains controversial. We produced the first systematic evaluation of deconvolution methods on datasets with either known or scnRNA-Seq-estimated compositions. Our analyses revealed biases that are common to scnRNA-Seq 10X Genomics assays and illustrated the importance of accurate and properly controlled data preprocessing and method selection and optimization. Moreover, our results suggested that concurrent RNA-Seq and scnRNA-Seq profiles can help improve the accuracy of both scnRNA-Seq preprocessing and the deconvolution methods that employ them. Indeed, our proposed method, Single-cell RNA Quantity Informed Deconvolution (SQUID), combined RNA-Seq transformation and dampened weighted least-squares deconvolution approaches to consistently outperform other methods in predicting the composition of cell mixtures and tissue samples. Furthermore, our analysis suggested that only SQUID could identify outcomes-predictive cancer cell subclones in pediatric acute myeloid leukemia and neuroblastoma datasets, suggesting that deconvolution accuracy improvements are vital to enabling its applications in the life sciences.

systems biology↗