Publications by authors named "Jasmine Sakr"
Article Synopsis
- Advances in RNA abundance quantification have been largely driven by high-throughput "short-read" technologies, but accurately quantifying full-length transcript isoforms has remained difficult.
- Long-read sequencing platforms offer the potential for better isoform quantification, but bioinformatic challenges arise from the complexity of isoforms and genetic variation.
- To address this, the study introduces 'lr-kallisto', a new tool that adapts existing RNA-seq quantification methods for long-read data, improving accuracy through exome capture.
Article Synopsis
- Facioscapulohumeral dystrophy (FSHD) is caused by the contraction of D4Z4 repeats on chromosome 4q, affecting gene regulation due to mutations that serve as disease modifiers.
- The condition is characterized by disruption of heterochromatin and abnormal expression of the DUX4 transcription factor, but understanding this process has been complicated by genetic variability in patient muscle cells.
- This study developed isogenic cell lines to show how mutations influence D4Z4 heterochromatin differently, stabilizing DUX4 activation and revealing how it contributes to FSHD through downstream targets.
The majority of mammalian genes encode multiple transcript isoforms that result from differential promoter use, changes in exonic splicing, and alternative 3' end choice. Detecting and quantifying transcript isoforms across tissues, cell types, and species has been extremely challenging because transcripts are much longer than the short reads normally used for RNA-seq. By contrast, long-read RNA-seq (LR-RNA-seq) gives the complete structure of most transcripts.
View Article and Find Full Text PDFBackground: The TREM2 R47H variant is one of the strongest genetic risk factors for late-onset Alzheimer's Disease (AD). Unfortunately, many current Trem2 mouse models are associated with cryptic mRNA splicing of the mutant allele that produces a confounding reduction in protein product. To overcome this issue, we developed the Trem2 (Normal Splice Site) mouse model in which the Trem2 allele is expressed at a similar level to the wild-type Trem2 allele without evidence of cryptic splicing products.
View Article and Find Full Text PDFWe report a strategy for the orthogonal conjugation of the vinyl nucleosides, 5-vinyluridine (5-VU) and 2-vinyladenosine (2-VA), via selective reactivity with maleimide and tris(2-carboxyethyl)phosphine (TCEP), respectively. The orthogonality was investigated using density functional theory (DFT) and confirmed by reactions with vinyl nucleosides. Further, these chemistries were used to modify RNA for fluorescent cell imaging.
View Article and Find Full Text PDFProfiling RNA expression in a cell-specific manner continues to be a grand challenge in biochemical research. Bioorthogonal nucleosides can be utilized to track RNA expression; however, these methods currently have limitations due to background and incorporation of analogs into undesired cells. Herein, we design and demonstrate that uracil phosphoribosyltransferase can be engineered to match 5-vinyluracil for cell-specific metabolic labeling of RNA with exceptional specificity and stringency.
View Article and Find Full Text PDFBackground: Evidence from anatomical, pharmacological, and genetic studies supports a role for the neuropeptide melanin concentrating hormone system in modulating emotional and cognitive functions. Genome-wide association studies revealed a potential association between the melanin concentrating hormone receptor (MCHR1) gene locus and schizophrenia, and the largest genome-wide association study conducted to date shows a credible genome-wide association.
Methods: We analyzed MCHR1 and pro-melanin concentrating hormone RNA-Seq expression in the prefrontal cortex in schizophrenia patients and healthy controls.