A5053317035- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Gene Regulatory Network Analysis
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Molecular Biology Techniques and Applications
- Advanced Multi-Objective Optimization Algorithms
- Probabilistic and Robust Engineering Design
- Cancer Genomics and Diagnostics
- Target Tracking and Data Fusion in Sensor Networks
- Bayesian Modeling and Causal Inference
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- Optimal Experimental Design Methods
- Control Systems and Identification
- Circular RNAs in diseases
- Image and Signal Denoising Methods
- Advanced Image Processing Techniques
- Distributed Sensor Networks and Detection Algorithms
- Sparse and Compressive Sensing Techniques
- Renal and related cancers
- RNA and protein synthesis mechanisms
- Blind Source Separation Techniques
- COVID-19 Clinical Research Studies
- Bioinformatics and Genomic Networks
Stanford University
2018-2025
Stratford University
2019-2024
Texas A&M University
2013-2019
Texas A&M University System
2017
McMaster University
2012
Early stages of deadly respiratory diseases including COVID-19 are challenging to elucidate in humans. Here, we define cellular tropism and transcriptomic effects SARS-CoV-2 virus by productively infecting healthy human lung tissue using scRNA-seq reconstruct the transcriptional program “infection pseudotime” for individual cell types. predominantly infected activated interstitial macrophages (IMs), which can accumulate thousands viral RNA molecules, taking over 60% transcriptome forming...
Of major interest to translational genomics is the intervention in gene regulatory networks (GRNs) affect cell behavior; particular, alter pathological phenotypes. Owing complexity of GRNs, accurate network inference practically challenging and GRN models often contain considerable amounts uncertainty. Considering cost time required for conducting biological experiments, it desirable have a systematic method prioritizing potential experiments so that an experiment can be chosen optimally...
The extent splicing is regulated at single-cell resolution has remained controversial due to both available data and methods interpret it. We apply the SpliZ, a new statistical approach, detect cell-type-specific in >110K cells from 12 human tissues. Using 10X Chromium for discovery, 9.1% of genes with computable SpliZ scores are cell-type-specifically spliced, including ubiquitously expressed MYL6 RPS24 . These results validated RNA FISH, PCR, Smart-seq2. analysis reveals 170 during...
In many contemporary engineering problems, model uncertainty is inherent because accurate system identification virtually impossible owing to complexity or lack of data on account availability, time, cost. The situation can be treated by assuming that the true belongs an class models. this context, intrinsically Bayesian robust (IBR) filter one optimal relative cost function (in classical sense) and prior distribution over sense). IBR filters have previously been found for both Wiener...
The extent to which gene fusions function as drivers of cancer remains a critical open question. Current algorithms do not sufficiently identify false-positive arising during library preparation, sequencing, and alignment. Here, we introduce Data-Enriched Efficient PrEcise STatistical fusion detection (DEEPEST), an algorithm that uses statistical modeling minimize false-positives while increasing the sensitivity detection. In 9,946 tumor RNA-sequencing datasets from Cancer Genome Atlas...
An accurate understanding of interactions among genes plays a major role in developing therapeutic intervention methods. Gene regulatory networks often contain significant amount uncertainty. The process prioritizing biological experiments to reduce the uncertainty gene is called experimental design. Under such strategy, with high priority are suggested be conducted first.The authors have already proposed an optimal design method based upon objective for modeling networks, as deriving...
Hormones mediate long-range cell communication and play vital roles in physiology, metabolism, health. Traditionally, endocrinologists have focused on one hormone or organ system at a time. Yet, signaling by its very nature connects cells of different organs involves crosstalk hormones. Here, we leverage the organism-wide single transcriptional atlas non-human primate, mouse lemur (Microcebus murinus), to systematically map source target for 84 classes This work uncovers...
ABSTRACT Spinal Muscular Atrophy (SMA) is caused by a deficiency of the Survival Motor Neuron (SMN) protein. Mutations in SMN disrupt mRNA splicing and translation, leading to maladaptive changes transcriptomes, proteomes, neuroinflammation, metabolism, which drive motor neuron degeneration SMA patients. Using Drosophila model, we found that systemic depletion Smn leads accumulation RNA:DNA hybrids (R-loops), increased DNA damage, dysregulation amino acids sugar metabolism activation innate...
Abstract Myriad mechanisms diversify the sequence content of eukaryotic transcripts at both DNA and RNA levels, leading to profound functional consequences. Examples this diversity include splicing V(D)J recombination. Currently, these are detected using fragmented bioinformatic tools that require predefining a form transcript diversification rely on alignment an incomplete reference genome, filtering out unaligned sequences, potentially crucial for novel discoveries. Here, we present...
Abstract Myriad mechanisms diversify the sequence content of eukaryotic transcripts at both DNA and RNA levels, leading to profound functional consequences. Examples this diversity include splicing V(D)J recombination. Currently, these are detected using fragmented bioinformatic tools that require predefining a form transcript diversification rely on alignment an incomplete reference genome, filtering out unaligned sequences, potentially crucial for novel discoveries. Here, we present...
In many practical filter design problems, the exact statistical information of underlying random processes is not available. One robust filtering approach in these situations to an intrinsically Bayesian that provides optimal solution relative prior distribution governing uncertainty class all possible joint process models. this context, Kalman has been recently introduced for case second-order statistics observation and noise state-space model are unknown. However, such a does utilize...
Precise splice junction calls are currently unavailable in scRNA-seq pipelines such as the 10x Chromium platform but critical for understanding single-cell biology. Here, we introduce SICILIAN, a new method that assigns statistical confidence to junctions from spliced aligner improve precision. SICILIAN is general can be applied bulk or data, has particular utility analysis due data's unique challenges and opportunities discovery. SICILIAN's precise detection achieves high accuracy on...
Abstract SPLASH is an unsupervised, reference-free, and unifying algorithm that discovers regulated sequence variation through statistical analysis of k -mer composition, subsuming many application-specific methods. Here, we introduce SPLASH2, a fast, scalable implementation based on efficient counting approach. SPLASH2 enables rapid massive datasets from wide range sequencing technologies biological contexts, delivering unparalleled scale speed. The unveils new biology (without tuning) in...
In systems biology, network models are often used to study interactions among cellular components, a salient aim being develop drugs and therapeutic mechanisms change the dynamical behavior of avoid undesirable phenotypes. Owing limited knowledge, model uncertainty is commonplace dynamics can be updated in different ways, thereby giving multiple dynamic trajectories, that is, uncertainty. this manuscript, we propose an experimental design method effectively reduce improve performance...
ABSTRACT Early stages of deadly respiratory diseases such as COVID-19 have been challenging to elucidate due lack an experimental system that recapitulates the cellular and structural complexity human lung while allowing precise control over disease initiation systematic interrogation molecular events at resolution. Here we show healthy slices cultured ex vivo can be productively infected with SARS-CoV-2, tropism virus its distinct dynamic effects on host cell gene expression determined by...
Abstract RNA processing, including splicing and alternative polyadenylation, is crucial to gene function regulation, but methods detect processing from single-cell sequencing data are limited by reliance on pre-existing annotations, peak calling heuristics, collapsing measurements cell type. We introduce ReadZS, an annotation-free statistical approach identify regulated in single cells. ReadZS discovers type-specific human lung conserved, developmentally mammalian spermatogenesis—including...
Abstract Trimethylguanosine synthase 1 (TGS1) is a highly conserved enzyme that converts the 5′-monomethylguanosine cap of small nuclear RNAs (snRNAs) to trimethylguanosine cap. Here, we show loss TGS1 in Caenorhabditis elegans, Drosophila melanogaster and Danio rerio results neurological phenotypes similar those caused by survival motor neuron (SMN) deficiency. Importantly, expression human ameliorates SMN-dependent both flies worms, revealing can partly counteract effects SMN HeLa cells...