Biomedical subjects

Ali Mortazavi

Publications and source records attributed to Ali Mortazavi.

6 recordsLinked to original sources

PubMed2026

Dogme: a nextflow pipeline for reprocessing nanopore RNA and DNA modifications.

MOTIVATION: Oxford Nanopore (ONT) sequencing allows for the direct detection of RNA and DNA modifications from unamplified nucleic acids, which is a significant advantage over other platforms. However, the rapid updates to ONT basecalling models and the evolving landscape of computational tools for modification detection bring about challenges for reproducible and standardized analyses. To address these challenges, we developed Dogme to automate basecalling, alignment, modification detection, and transcript quantification. Dogme automates the reprocessing of ONT POD5 files by integrating basecalling using Dorado, read mapping using minimap2 and subsequent analysis steps such as running modkit. The pipeline supports three major types of sequencing data-direct RNA (dRNA), complementary DNA (cDNA), and genomic DNA (gDNA). Dogme facilitates detection of diverse RNA modifications supported by Dorado such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), inosine, pseudouridine, 2'-O-methylation (Nm) and DNA methylation, while concurrently quantifying full-length transcript isoforms LR-Kallisto for transcript quantification for dRNA and cDNA. RESULTS: We applied Dogme to three separate mouse C2C12 myoblast replicates using direct RNA sequencing on MinION flow cells. We detected 96 603 m6A, 43 476 m5C, 8829 inosine, 10 055 pseudouridine, and 30 320 Nm sites in three biological replicates. The pipeline produced reproducible modification profiles and transcript expression levels across replicates, demonstrating its utility for integrative long-read transcriptomic and epigenomic analyses. AVAILABILITY AND IMPLEMENTATION: Dogme is implemented in Nextflow and is freely available under the MIT license at https://github.com/mortazavilab/dogme, with documentation provided for installation and usage.

RNA↗

PubMed2006

Comparative genomics modeling of the NRSF/REST repressor network: from single conserved sites to genome-wide repertoire.

We constructed and applied an open source informatic framework called Cistematic in an effort to predict the target gene repertoire for transcription factors with large binding sites. Cistematic uses two different evolutionary conservation-filtering algorithms in conjunction with several analysis modules. Beginning with a single conserved and biologically tested site for the neuronal repressor NRSF/REST, Cistematic generated a refined PSFM (position specific frequency matrix) based on conserved site occurrences in mouse, human, and dog genomes. Predictions from this model were validated by chromatin immunoprecipitation (ChIP) followed by quantitative PCR. The combination of transfection assays and ChIP enrichment data provided an objective basis for setting a threshold for membership and rank-ordering a final gene cohort model consisting of 842 high-confidence sites in the human genome associated with 733 genes. Statistically significant enrichment of NRSE-associated genes was found for neuron-specific Gene Ontology (GO) terms and neuronal mRNA expression profiles. A more extensive evolutionary survey showed that NRSE sites matching the PSFM model exist in roughly similar numbers in all fully sequenced vertebrate genomes but are notably absent from invertebrate and protochordate genomes, as is NRSF itself. Some NRSF/REST sites reside in repeats, which suggests a mechanism for both ancient and modern dispersal of NRSEs through vertebrate genomes. Multiple predicted sites are located near neuronal microRNA and splicing-factor genes, and these tested positive for NRSF/REST occupancy in vivo. The resulting network model integrates post-transcriptional and translational controllers, including candidate feedback loops on NRSF and its corepressor, CoREST.

Animals↗

PubMed2006

Mining gene expression data by interpreting principal components.

BACKGROUND: There are many methods for analyzing microarray data that group together genes having similar patterns of expression over all conditions tested. However, in many instances the biologically important goal is to identify relatively small sets of genes that share coherent expression across only some conditions, rather than all or most conditions as required in traditional clustering; e.g. genes that are highly up-regulated and/or down-regulated similarly across only a subset of conditions. Equally important is the need to learn which conditions are the decisive ones in forming such gene sets of interest, and how they relate to diverse conditional covariates, such as disease diagnosis or prognosis. RESULTS: We present a method for automatically identifying such candidate sets of biologically relevant genes using a combination of principal components analysis and information theoretic metrics. To enable easy use of our methods, we have developed a data analysis package that facilitates visualization and subsequent data mining of the independent sources of significant variation present in gene microarray expression datasets (or in any other similarly structured high-dimensional dataset). We applied these tools to two public datasets, and highlight sets of genes most affected by specific subsets of conditions (e.g. tissues, treatments, samples, etc.). Statistically significant associations for highlighted gene sets were shown via global analysis for Gene Ontology term enrichment. Together with covariate associations, the tool provides a basis for building testable hypotheses about the biological or experimental causes of observed variation. CONCLUSION: We provide an unsupervised data mining technique for diverse microarray expression datasets that is distinct from major methods now in routine use. In test uses, this method, based on publicly available gene annotations, appears to identify numerous sets of biologically relevant genes. It has proven especially valuable in instances where there are many diverse conditions (10's to hundreds of different tissues or cell types), a situation in which many clustering and ordering algorithms become problematic. This approach also shows promise in other topic domains such as multi-spectral imaging datasets.

Algorithms↗

PubMed2003

Percutaneous intervention for the treatment of hypoplastic aortoiliac syndrome.

Hypoplastic aortoiliac syndrome (HAIS) occurs in young women and is characterized by a small infrarenal aorta with a hypoplastic iliofemoral arterial system and advanced atherosclerotic disease. Of 304 aortoiliac interventions (AoI), 30 female patients (mean age, 50 +/- 5 years) had HAIS. HAIS patients were less likely to have coronary disease (33% vs. 88%; P < 0.0001) or diabetes (10% vs. 42%; P < 0.001) compared to their AoI counterparts. Twenty-three patients (73%) had hyperlipidemia with mean cholesterol of 287 +/- 42 mg/dl. Twenty-eight patients (93%) were successfully treated with AoI. The ankle/brachial indices improved from pre-AoI ABI of 0.55 +/- 0.1 to post-AoI ABI of 0.99 +/- 0.1. Complications included one groin hematoma and one case of thrombosis. Follow-up averaged 31 months (range, 3-91 months) with an early (less than 12 months) restenosis rate of 7% and late (greater than 12 months) restenosis of 21%. One patient (3%) required surgical revascularization for persistent symptoms. Percutaneous treatment of HAIS is an alternative to surgical revascularization with satisfactory long-term results.

Aged↗

PubMed2002

Successful treatment of aortic endograft thrombosis with rheolytic thrombectomy.

PURPOSE: To report the benefits of rheolytic thrombectomy for treating aortic endograft thrombosis. METHODS: Of 40 patients who received the Ancure bifurcated endograft to treat abdominal aortic aneurysm (AAA) during a 9-month period, 6 (15%) patients (6 men; mean age 62.6 years, range 53-77) developed thrombosis of the endograft at an average of 9 weeks (range 1-20 months). Five patients were taking aspirin, and 3 were on warfarin therapy for atrial fibrillation. Immediately after angiography, rheolytic thrombectomy was used to remove the thrombus, followed by adjunctive procedures to treat the underlying pathology. RESULTS: Causes were kinking or extrinsic compression of the graft limb in 5 cases and thrombosis of the surgical closure site in a common femoral artery. Mechanical thrombectomy was successful in restoring circulation in all cases; thrombolysis was used in 1. All 6 patients had additional stents placed in the graft limbs, re-establishing patency. There was no mortality or recurrent thrombosis in a follow-up that has extended to 26 months, but 1 patient required additional stenting for subsequent focal kinking of a graft limb above the previously implanted stent. CONCLUSIONS: Rheolytic thrombectomy can safely and effectively treat endograft thrombosis after endovascular AAA repair. Additional thrombolytic agents, angioplasty, and stenting may be needed to correct the underlying causes of the thrombosis. Prophylactic stenting of iliac limbs at the time of implantation in patients with complex anatomy may prevent thrombosis of unsupported bifurcated endografts.

Aged↗

PubMed2002

Rare chronic gastric volvulus associated with left atrial and mediastinal compression.

We report a case of chronic gastric volvulus associated with left atrial compression in a 75-year-old woman who presented with chest pain, shortness of breath, and hypotension after elective hemiarthroplasty of the left hip. The patient's medical history included a paraesophageal hernia and gastric volvulus diagnosed in 1997 but left untreated. The present diagnosis of gastric volvulus was made on the basis of a chest radiograph and subsequent computed tomography. Echocardiography showed the volvulus compressing the left atrium. Surgery to repair the defect was successful, and there were no operative or postoperative complications. A review of the world medical literature revealed that gastric volvulus is rarely reported to cause hemodynamic compromise or compression of the heart and mediastinal structures.

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