Biology subjects

Momin, Z.

Publications and source records attributed to Momin, Z..

9 recordsLinked to original sources

bioRxiv2026

Multi-Omics Study of Ancestry in Adults with Intracranial Cancers Glioma (MOSAIC)

BackgroundMost genomic studies of adult-type diffuse gliomas have focused on predominantly European ancestry populations, limiting the generalizability of molecular classifications and precision medicine approaches. We assembled a multi-institutional glioma cohort of diverse patients to investigate how germline ancestry, molecular subtypes, and mutational processes shape tumor biology and clinical outcomes. MethodsWe analyzed 1,102 adults with WHO 2021-classified diffuse gliomas (IDH-mutant, 1p/19q-codeleted oligodendroglioma; IDH-mutant astrocytoma; IDH-wildtype glioma) from seven U.S. institutions. Whole-exome sequencing (WES) of FFPE tumors identified somatic alterations and COSMIC SBS v3.2 mutational signatures. Genetic ancestry was estimated from WES using 1000 Genomes reference populations. Overall survival was assessed using Kaplan-Meier and multivariable models. ResultsThe cohort included 66.9% European (EUR), 21.1% Admixed American/Hispanic (AMR), 10.3% Admixed African (AFR), and 1.6% Asian (AS) ancestry. Survival followed expected molecular hierarchy (median overall survival: oligodendroglioma 15.7 years, astrocytoma 10.6 years, IDH-wildtype glioma 1.9 years). Within oligodendroglioma, AMR patients showed improved survival versus EUR (HR 0.67, 95% CI 0.48-0.94; p=0.011), with similar trends across subtypes. Somatic profiling confirmed canonical subtype-defining alterations and revealed higher ATRX alterations in AFR and AMR IDH-wildtype tumors compared with EUR. ATRX alterations were associated with improved survival only in AFR (p=0.003). Mutational signature analysis identified subtype-specific signatures, including therapy-associated signatures. Chemotherapy-related signatures were more frequent in EUR and AMR than in AFR. ConclusionsThis ancestrally diverse glioma cohort confirms established molecular classifications and identifies ancestry-associated differences in survival, somatic alterations, and mutational processes, indicating the critical need for broad representation to inform precision neuro-oncology. Key PointsO_LIA multi-institutional glioma cohort validates subtype and survival patterns across ancestries. C_LIO_LITherapy-associated mutational signatures differ by ancestry, suggesting distinct treatment-related mutational processes. C_LIO_LIAdmixed American patients show improved survival, particularly in oligodendroglioma. C_LI Importance of the StudyMost genomic studies of adult-type diffuse glioma have focused on populations of predominantly European ancestry which limits the ability to examine variation in tumor biology and clinical outcomes across populations. In this study, we assembled one of the largest ancestrally diverse cohorts of molecularly characterized adult diffuse gliomas, integrating germline ancestry inference with tumor whole-exome sequencing and mutational signature analysis. We confirm that established molecular classifications and survival hierarchies remain robust across ancestry groups. However, we also identified ancestry-associated differences in survival within specific tumor subtypes, higher ATRX alteration frequencies in African American and admixed American patients with IDH-wildtype tumors, and variation in therapy-associated mutational signatures across ancestry groups. These findings highlight the importance of incorporating population differences into genomic studies of glioma and provide a resource for future multi-ancestry investigations of glioma risk, tumor evolution, and treatment response, ultimately supporting more inclusive precision neuro-oncology.

bioinformatics↗

bioRxiv2026

Multi-Omics Characterization of Human Molecular Responses to Spaceflight Across Two Independent Missions

Human spaceflight has historically been led by government agencies, but the emergence of commercial organizations is enabling broader participation and new research opportunities. In this study, we present a comprehensive molecular characterization of early human responses to spaceflight, leveraging multi-omics data across the first three weeks of two commercial missions. Biospecimens from six individuals, four from the Axiom 2 mission (10 days) and two from Axiom 3 (21 days), were analyzed using single-cell and bulk RNA sequencing, alongside proteomic profiling. Individual and integrative analyses of these datasets reveal systemic changes in cell types, transcripts, and proteins related to immune regulation, osteoclast differentiation, NF-{kappa}B signaling, and blood homeostasis pathways. Importantly, several of the detected pathways align with physiological patterns observed in longer-duration missions. This work establishes a foundational resource for understanding early adaptation to spaceflight at the cellular and molecular levels, providing insights to reduce future space-travel health risks. HighlightsO_LIFirst integrated multi-omics analysis using single-cell, bulk RNA sequencing and proteomic profiling of early human spaceflight responses across two commercial missions (Ax-2 and Ax-3). C_LIO_LIDistinct PBMC clustering was observed across Ax-2 and Ax-3, and post-flight samples. It showed fewer monocytes, dendritic cells, and megakaryocytes with increased naive CD4 and cytotoxic T cells. C_LIO_LIMulti-omics integration identifies shared biological signatures, including osteoclast differentiation, metabolic stress, and coagulation changes. C_LIO_LIThese findings lay the foundation for developing countermeasures to protect immune, skeletal, and vascular health during spaceflight. C_LI

molecular biology↗

bioRxiv2026

Microbial Dynamics Across Commercial Spaceflights of Varying Duration

SummarySpaceflight introduces environmental stressors that can alter human microbiomes and immune responses. We analyzed 259 biospecimens from six astronauts across two commercial ISS missions: Axiom 2 (10-day mission) and Axiom 3 (21-day mission). Samples included saliva, stool, urine, and body swabs from 10 anatomical sites, profiled via 16S ribosomal RNA (rRNA) gene sequencing. Gut and oral microbiomes remained stable, while skin-associated communities exhibited transient diversity shifts post-flight. Taxonomic analysis revealed individual and site-specific patterns as well as a possible microbial acquisition from the ISS/space-flight environment and microbiome exclusivity. Cytokine profiling from single cell data indicated immune activation, with IL-32 and IL-16 elevated in Axiom 2 and Axiom 3, coinciding with microbial changes. These findings provide an integrated view of microbiome individuality, exclusivity and immune dynamics during two short-duration commercial spaceflights of three weeks, informing strategies for crew health on future long-duration missions.

microbiology↗

bioRxiv2025

Pre-Sequencing Assessment of RNA-Seq Library Quality Using Real-Time qPCR

RNA sequencing (RNA-Seq) is an essential sequencing assay for studying transcriptome profiling. Ribosomal RNA (rRNA) comprises more than 80 - 90% of total cellular RNA, efficient rRNA removal is essential for accurately capturing the transcriptome, particularly to sequence low-abundance mRNAs. Inefficient rRNA removal during library preparation can result from variations in sample quality, preparation methods and handling. Estimating rRNA content in RNA-Seq libraries pre-sequencing is therefore challenging due to the absence of a reliable and cost-effective assessment method. This study addresses the issue by introducing a scalable qPCR-based assay targeting 18S rRNA to evaluate rRNA depletion efficiency pre-sequencing. qPCR efficiency was optimized using serial dilutions of Universal Human Reference (UHR) control and Ct thresholds were established using pilot data from 644 libraries. Following this optimization, analysis of 1,748 Total RNA-Seq libraries and 445 Poly A+ two widely used RNA-Seq library methods, demonstrated a strong correlation between 18S rRNA qPCR results and post-sequencing rRNA rates. This assay was also used to evaluate the performance of Oligo dT beads from four different vendors to enrich mRNA. This 18S rRNA qPCR assay is a cost-effective, scalable approach for reliably predicting rRNA read percentage in RNA-Seq libraries pre-sequencing. Method SummaryThe 18S rRNA-specific qPCR assay is a cost-effective method for evaluating rRNA depletion efficiency in RNA-Seq libraries prior to sequencing by targeting the 18S ribosomal RNA. qPCR efficiency was optimized, and Ct thresholds were set from pilot data and validated across 1,748 Total RNA and 445 Poly A+ RNA-Seq libraries. A Ct threshold of [≥]16 for Total RNA and Ct 13-14 or greater for Poly A+ libraries demonstrates a strong correlation between qPCR results and post-sequencing rRNA read percentages. The assay enables early identification of poorly depleted samples, reducing unnecessary sequencing costs. Additionally, the method was employed to benchmark oligo-dT beads from four vendors, showing its utility in evaluating RNA-seq library preparation kits. This scalable approach supports quality control in both research and high-throughput sequencing environments.

molecular biology↗

bioRxiv2024

Complete Genomic Characterization of Global Pathogens, Respiratory Syncytial Virus (RSV), and Human Norovirus (HuNoV) Using Probe-based Capture Enrichment.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children worldwide, while human noroviruses (HuNoV) are a leading cause of epidemic and sporadic acute gastroenteritis. Generating full-length genome sequences for these viruses is crucial for understanding viral diversity and tracking emerging variants. However, obtaining high-quality sequencing data is often challenging due to viral strain variability, quality, and low titers. Here, we present a set of comprehensive oligonucleotide probe sets designed from 1,570 RSV and 1,376 HuNoV isolate sequences in GenBank. Using these probe sets and a capture enrichment sequencing workflow, 85 RSV positive nasal swab samples and 55 (49 stool and six human intestinal enteroids) HuNoV positive samples encompassing major subtypes and genotypes were characterized. The Ct values of these samples ranged from 17.0-29.9 for RSV, and from 20.2-34.8 for HuNoV, with some HuNoV having below the detection limit. The mean percentage of post-processing reads mapped to viral genomes was 85.1% for RSV and 40.8% for HuNoV post-capture, compared to 0.08% and 1.15% in pre-capture libraries, respectively. Full-length genomes were>99% complete in all RSV positive samples and >96% complete in 47/55 HuNoV positive samples--a significant improvement over genome recovery from pre-capture libraries. RSV transcriptome (subgenomic mRNAs) sequences were also characterized from this data. Probe-based capture enrichment offers a comprehensive approach for RSV and HuNoV genome sequencing and monitoring emerging variants. IMPORTANCERespiratory syncytial virus (RSV) and human noroviruses (HuNoV) are NIAID category C and category B priority pathogens, respectively, that inflict significant health consequences on children, adults, immunocompromised patients, and the elderly. Due to the high strain diversity of RSV and HuNoV genomes, obtaining complete genomes to monitor viral evolution and pathogenesis is challenging. In this paper, we present the design, optimization, and benchmarking of a comprehensive oligonucleotide target capture method for these pathogens. All 85 RSV samples and 49/55 HuNoV samples were patient-derived with six human intestinal enteroids. The methodology described here results has a higher success rate in obtaining full-length RSV and HuNoV genomes, enhancing the efficiency of studying these viruses and mutations directly from patient-derived samples.

molecular biology↗

bioRxiv2020

Oligonucleotide Capture Sequencing of the SARS-CoV-2 Genome and Subgenomic Fragments from COVID-19 Individuals

The newly emerged and rapidly spreading SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). To facilitate a deeper understanding of the viral biology we developed a capture sequencing methodology to generate SARS-CoV-2 genomic and transcriptome sequences from infected patients. We utilized an oligonucleotide probe-set representing the full-length genome to obtain both genomic and transcriptome (subgenomic open reading frames [ORFs]) sequences from 45 SARS-CoV-2 clinical samples with varying viral titers. For samples with higher viral loads (cycle threshold value under 33, based on the CDC qPCR assay) complete genomes were generated. Analysis of junction reads revealed regions of differential transcriptional activity and provided evidence of expression of ORF10. Heterogeneous allelic frequencies along the 20kb ORF1ab gene suggested the presence of a defective interfering viral RNA species subpopulation in one sample. The associated workflow is straightforward, and hybridization-based capture offers an effective and scalable approach for sequencing SARS-CoV-2 from patient samples.

genomics↗

bioRxiv2020

Oligonucleotide capture sequencing of the SARS-CoV-2 genome and subgenomic fragments from COVID-19 individuals

microbiology↗

bioRxiv2020

Preventive efficacy of a tenofovir alafenamide fumarate nanofluidic implant in SHIV-challenged nonhuman primates

Pre-exposure prophylaxis (PrEP) using antiretroviral oral drugs is effective at preventing HIV transmission when individuals adhere to the dosing regimen. Tenofovir alafenamide (TAF) is a potent antiretroviral drug, with numerous long-acting (LA) delivery systems under development to improve PrEP adherence. However, none has undergone preventive efficacy assessment. Here we show that LA TAF using a novel subcutaneous nanofluidic implant (nTAF) confers partial protection from HIV transmission. We demonstrate that sustained subcutaneous delivery through nTAF in rhesus macaques maintained tenofovir diphosphate concentration at a median of 390.00 fmol/106 peripheral blood mononuclear cells, 9 times above clinically protective levels. In a non-blinded, placebo-controlled rhesus macaque study with repeated low-dose rectal SHIVSF162P3 challenge, the nTAF cohort had a 62.50% reduction (95% CI: 1.72% to 85.69%; p=0.068) in risk of infection per exposure compared to the control. Our finding mirrors that of tenofovir disoproxil fumarate (TDF) monotherapy, where 60.00% protective efficacy was observed in macaques, and clinically, 67.00% reduction in risk with 86.00% preventive efficacy in individuals with detectable drug in the plasma. Overall, our nanofluidic technology shows potential as a subcutaneous delivery platform for long-term PrEP and provides insights for clinical implementation of LA TAF for HIV prevention.

bioengineering↗

bioRxiv2019

Genomic landscape of 261 childhood cancer patient-derived xenograft models

Accelerating cures for children with cancer remains an immediate challenge due to extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs) from high-risk childhood cancers, many refractory to current standard-of-care treatments. Here, we genomically characterize 261 PDX models from 29 unique pediatric cancer malignancies and demonstrate faithful recapitulation of histologies, subtypes, and refine our understanding of relapsed disease. Expression and mutational signatures are used to classify tumors for TP53 and NF1 inactivation, as well as impaired DNA repair. We anticipate that these data will serve as a resource for pediatric oncology drug development and guide rational clinical trial design for children with cancer.\n\nHighlightsO_LIMultiplatform genomic analysis defines landscape of 261 pediatric cancer patient derived xenograft (PDX) models\nC_LIO_LIPediatric patient derived xenografts faithfully recapitulate relapsed disease\nC_LIO_LIInferred TP53 pathway inactivation correlates with pediatric cancer copy number burden\nC_LIO_LISomatic mutational signatures predict impaired DNA repair across multiple histologies\nC_LI

genomics↗