Digital Commons Network^™

Robust Statistical Methods For Microbiome Abundance Data, Yiming Shi

WUSM Theses and Dissertations – All Programs

Differential abundance analysis in microbiome studies aims to identify taxa whose abundance differs across biological or clinical conditions. The observed data are typically taxon-specific sequencing read counts, representing reads assigned to different taxa within each sample. These counts are indirect measurements of the underlying microbial abundance profile and are constrained by sample-specific library sizes. Microbiome count data are also typically sparse, overdispersed, and heteroscedastic. Together, these characteristics create substantial challenges for differential abundance analysis and make the results highly sensitive to normalization procedures, model specification, and the statistical methods used for inference.

Normalization defines the scale on which samples are …

Interplay Of Autophagy And Mtor Signaling On Amyloid-Beta, Samuel Wycoff

WUSM Theses and Dissertations – All Programs

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ), a process thought to result from an imbalance between Aβ production and clearance. Autophagy, a major intracellular degradation pathway regulated by the mechanistic target of rapamycin (mTOR), has emerged as a potential therapeutic target for restoring Aβ homeostasis, although its precise role in Aβ metabolism remains unclear. This study investigated how pharmacological modulation of autophagy and mTOR signaling influences Aβ levels in both in vitro and in vivo models.

Wild-type SH-SY5Y neuroblastoma cells were treated with a panel of autophagy-modulating compounds, and extracellular Aβ secretion was quantified alongside the …

Surveillance And Comparative Genomics Of Bacteria From Hospital And Human Reservoirs, Emily E. Benedict

WUSM Theses and Dissertations – All Programs

Bacteria are diverse and adaptable and, consequently, present in a wide variety of environments. They are capable of growing under intense pressures, including those brought on by the human immune system and disinfection strategies. To survive these pressures, bacteria develop resistances. Antimicrobial resistance, which occurs when a microbe is no longer responsive to the antibiotic intended to control it, is one such adaptation that presents an especially serious threat, as it limits treatment options for infections caused by antimicrobial resistant microbes. Similarly, the ability of bacteria to survive in environments subjected to heavy disinfection efforts, such as intensive care units …

Investigating The Ability Of Presequences To Influence Mitochondrial Protein Import, Youmian Yan

WUSM Theses and Dissertations – All Programs

Mitochondria are essential organelles housing over 1000 proteins, 99% of which are nuclear-encoded and synthesized in the cytosol. Most mitochondrial proteins are targeted by a positively charged sequence called the presequence, which lacks a common sequence motif and is poorly conserved across evolution. Accumulating evidence suggests that presequences encode meaningful information that influences mitochondrial protein uptake. For instance, multiple stress response models propose that stress sensing proteins contain “weak” presequences which allows them to monitor mitochondrial health. However, there is a lack of systematic examination about how presequences influence import kinetics and what constitutes presequence strength. These gaps in knowledge …

Investigating How Mycobacterium Tuberculosis Promotes Its Survival In Neutrophils, Ananda N. Rankin

WUSM Theses and Dissertations – All Programs

The World Health Organization estimates that one-fourth of the world’s population has been exposed to Mycobacterium tuberculosis (Mtb). However, only 10% of those exposed develop active tuberculosis (TB), whereas other individuals will contain the pathogen in a latent state or clear the infection. It is unknown what mechanisms govern the development of active TB, latent infection, or clearance of infection, which is a barrier to successful treatment. Neutrophils have been identified as the predominantly infected cell type in bronchoalveolar lavage fluid, resected necrotic lung tissue, and sputum of patients with active TB. Lung neutrophil infiltration is also significantly increased in …

Multiomic And Single-Cell Analysis Of Tumors And Their Immune Microenvironment For Personalized Cancer Therapy, Kartik Singhal

WUSM Theses and Dissertations – All Programs

Precision oncology aims to match cancer treatment to the biology of an individual patient’s tumor. However, tumors that share a diagnosis can differ in their molecular features, cellular composition, clinical course, and response to therapy, making it difficult to determine which treatment will benefit an individual patient. This dissertation integrates genomic, transcriptomic, and single-cell multiomic computational analysis to characterize tumors across their somatic alterations, transcriptional cell states, microenvironment, and the immune response they elicit.

The first study describes a rare case of donor-derived follicular lymphoma following kidney transplantation. Genomic profiling showed that the donor and recipient tumors shared 31 somatic …

Specific Effects Of Pulsed Field Ablation On The Cardiac Tissue, The Nervous System And The Conduction System In Experimental And Clinical Studies, Josselin Duchateau, Iwanari Kawamura, Gurukripa N Kowlgi, Elad Maor, Moritz Nies, Christian W Zemlin, Tomás García-Sánchez, Samuel J Asirvatham

2020-Current year OA Pubs

AIMS: Pulsed field ablation (PFA) has emerged as a novel ablation modality for the treatment of cardiac arrhythmias and has rapidly reshaped contemporary electrophysiology practice. This article provides a comprehensive analysis on the mechanisms underlying the specific effects of PFA on myocardial, neural tissue structures, and the cardiac conduction system, integrating biophysical principles with preclinical and clinical evidence relevant to contemporary electrophysiology practice.

METHODS AND RESULTS: This document provides an exhaustive mechanistic explanation for the preferential effects of PFA on myocardium and the limits of the 'tissue-selectivity' concept. The complex interplay between cellular and tissue-level biophysics, biological responses, and tissue …

Activity-Dependent Astrocytic Cholesterol Release Fine-Tunes Modes Of Synaptic Exo- And Endocytosis, Jongyun Myeong, Vitaly A Klyachko

2020-Current year OA Pubs

Cholesterol is essential for the organization of neurotransmitter release machinery, yet how it regulates the balance among different forms of synaptic exo- and endocytosis remains poorly understood. Moreover, which pre-synaptic processes rely on neuronal vs. astrocyte-derived cholesterol is unknown. Using nanoscale-precision imaging of single-vesicle release in hippocampal synapses, we demonstrate that astrocytic cholesterol is a critical determinant of both temporal and spatial aspects of presynaptic dynamics by differentially modulating the two main forms of synchronous release, univesicular (UVR) and multivesicular (MVR), effectively fine-tuning their balance. Moreover, astrocytic cholesterol determines the spatial distribution of vesicle release across the active zone and …

Study Of Blood Linear Rna Nominates Cd55 And Dld As Early-Stage Biomarkers For Parkinson's Disease, Aleksandra Beric, Sarp Sahin, Santiago Sanchez, Zining Yang, Ravindra Kumar, Isabel Alfradique-Dunham, Jessie Sanford, Daniel Western, Bridget Phillips, John P Budde, Richard J Perrin, Paul T Kotzbauer, Joel S Perlmutter, Scott A Norris, Carlos Cruchaga, Laura Ibanez

2020-Current year OA Pubs

Parkinson's disease (PD) is the second leading neurodegenerative disease, pathologically characterized by the accumulation of alpha-synuclein in the brain and the loss of dopaminergic neurons in the substantia nigra pars compacta. Despite the intensive efforts to identify diagnostic biomarkers for PD and nominating prospective candidates such as such as CSF α-synuclein seed amplification assay or α-/β-synuclein ratio, establishment of minimally invasive biomarkers remains the focus of PD research. We leveraged transcriptomic data from 4343 participants from four independent datasets to robustly identify PD-associated transcripts. Following the differential abundance analyses, we integrated our findings with several brain transcriptomic, CSF proteomic, plasma …

Metanet: A Supervised Ensemble Learning Framework For Reconstructing Direct And Functional Tissue-Specific Transcription Factor Networks, Wooseok J Jung, Sandeep Acharya, Daniel P Ruskin, Shu Liao, Vaha Akbary Moghaddam, Zolboo Erdenebaatar, Michael R Brent

2020-Current year OA Pubs

MOTIVATION: Reconstructing tissue-specific transcription factor (TF) networks remains challenging. TF-motif-based methods often lack functional validation, while expression-based methods struggle to distinguish direct binding from indirect regulation. Integration of diverse data types is necessary to accurately prioritize likely functional targets directly bound by TFs across human tissues.

RESULTS: We introduce METANet (Motif Expression TF Association Networks), a supervised ensemble learning framework that combines TF motifs, cis-regulatory element activity, and linear and nonlinear expression-derived features to predict TF binding. Applied to 36 human tissues, predicted METANet maps significantly outperform established methods in identifying direct, likely functional targets of TFs validated by ChIP-seq …

Sortscore: Sort-Seq Mave Scoring And Visualization Using Python, Caitlyn Chitwood, Emily Orr, Dustin Baldridge

2020-Current year OA Pubs

SUMMARY: A growing number of tools enable the analysis of large variant libraries produced by multiplexed assays of variant effects (MAVEs). Experiments using fluorescent reporters and fluorescence-activated cell sorting sequencing (FACS-seq or Sort-seq) can coarsely quantify a given variant's impact on phenotypes such as transcription activity. Existing bioinformatics tools for Sort-seq data broadly fall into two categories: methods that model a genotype-phenotype landscape to infer latent variant phenotypes, and methods that directly estimate individual variant scores from experimental binned counts. Within this second category, sortscore provides an activity score computed directly from observed counts without fitting a model, retaining the …

Spatial Bias In Quality Of Estimated Delivery Date Records In The Electronic Health Record, Abigail Lewis, Randi Foraker, Min Lian, Min Zhao, Inez Oh, Aditi Gupta, Antonina Frolova, Philip R O Payne

2020-Current year OA Pubs

OBJECTIVES: This study evaluates the quality of estimated delivery dates (EDD) captured in electronic health record (EHR) systems, focusing on identifying and quantifying bias in these estimates for patients seeking prenatal care.

MATERIALS AND METHODS: We measured spatial and racial biases in the completeness and concordance of EDDs recorded in the EHR for patients seeking prenatal care. Element presence and agreement were compared across the catchment area to identify spatial patterns of bias in EDD records.

RESULTS: We obtained 38 477 unique pregnancy episodes in the EHR representing 33 081 unique patients between 2018 and 2022. Clear spatial and racial …

A Deep-Learning Based Biomarker Of Systemic Cellular Senescence Burden To Predict Mortality And Health Outcomes, Shangshu Zhao, Chia-Ling Kuo, Eric J Lenze, Julie L Wetherell, Laura Haynes, Perla El-Ahmad, Richard Fortinsky, George Kuchel, Trevor Harris, Breno S Diniz

2020-Current year OA Pubs

The accumulation of senescent cells is a recognized hallmark of biological aging and is associated with the onset of multiple chronic medical conditions. Senescent cells exhibit a distinct secretory profile, known as the senescence-associated secretory phenotype (SASP), which can propagate cellular senescence to neighboring and distant tissues. Measuring SASP factors in blood serves as a practical proxy for cellular senescence burden and may help track disease states and intervention outcomes. We developed and validated a composite SASP Score by integrating large-scale population proteomics data with a semi-supervised deep learning framework. The analytical workflow included: (1) selection of biologically curated SASP …

Unveiling Functional-Metabolic Synergy In The Healthy Brain: Multivariate Integration Of Dynamic [18f]Fdg-Pet And Resting-State Fmri, Claudia Tarricone, Giulia Vallini, Giorgia Baron, Massimiliano Facca, Erica Silvestri, Tommaso Volpi, Andrei G Vlassenko, Manu S Goyal, Alessandra Bertoldo

2020-Current year OA Pubs

Despite accounting for only 2% of body weight, the human brain requires significant amounts of glucose, even at rest, underscoring the importance of functional-metabolic relationships. Previous studies revealed moderate associations between resting-state fMRI functional connectivity (FC) and local metabolism via [

High-Grade Astrocytoma With Piloid Features: A Clinical And Genomic Analysis Of Prognostic Factors Using A Large Cohort, Shuodan Zhang, Omar H Butt, Sonika Dahiya, Et Al.

2020-Current year OA Pubs

BACKGROUND: High-grade astrocytoma with piloid features (HGAP) is a recently defined tumor type that is not well understood. Prognostic factors of clinical outcomes are not well established.

METHODS: Methylation profiling was performed on tumor samples, many at the National Cancer Institute (NCI) Laboratory of Pathology, and others from publicly available sources. Methylation classifier scores of ≥0.90 to the HGAP class on the NCI-Bethesda classifier version 3 were included. Clinical features were collected from the medical record. Survival analyses were performed using the Kaplan-Meier and Cox-proportional hazards methods.

RESULTS: The cohort comprised 421 patients. There were high rates of ATRX alteration …

Comprehensive Evaluation Of At(N) Imaging Biomarkers For Predicting Cognitive Decline, Tom Earnest, Braden Yang, Deydeep Kothapalli, Aristeidis Sotiras, Alzheimer's Disease Neuroimaging Initiative

2020-Current year OA Pubs

INTRODUCTION: Few studies have investigated how different Alzheimer's disease biomarker definitions affect predictions of cognitive decline.

METHODS: We predicted cognitive decline using 42 biomarker definitions spanning amyloid beta, tau, and neurodegeneration in 383 ADNI participants with baseline neuroimaging and longitudinal cognitive assessments. We identified optimal predictors for each pathology and variable type (continuous, binary, non-binary categorical) using nested cross-validation. Models were compared against support vector machines (SVMs) incorporating brain-wide pathology. In a subsample, we compared imaging-based biomarkers with biofluids (cerebrospinal fluid and plasma).

RESULTS: We observed substantial variability in accuracy, even for measures of the same pathology. Tau biomarkers were …

Spatial Control Of Parathyroid Hormone Receptor-1 Signaling Dictates Ligand-Specific Biological Outcomes, Jakob Höppner, Harald Jüppner, Monica Reyes, Prem Swaroop Yadav, Dian Wang, Thomas Dean, Patrick Hanna, Roberto Civitelli, Asuka Inoue, Ernestina Schipani, Ignacio Portales-Castillo, Thomas J Gardella

2020-Current year OA Pubs

Parathyroid hormone receptor-1 (PTH1R) is a class B GPCR that regulates mineral ion homeostasis via parathyroid hormone (PTH) and skeletal development via parathyroid hormone-related peptide (PTHrP). While PTHrP signaling is thought to occur predominantly at the plasma membrane, PTH is considered to also signal from endosomes; however, the mechanisms that encode subcellular PTH1R actions, as well as the biological relevance of plasma membrane vs internalized PTH1R activation, remain unclear. Here, by examining the Eiken syndrome mutant R485X-PTH1R, in which C-tail truncation removes key βarrestin docking sites, we identified βarrestins as critical modulators of compartmentalized PTH1R signaling in response to endogenous …

The C3-C3ar Axis Modulates Trained Immunity In Alveolar Macrophages, Alexander P Earhart, Rafael Aponte Alburquerque, Marick Starick, Lorena Garnica, Ayse Naz Ozanturk, Rahul Kumar Maurya, Xiaobo Wu, Jeffrey Haspel, Hrishikesh S Kulkarni, Et Al.

2020-Current year OA Pubs

Complement protein C3 is crucial for immune responses in mucosal sites such as the lung, where it aids in microbe elimination, and enhances inflammation. While trained immunity - enhanced secondary responses of innate immune cells after prior exposure - is well-studied, the role of the complement system in trained immune responses remains unclear. We investigated the role of C3 in trained immunity and found that alveolar macrophage (AM)

Characterization Of An Open-Channel Structure And Lateral Conduction Pathway In The Cation-Selective Pentameric Ligand-Gated Ion Channel, Elic, Mark J Arcario, Elizabeth J Wu-Chen, Yuna Shim, Jérôme Hénin, Grace Brannigan, Wayland W L Cheng

2020-Current year OA Pubs

Open-channel structures of multiple pentameric ligand-gated ion channels (pLGICs) have been determined, including the prokaryotic model pLGIC, Erwinia ligand-gated ion channel (ELIC). For many of these structures, it remains uncertain whether they represent a physiologic open-channel state because the conditions used for structure determination do not match those of functional measurements in cell membranes. Here, MD simulation is used to examine the ion conduction properties of the ELIC open-channel structure, which was determined using a non-desensitizing mutant called ELIC5. Results from simulations show that the pore remains stably open on the microsecond timescale, but computational electrophysiology measurements demonstrate a large …

Isolated Perianal Fistulizing Crohn's Disease In Contemporary Clinical Practice: A Multicenter Ecco-Confer Cohort Study, Kumarini Basnayake, Parakkal Deepak, Sami Samaan, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Isolated perianal fistulizing Crohn's disease (IPFCD) is an uncommon presentation of Crohn's disease with an uncertain natural history. We aimed to characterize contemporary diagnostic strategies, management approaches, and long-term outcomes, including progression to luminal Crohn's disease.

METHODS: We conducted a retrospective multicenter cohort study across 25 centers within the ECCO-CONFER network. Adult patients with IPFCD and no evidence of luminal Crohn's disease at baseline were included. The primary outcome was progression to luminal Crohn's disease. Secondary outcomes included clinical and radiological fistula response and patterns of medical and surgical management. Time-to-event analyses were performed using Kaplan-Meier methods. …

Complementary Vertebrate Wac Models Exhibit Phenotypes Relevant To Desanto-Shinawi Syndrome, Kang-Han Lee, Marwan Shinawi, Et Al.

2020-Current year OA Pubs

Monogenic syndromes are associated with neurodevelopmental changes that result in cognitive impairments and neurobehavioral phenotypes, including autism and seizures. Limited studies and resources are available to make meaningful headway into the underlying molecular mechanisms that result in these symptoms. One such example is DeSanto-Shinawi Syndrome (DESSH), a rare disorder caused by pathogenic variants in the

Current State And Needs Of Clinical Laboratories In Selected Countries In Africa, Merih Tesfazghi, Anne E Tebo, Roa Harb, Anthony O Okorodudu, Lee Schroeder, Jeannette Guarner, Christine Bales, Jack Ladenson, Allison Targowski, Kerry Cosby, Olajumoke Oladipo

2020-Current year OA Pubs

The Africa Working Group, under the auspices of the Global Laboratory Quality Initiative of the Association for Diagnostics & Laboratory Medicine (ADLM), conducted several educational workshops in Africa to promote laboratory quality in the region. The challenges faced in maintaining quality in clinical laboratories in low-resource countries may differ from region to region and country to country. To better understand current gaps and inform our engagement with partners in Africa, a needs assessment survey was distributed to 1427 ADLM members in Africa and further disseminated through local partners, resulting in 121 responses from participants across 8 countries in the region. …

Irs: Iterative Reference Selection Improves Normalization Of Microbiome Sequencing Data, Yiming Shi, Lili Liu, Jun Chen, Kristine M Wylie, Todd N Wylie, Sung Hee Park, Ruiwen Zhou, Yin Cao, Stephanie A Fritz, Molly J Stout, Maria Cristina Vazquez Guillamet, Lei Liu

2020-Current year OA Pubs

Microbiome studies often seek to determine how the absolute abundances of individual taxa change across biological conditions, yet sequencing read counts are sample-specific scaled representations of those abundances. Because sampling depth can differ across samples, fold changes calculated directly from sequencing read counts do not generally represent absolute-abundance fold changes. Normalization methods attempt to account for these between-sample differences in sampling depth, but their accuracy depends on the reference used. In particular, total-sum scaling uses all taxa as the reference and can introduce compositional bias. Reference-based methods instead rely on taxa that are stable across conditions, but contamination of the …

The Impact Of Global Imbalance On Pelvic Fixation Failure: A Single Institution Matched Case-Control Study, Karan Joseph, Samuel Vogl, Jeffrey T Galla, Alexander T Yahanda, Vivek P Gupta, Salim Yakdan, Miguel A Ruiz-Cardozo, Benjamin Plog, Tim Bui, Noah D Poulin, Sundeep Chakladar, Francisco Narro-Garcia, Jason Ng, Matthew Wang, Braeden Benedict, Samuel Brehm, Hana Hallak, Karma Barot, Nicholas Pallotta, Munish C Gupta, Brian J Neuman, Jacob K Greenberg, Wilson Z Ray, Camilo A Molina

2020-Current year OA Pubs

Study DesignRetrospective matched case-control study.ObjectivesPelvic fixation failure (PFF) is a rare, underrecognized mechanical complication from surgical management of adult spinal deformity (ASD). Studies show that residual postoperative malalignment may increase mechanical stress on pelvic instrumentation, but the role of global radiographic parameters in predicting PFF remains poorly defined. Our study aims to identify radiographic predictors of PFF and evaluate the time-dependent relationship between residual deformity and PFF rates.MethodsThis was a single-center, retrospective, matched case-control study of ASD patients who underwent pelvic fixation from 2016-2024 and had >1-year postoperative follow-up. PFF was defined as any reoperation for pelvic screw or rod …

Spinal Cord Imaging For Multiple Sclerosis: Advances, Priorities, And Opportunities, Cornelia Laule, Matthew R Brier, Et Al.

2020-Current year OA Pubs

The spinal cord plays a central role in the pathophysiology and clinical manifestations of multiple sclerosis (MS), yet remains under-studied compared with the brain. This review summarizes key insights from the 2025 North American Imaging in MS Spinal Cord Imaging Workshop, highlighting recent advances, ongoing challenges, and future opportunities in MS spinal cord imaging. We review pathological studies and outline the clinical relevance of spinal cord lesions and atrophy for diagnosis, prognosis, and disease monitoring, highlighting emerging biomarkers of progression independent of relapse activity. Correlations between magnetic resonance imaging, histopathology, and clinical outcomes support the validation and translational potential of …

Perioperative Depression And Anxiety Care In Older Patients: A Randomized Clinical Trial, Joanna Abraham, Katherine J Holzer, Simon Haroutounian, Bethany Pennington, Ana Baumann, Ryan Calfee, Theresa Cordner, Kenneth E Freedland, Thomas Kannampallil, Benjamin Kozower, Emily Lenard, J Philip Miller, Mary Politi, Michael Yingling, Michael S Avidan, Eric J Lenze

2020-Current year OA Pubs

IMPORTANCE: Depression and anxiety are common among older adults undergoing surgery and are associated with adverse postoperative outcomes. However, effective tailored perioperative mental health interventions are lacking.

OBJECTIVE: To evaluate a perioperative intervention to optimize mental health.

DESIGN, SETTING, AND PARTICIPANTS: A single-blind, hybrid, type 1, effectiveness-implementation randomized clinical trial was conducted (November 1, 2022, to March 31, 2025), with 3-month postoperative follow-up, at a US academic and community practice hospital network. Participants were 60 years or older; scheduled for cardiac, oncologic, or orthopedic surgery; and had clinically meaningful symptoms of depression and/or anxiety based on the Patient Health Questionnaire-Anxiety …

Pda (Privacy-Preserving Distributed Algorithms) In Action: Ten Principles For High-Quality Multi-Site Clinical Evidence Generation, Yong Chen, Chongliang Luo, Et Al.

2020-Current year OA Pubs

BACKGROUND: Distributed Research Networks (DRNs) offer significant opportunities for collaborative multi-site research and have significantly advanced healthcare research based on clinical observational data. However, generating high-quality real-world evidence using fit-for-use data from multi-site studies faces important challenges, including biases associated with various types of heterogeneity within and across sites and data sharing difficulties. Over the last 10 years, Privacy-Preserving Distributed Algorithms (PDA) have been developed and utilized in numerous national and international real-world studies spanning diverse domains, from comparative effectiveness research, target trial emulation, to healthcare delivery, policy evaluation, and system performance assessment. Despite these advances, there remains a lack …

Dnl343 And Disease Progression In Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial, Sabrina Paganoni, Timothy Miller, Et Al.

2020-Current year OA Pubs

IMPORTANCE: DNL343 is a brain-penetrant small molecule that acts as an activator of eukaryotic translation initiation factor 2B (eIF2b), designed to inhibit the integrated stress response. A prior phase 1B trial of DNL343 in amyotrophic lateral sclerosis (ALS) provided evidence of a favorable safety profile, central nervous system penetrance, and target engagement based on integrated stress response biomarkers in blood and cerebrospinal fluid.

OBJECTIVES: To evaluate the safety and efficacy of a 200-mg formulation of DNL343 given once daily in individuals living with ALS.

DESIGN, SETTING, AND PARTICIPANTS: DNL343 was evaluated as a regimen of the HEALEY ALS Platform Trial, …

Parent-Child Neural Dynamics During A Stressful Task: Probing Associations With Temperament And Anxiety, Joscelin Rocha-Hidalgo, Harmony Nguyen, Dakota Reis, Denny Schaedig, Kahlil I Thompson, Susan B Perlman, Koraly E Pérez-Edgar

2020-Current year OA Pubs

Dynamic social interactions between parents and children can contribute to anxiety risk, amplifying shared genetic risk. Research has focused on observed behaviors to explain intergenerational transmission. Neural synchrony may contribute as a biological conduit for behavioral transmission of risk. We examined 109 parent-child dyads (

Gamclust: Identification Of Regulated Metabolic Modules In Bulk, Single Cell And Spatial Gene Expression Data, Anastasiia Gainullina, Evgeniia Chikina, Maxim N Artyomov, Alexey Sergushichev

2020-Current year OA Pubs

MOTIVATION: Metabolism operates as a highly interconnected biochemical network, and its regulation emerges from coordinated changes across many reactions and metabolites. The integration of gene expression profiling data with organism-scale metabolic networks has proven to be a valuable tool for understanding cellular metabolic regulation. However, the increasing complexity of profiling technologies and experimental designs requires the development of specialized tools.

RESULTS: Here, we present GAMclust, an R package implementing and extending the previously published GAM-clustering pipeline for identifying transcriptionally regulated metabolic modules in complex gene expression datasets. GAMclust supports bulk, single-cell, and spatial gene expression profiling. It includes built-in KEGG …