Maintenance of neuronal TDP-43 expression requires axonal lysosome transport DOI Creative Commons
Veronica H. Ryan,

Sydney Lawton,

Joel F. Reyes

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Abstract TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate in neurons are not well understood. We generated Halo-TDP-43 knock-in iPSC line performed genome-wide CRISPR interference FACS-based screen to identify modifiers levels neurons. A meta-analysis our publicly available screens identified both specific hits present multiple screens, latter likely responsible for generic protein level maintenance. BORC, complex required anterograde lysosome transport, as modifier protein, mRNA, BORC loss led longer half-life other proteins, suggesting location is proper turnover. As such, function crucial maintaining

Language: Английский

Transforming Clinical Research: The Power of High-Throughput Omics Integration DOI Creative Commons
Rui Vitorino

Proteomes, Journal Year: 2024, Volume and Issue: 12(3), P. 25 - 25

Published: Sept. 6, 2024

High-throughput omics technologies have dramatically changed biological research, providing unprecedented insights into the complexity of living systems. This review presents a comprehensive examination current landscape high-throughput pipelines, covering key technologies, data integration techniques and their diverse applications. It looks at advances in next-generation sequencing, mass spectrometry microarray platforms highlights contribution to volume precision. In addition, this critical role bioinformatics tools statistical methods managing large datasets generated by these technologies. By integrating multi-omics data, researchers can gain holistic understanding systems, leading identification new biomarkers therapeutic targets, particularly complex diseases such as cancer. The also electronic health records (EHRs) potential for cloud computing big analytics improve storage, analysis sharing. Despite significant advances, there are still challenges complexity, technical limitations ethical issues. Future directions include development more sophisticated computational application advanced machine learning techniques, which addressing heterogeneity datasets. aims serve valuable resource practitioners, highlighting transformative advancing personalized medicine improving clinical outcomes.

Language: Английский

Citations

19
Mass Spectrometry Advancements and Applications for Biomarker Discovery, Diagnostic Innovations, and Personalized Medicine DOI Open Access

Ahrum Son,

Woojin Kim, Jongham Park

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9880 - 9880

Published: Sept. 12, 2024

Mass spectrometry (MS) has revolutionized clinical chemistry, offering unparalleled capabilities for biomolecule analysis. This review explores the growing significance of mass (MS), particularly when coupled with liquid chromatography (LC), in identifying disease biomarkers and quantifying biomolecules diagnostic prognostic purposes. The unique advantages MS accurately diverse molecules have positioned it as a cornerstone personalized-medicine advancement. MS-based technologies transformed precision medicine, enabling comprehensive understanding mechanisms patient-specific treatment responses. LC-MS shown exceptional utility analyzing complex biological matrices, while high-resolution expanded analytical capabilities, allowing detection low-abundance elucidation pathways. integration other techniques, such ion mobility spectrometry, opened new avenues biomarker discovery validation. As we progress toward will be crucial addressing challenges individualized patient care, driving innovations diagnosis, prognosis, strategies.

Language: Английский

Citations

10
Computational tools and algorithms for ion mobility spectrometry‐mass spectrometry DOI Creative Commons
Dylan H. Ross, Harsh Bhotika, Xueyun Zheng

et al.

PROTEOMICS, Journal Year: 2024, Volume and Issue: 24(12-13)

Published: March 4, 2024

Abstract Ion mobility spectrometry‐mass spectrometry (IMS‐MS or IM‐MS) is a powerful analytical technique that combines the gas‐phase separation capabilities of IM with identification and quantification MS. IM‐MS can differentiate molecules indistinguishable masses but different structures (e.g., isomers, isobars, molecular classes, contaminant ions). The importance this reflected by staged increase in number applications for characterization across variety fields, from MS‐based omics (proteomics, metabolomics, lipidomics, etc.) to structural glycans, organic matter, proteins, macromolecular complexes. With increasing application there pressing need effective accessible computational tools. This article presents an overview most recent free open‐source software tools specifically tailored analysis interpretation data derived instrumentation. review enumerates these outlines their main algorithmic approaches, while highlighting representative fields. Finally, discussion current limitations expectable improvements presented.

Language: Английский

Citations

9
Multiomics Evaluation of Human iPSCs and iPSC-Derived Neurons DOI
Gwang Bin Lee, Wan Nur Atiqah binti Mazli, Ling Hao

et al.

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(8), P. 3149 - 3160

Published: Feb. 28, 2024

Human induced pluripotent stem cells (iPSCs) can be differentiated into neurons, providing living human neurons to model brain diseases. However, it is unclear how different types of molecules work together regulate cell and neuron biology in healthy disease states. In this study, we conducted integrated proteomics, lipidomics, metabolomics analyses with confident identification, accurate quantification, reproducible measurements compare the molecular profiles iPSCs iPSC-derived neurons. Proteins, lipids, metabolites related mitosis, DNA replication, pluripotency, glycosphingolipids, energy metabolism were highly enriched iPSCs, whereas synaptic proteins, neurotransmitters, polyunsaturated fatty acids, cardiolipins, axon guidance pathways Mutations GRN gene lead deficiency progranulin (PGRN) protein, which has been associated various neurodegenerative Using multiomics platform, evaluated impact PGRN on at whole-cell level. Proteomics, implicated PGRN's roles neuroinflammation, purine metabolism, neurite outgrowth, revealing commonly altered projection, dysfunction, metabolism. Multiomics data sets also pointed toward same hypothesis that seem more susceptible loss compared consistent neurological symptoms cognitive impairment from patients carrying inherited mutations.

Language: Английский

Citations

6
MassDash: A Web-Based Dashboard for Data-Independent Acquisition Mass Spectrometry Visualization DOI
Justin Sing, Joshua Charkow, Mohammed AlHigaylan

et al.

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(6), P. 2306 - 2314

Published: April 29, 2024

With the increased usage and diversity of methods instruments being applied to analyze Data-Independent Acquisition (DIA) data, visualization is becoming increasingly important validate automated software results. Here we present MassDash, a cross-platform DIA mass spectrometry validation for comparing features results across popular tools. MassDash provides web-based interface Python package interactive feature visualizations summary report plots multiple detection tools, including OpenSwath, DIA-NN, dreamDIA. Furthermore, processes peptides on fly, enabling dozens runs simultaneously personal computer. supports various multidimensional retention time, ion mobility, m/z, intensity, providing additional insights into data. The modular framework easily extendable, rapid algorithm development novel peak-picker techniques, such as deep-learning-based approaches refinement existing open-source under BSD 3-Clause license freely available at https://github.com/Roestlab/massdash, demo version can be accessed https://massdash.streamlit.app.

Language: Английский

Citations

5
Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics DOI Creative Commons
Sudipa Maity, Yuanyu Huang, Mitchell D. Kilgore

et al.

Clinical Proteomics, Journal Year: 2024, Volume and Issue: 21(1)

Published: May 12, 2024

Abstract Background Traumatic brain injury (TBI) often results in diverse molecular responses, challenging traditional proteomic studies that measure average changes at tissue levels and fail to capture the complexity heterogeneity of affected tissues. Spatial proteomics offers a solution by providing insights into sub-region-specific alterations within This study focuses on hippocampal sub-regions, analyzing expression profiles mice acute (1 day) subacute (7 days) phases post-TBI understand subregion-specific vulnerabilities long-term consequences. Methods Three brains were collected from each group, including Sham, 1-day 7-day post-TBI. Hippocampal subregions extracted using Laser Microdissection (LMD) subsequently analyzed label-free quantitative proteomics. Results The spatial analysis reveals region-specific protein abundance changes, highlighting elevation FN1, LGALS3BP, HP, MUG-1 stratum moleculare (SM), suggesting potential immune cell enrichment Notably, established markers chronic traumatic encephalopathy, IGHM B2M, exhibit specific upregulation dentate gyrus bottom (DG2) independent direct mechanical injury. Metabolic pathway identifies disturbances glucose lipid metabolism, coupled with activated cholesterol synthesis pathways enriched SM 7-Day deeper DG1 DG2 role neurogenesis onset recovery. Coordinated activation neuroglia microtubule dynamics suggest recovery mechanisms less regions. Cluster revealed variations post-TBI, indicative dysregulated neuronal plasticity further predisposition neurological disorders. TBI-induced (MUG-1, PZP, GFAP, TJP, STAT-1, CD44) across sub-regions indicates shared responses links demonstrated proteins both or either time-points exclusively subregion (ELAVL2, CLIC1 PL, CD44 SM, SHOC2, LGALS3 DG). Conclusions Utilizing advanced techniques, unveils dynamic distinct It uncovers processes, recovery-related contribute our understanding TBI’s consequences provides valuable for biomarker discovery therapeutic targets.

Language: Английский

Citations

4
Maintenance of neuronal TDP-43 expression requires axonal lysosome transport DOI Open Access
Veronica H. Ryan,

Sydney Lawton,

Joel F. Reyes

et al.

Published: Jan. 6, 2025

TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate in neurons are not well understood. We generated Halo-TDP-43 knock-in iPSC line performed genome-wide CRISPR interference FACS-based screen to identify modifiers levels neurons. A meta-analysis our publicly available screens identified both specific hits present multiple screens, latter likely responsible for generic protein level maintenance. BORC, complex required anterograde lysosome transport, as modifier protein, mRNA, BORC loss led longer half-life other proteins, suggesting location is proper turnover. As such, function crucial maintaining

Language: Английский

Citations

0
Maintenance of neuronal TDP-43 expression requires axonal lysosome transport DOI Open Access
Veronica H. Ryan,

Sydney Lawton,

Joel F. Reyes

et al.

Published: Jan. 6, 2025

TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate in neurons are not well understood. We generated Halo-TDP-43 knock-in iPSC line performed genome-wide CRISPR interference FACS-based screen to identify modifiers levels neurons. A meta-analysis our publicly available screens identified both specific hits present multiple screens, latter likely responsible for generic protein level maintenance. BORC, complex required anterograde lysosome transport, as modifier protein, mRNA, BORC loss led longer half-life other proteins, suggesting location is proper turnover. As such, function crucial maintaining

Language: Английский

Citations

0
An ANXA11 P93S variant dysregulates TDP‐43 and causes corticobasal syndrome DOI Creative Commons
Allison Snyder, Veronica H. Ryan, James Hawrot

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(8), P. 5220 - 5235

Published: June 26, 2024

Abstract INTRODUCTION Variants of uncertain significance (VUS) surged with affordable genetic testing, posing challenges for determining pathogenicity. We examine the pathogenicity a novel VUS P93S in Annexin A11 (ANXA11) – an amyotrophic lateral sclerosis/frontotemporal dementia‐associated gene corticobasal syndrome kindred. Established ANXA11 mutations cause aggregation, altered lysosomal‐RNA granule co‐trafficking, and transactive response DNA binding protein 43 kDa (TDP‐43) mis‐localization. METHODS described clinical presentation explored phenotypic diversity variants. P93S's effect on function TDP‐43 biology was characterized induced pluripotent stem cell‐derived neurons alongside multiomic neuronal microglial profiling. RESULTS were linked to cases. led decreased lysosome colocalization, neuritic RNA, nuclear cryptic exon expression. Multiomic signatures implicated immune dysregulation interferon signaling pathways. DISCUSSION This study establishes pathogenicity, broadens spectrum mutations, underscores dysfunction pathophysiology, demonstrates potential cellular models determine variant Highlights is pathogenic variant. Corticobasal part spectrum. Hybridization chain reaction fluorescence situ hybridization (HCR FISH) new tool detection exons due TDP‐43‐related loss splicing regulation. Microglial related pathways are important drivers disease. Cellular powerful tools adjudicating variants significance.

Language: Английский

Citations

3
Proteomics applications in next generation induced pluripotent stem cell models DOI

Vyshnavi Manda,

Jay Pavelka,

Edward Lau

et al.

Expert Review of Proteomics, Journal Year: 2024, Volume and Issue: 21(4), P. 217 - 228

Published: March 21, 2024

Introduction Induced pluripotent stem (iPS) cell technology has transformed biomedical research. New opportunities now exist to create new organoids, microtissues, and body-on-a-chip systems for basic biology investigations clinical translations.

Language: Английский

Citations

1