ANXA2

What is ANXA2 and what are its primary cellular functions?

ANXA2 is a member of the annexin family characterized by calcium-dependent, anionic phospholipid-binding properties. This versatile protein is broadly expressed and distinguished from other annexins by its variable amino-terminal region (approximately 30 amino acids), known as the head region .

ANXA2 exhibits remarkable cellular versatility, functioning in:

• Membrane organization and dynamics during endocytosis and exocytosis

• Gene regulation processes

• Ion channel formation

• Fibrinolysis activities

• Cellular transformation events

The protein can be found in multiple cellular compartments including the nucleus, cytoplasm, membrane, and extracellular space, with its subcellular localization, post-translational modifications, and binding partners dictating its diverse functions . Its discovery traces back to its identification as a substrate of the pp60v-src oncoprotein in transformed chicken embryonic fibroblasts .

What is the difference between monomeric and tetrameric forms of ANXA2?

ANXA2 exists in two primary forms with distinct functions:

• Monomeric ANXA2 (ANXA2m):

  • Functions as a TLR2 ligand and has immunological activity

  • Induces differentiation of antigen-presenting cells (APCs)

  • Promotes expression of CD80 and CD86

  • Stimulates secretion of IL-12, IFN-γ, and TNF-α

  • Enhances cross-priming of murine and human antigen-specific CD8+ T cells

• Tetrameric ANXA2 (ANXA2t):

  • Signals through different pathways than the monomeric form

  • Does not appear to bind TLR2 or stimulate the same immune response as ANXA2m

Significantly, the N-terminal region of ANXA2m is crucial for its immune functions. Research has shown that the amino-terminal 15 amino acids of ANXA2m are both necessary and sufficient for TLR2 binding and dendritic cell activation .

How is ANXA2 expression regulated by oxygen levels?

ANXA2 expression demonstrates oxygen sensitivity, with significant implications for tumor biology. Experimental evidence reveals that:

• ANXA2m is overexpressed by murine glioblastoma GL261 cells cultured under 5% O₂ conditions but not under atmospheric 20% O₂ levels .

• This oxygen-dependent expression pattern suggests ANXA2m may function as a danger-associated molecular pattern (DAMP) that is upregulated under physiologically relevant oxygen concentrations that mirror in vivo tumor environments .

• The oxygen-regulated expression of ANXA2 contributes to the increased efficacy of tumor vaccines derived from GL261 cells grown under 5% O₂ conditions .

Methodologically, researchers confirmed this oxygen regulation through:

• Immunoblot analysis demonstrating increased ANXA2 expression in GL261 cells grown under 5% O₂ compared to 20% O₂

• Co-immunoprecipitation studies verifying binding between ANXA2 and TLR2

• HEK-Blue reporter cell assays confirming that human ANXA2m induces TLR2 signaling

This oxygen-dependent regulation has significant implications for understanding ANXA2's role in the tumor microenvironment and developing ANXA2-based cancer immunotherapies.

What methodologies are most effective for studying ANXA2-protein interactions?

Studying ANXA2-protein interactions requires sophisticated methodological approaches. Based on current research, the following techniques have proven particularly effective:

• X-ray Crystallography:

  • Enables determination of the three-dimensional structure of ANXA2 complexes

  • Allows identification of specific binding interfaces and interaction mechanisms

  • Can be performed at different resolutions (e.g., 1.9 Å and 2.4 Å as reported for different ANXA2 complexes)

• Molecular Replacement for Phase Determination:

  • Utilized with programs like Phaser-MR module of Phenix

  • Previously solved structures (e.g., PDB ID: 5LPU, chain A for human AnxA2) can serve as search models

• Anomalous Diffraction Techniques:

  • Particularly useful for identifying specific atoms in complex structures

  • Data collection at specialized beamlines (e.g., I23 at Diamond Light Source) using specific wavelengths (λ = 2.7552 Å) optimized for anomalous signal detection

  • Enables precise determination of stereochemical configurations (e.g., Rp or Sp phosphorothioate configurations)

• Co-immunoprecipitation:

  • Effective for identifying protein binding partners of ANXA2

  • Has been successfully used to establish ANXA2-TLR2 binding

• Reporter Cell Assays:

  • Systems such as HEK-Blue reporter cells expressing TLR2

  • Allow functional validation of binding by measuring activation of signaling pathways

• Mass Spectrometry:

  • Critical for identifying ANXA2 in complex protein mixtures

  • Has been used to identify ANXA2 as a TLR2-binding protein in immunoprecipitation studies

These methodologies can be combined for comprehensive characterization of ANXA2 interactions, as demonstrated in studies examining both structural details and functional consequences of these interactions.

How does ANXA2 function in immune regulation through TLR2 signaling?

ANXA2, specifically in its monomeric form (ANXA2m), functions as a novel immune regulator through TLR2 signaling with multiple downstream effects:

• Dendritic Cell Maturation:

  • ANXA2m induces both murine and human dendritic cell maturation through TLR2

  • Upregulates costimulatory molecules CD80 and CD86 on dendritic cells, essential for T cell activation

• Cytokine Production:

  • Stimulates secretion of pro-inflammatory and immunostimulatory cytokines:

    • IL-12p70: Critical for Th1 differentiation and cellular immunity

    • TNF-α: Promotes inflammation and anti-tumor responses

    • IFN-γ: Key for anti-viral and anti-tumor immune mechanisms

• Antigen Cross-Presentation:

  • Enhances the ability of dendritic cells to cross-present antigens to CD8+ T cells

  • This process is fundamental for generating cytotoxic T cell responses against tumors

• Structural Determinants:

  • The amino-terminal 15 amino acids of ANXA2m are both necessary and sufficient for:

    • TLR2 binding

    • Dendritic cell activation

    • Immune stimulation

• Adjuvant Activity:

  • When combined with antigens like chicken ovalbumin (OVA), ANXA2m functions as an adjuvant

  • Enhances antigen-specific CD8+ T cell responses in vaccinated mice

Methodologically, these functions have been established through:

• In vitro studies with TLR2-expressing reporter cells

• Experiments with immature dendritic cells

• Vaccination studies comparing TLR2-/- and TLR2+/+ mice

• Analyses of cytokine secretion profiles and T cell responses

This TLR2-mediated immune activity positions ANXA2m as a potential danger-associated molecular pattern (DAMP) that can be exploited for cancer immunotherapy, particularly in developing vaccines against tumors like glioblastoma.

How can ANXA2 be exploited for cancer vaccine development?

ANXA2's unique properties make it a promising candidate for cancer vaccine development, particularly through several strategic approaches:

• ANXA2-Antigen Fusion Peptides:

  • The amino-terminal 15 amino acids of ANXA2m are sufficient for TLR2 stimulation

  • These can be fused with tumor antigens to create compact immunogenic molecules

  • Fusion peptides could be as short as 30 amino acids if one or two CD8+ T cell epitopes are joined to the ANXA2 amino terminal portion

• Personalized Cancer Vaccines:

  • "Off-the-shelf" agents containing common tumor antigens fused to ANXA2 peptides

  • "Personalized" vaccines synthesized after tumor sequencing to identify tumor-specific neo-antigens

• Combination Strategies:

  • ANXA2 peptide fusions could be combined with established TLR agonists

  • Such combinations may induce synergistic effects in preclinical cancer models

• Oxygen-Regulated Vaccine Production:

  • Utilizing the increased expression of ANXA2 under 5% O₂ conditions

  • Cell lines grown under physiologically relevant oxygen levels could enhance the adjuvant activity of tumor cell-derived vaccines

• Methodological Considerations:

  • Fusion peptide design should focus on the N-terminal region of ANXA2

  • Validation requires both in vitro testing with dendritic cells and in vivo vaccination studies

  • Assessment of CD8+ T cell responses is crucial for efficacy determination

These approaches exploit ANXA2's dual role as both an immune stimulator through TLR2 and as a tumor-associated molecule that is often overexpressed in cancer contexts. Further research in glioma models will determine the efficacy of ANXA2-based vaccine strategies, potentially providing new immunotherapeutic options for difficult-to-treat cancers.

How can ANXA2 serve as a biomarker for cancer prognosis and immune infiltration?

ANXA2 has emerged as a potential biomarker for cancer prognosis and immune infiltration, with significant implications for patient stratification and treatment selection:

• Correlation with Immune Infiltration:

  • ANXA2 expression levels correlate with the infiltration of 24 types of immune cells in tumors

  • These correlations have been established using Spearman's rank correlation coefficient analyses

• Association with Immune Checkpoints:

  • ANXA2 expression correlates with the expression of 47 immune checkpoint molecules

  • This suggests ANXA2 may influence the immunosuppressive tumor microenvironment

• Relationship with Tumor Microenvironment Scores:

  • ANXA2 expression has been correlated with:

    • StromalScore: Indicates the presence of stromal cells in tumor tissue

    • ImmuneScore: Reflects immune cell infiltration

    • ESTIMATEScore: Combines both stromal and immune components

• Connection to Genomic Instability Markers:

  • ANXA2 expression has been associated with:

    • Tumor Mutation Burden (TMB)

    • Microsatellite Instability (MSI)

    • Mismatch Repair (MMR) status

• Methodological Approaches for Analysis:

  • Differential expression analysis using Wilcoxon rank sum test and Wilcoxon signed rank test

  • Survival analysis via log-rank test to correlate ANXA2 expression with patient outcomes

  • Correlation with tumor TNM staging using Kruskal-Wallis test

  • Assessment of correlation with immune parameters using Spearman's rank correlation coefficient

• Pathway Analysis:

  • Gene Set Enrichment Analysis (GSEA) has been employed to identify ANXA2-related signaling pathways

  • Significant pathways are determined using adjusted p-value (<.05), normalized enrichment score (|NES| > 1), and False Discovery Rate (FDR, q value < .25)

These findings collectively suggest that ANXA2 widely correlates with immune infiltration and may function as a promising prognostic biomarker across various tumor types. The integration of ANXA2 expression data with immune and genomic parameters could enhance patient stratification for immunotherapy and other treatment modalities.

What structural insights have been gained about ANXA2 through crystallography studies?

Crystallographic studies have provided crucial insights into ANXA2's structure and interactions, particularly with nucleic acids:

These structural insights provide a molecular foundation for understanding how ANXA2 interacts with modified nucleic acids, which has implications for its biological functions and potential therapeutic applications.

What are the optimal methods for analyzing ANXA2 expression in tissue samples?

Analyzing ANXA2 expression in tissue samples requires a multi-faceted approach that combines molecular, cellular, and computational techniques:

• Immunohistochemistry (IHC):

  • Allows visualization of ANXA2 expression and localization in tissue sections

  • Can distinguish between membrane, cytoplasmic, and nuclear localization

  • Enables correlation of expression with histopathological features

  • Quantification can be performed using digital image analysis systems

• Western Blotting:

  • Provides semi-quantitative assessment of ANXA2 protein levels

  • Can differentiate between monomeric and tetrameric forms of ANXA2

  • Has been successfully used to demonstrate oxygen-dependent expression differences

• Quantitative Real-Time PCR (qRT-PCR):

  • Measures ANXA2 mRNA expression levels

  • Allows normalization to housekeeping genes for accurate comparisons

  • Can detect subtle differences in expression across different conditions

• RNA Sequencing (RNA-Seq):

  • Provides comprehensive transcriptomic data including ANXA2 expression

  • Enables correlation with other genes and pathway analysis

  • Used in Gene Set Enrichment Analysis (GSEA) to identify ANXA2-related signaling pathways

• Tissue Microarrays (TMAs):

  • Allow high-throughput analysis of ANXA2 expression across multiple patient samples

  • Facilitate correlation with clinical parameters and outcomes

• Statistical Analysis Methods:

  • Wilcoxon rank sum test and Wilcoxon signed rank test for differential expression analysis

  • Kruskal-Wallis test for correlation with tumor staging

  • Spearman's rank correlation coefficient for evaluating associations with immune infiltration and other parameters

• Computational Approaches:

  • Use of established R packages like "clusterProfiler" for pathway analysis

  • Application of criteria such as adjusted p-value (<.05), normalized enrichment score (|NES| > 1), and False Discovery Rate (FDR, q value < .25) for determining statistical significance

When implementing these methods, researchers should consider tissue-specific optimization, appropriate controls, and correlation with clinical data to maximize the translational value of the findings.

How can researchers effectively study ANXA2's role in cancer cell migration and invasion?

Studying ANXA2's role in cancer cell migration and invasion requires sophisticated experimental approaches that span from molecular manipulation to advanced imaging techniques:

• Gene Manipulation Techniques:

  • CRISPR-Cas9 gene editing for creating ANXA2 knockout cell lines

  • RNA interference (siRNA/shRNA) for transient or stable ANXA2 knockdown

  • Overexpression systems using plasmid vectors with wild-type or mutant ANXA2

  • Site-directed mutagenesis to target specific functional domains of ANXA2

• In Vitro Migration Assays:

  • Wound healing (scratch) assays to assess collective cell migration

  • Transwell migration assays to evaluate chemotactic responses

  • Boyden chamber assays with Matrigel coating to assess invasive capacity

  • Single-cell tracking experiments with time-lapse microscopy for detailed migration dynamics

• 3D Culture Models:

  • Spheroid invasion assays in collagen or Matrigel matrices

  • Organoid cultures to better recapitulate in vivo tissue architecture

  • Microfluidic devices to create defined gradients and monitor directional invasion

• Live Cell Imaging Techniques:

  • Fluorescently-tagged ANXA2 (e.g., GFP-ANXA2 fusion proteins) for tracking localization during migration

  • FRET-based sensors to monitor ANXA2 interactions with binding partners

  • Super-resolution microscopy to visualize subcellular distribution during migration events

• Protein-Protein Interaction Analyses:

  • Co-immunoprecipitation to identify migration-related binding partners

  • Proximity ligation assays to visualize interactions in situ

  • Mass spectrometry to identify post-translational modifications affecting migration

• In Vivo Models:

  • Orthotopic xenograft models with ANXA2-modified cancer cells

  • Intravital microscopy to track cancer cell migration in living animals

  • Circulating tumor cell (CTC) analysis to assess ANXA2's role in metastatic potential

• Molecular Pathway Analysis:

  • Phosphoproteomic analysis to identify signaling pathways affected by ANXA2

  • Western blotting for key mediators of cell migration (e.g., focal adhesion kinase, Rho GTPases)

  • Transcriptomic analysis to identify genes regulated by ANXA2 that influence migration

• Extracellular Matrix (ECM) Interaction Studies:

  • Atomic force microscopy to measure cell-ECM adhesion forces

  • Traction force microscopy to quantify forces generated during migration

  • Zymography to assess matrix metalloproteinase activity influenced by ANXA2

These methodologies can be used in combination to comprehensively characterize how ANXA2 contributes to the migratory and invasive phenotype of cancer cells, potentially revealing new therapeutic targets or prognostic indicators.

What strategies can target ANXA2 for cancer immunotherapy?

Targeting ANXA2 for cancer immunotherapy represents a promising frontier with several strategic approaches:

• ANXA2-Based Vaccine Development:

  • Creation of fusion peptides combining the TLR2-activating N-terminal region of ANXA2 with tumor antigens

  • Development of peptides as short as 30 amino acids containing the essential 15 amino acids of ANXA2 and tumor-specific epitopes

  • These constructs can function as both antigen carriers and immune adjuvants

• Personalization Approaches:

  • "Off-the-shelf" vaccines containing ANXA2 peptides fused to common tumor antigens

  • Personalized vaccines created after tumor sequencing to identify patient-specific neoantigens

  • Both approaches leverage ANXA2's adjuvant properties while targeting relevant tumor epitopes

• Combination Immunotherapy Strategies:

  • ANXA2-based vaccines combined with established TLR agonists to induce synergistic effects

  • Integration with checkpoint inhibitor therapies to overcome immunosuppression

  • Combination with conventional treatments like radiation to enhance immunogenic cell death

• Ex Vivo Dendritic Cell Manipulation:

  • Loading dendritic cells with ANXA2-antigen constructs to enhance their maturation

  • Utilizing ANXA2's ability to induce DC maturation through upregulation of CD80/CD86

  • Exploiting enhanced antigen cross-presentation capabilities induced by ANXA2

• TLR2-Targeted Approaches:

  • Development of synthetic ANXA2-derived peptides optimized for TLR2 binding

  • Creation of nanoparticles incorporating ANXA2 peptides for enhanced delivery to tumor sites

  • Design of bispecific constructs targeting both TLR2 (via ANXA2) and tumor-specific antigens

• Oxygen-Regulated Expression Exploitation:

  • Utilizing the hypoxia-dependent upregulation of ANXA2 in tumors

  • Targeting therapies to hypoxic tumor regions where ANXA2 expression is enhanced

  • Designing oxygen-sensitive drug delivery systems coupled with ANXA2-targeting agents

• ANXA2-Targeting Antibodies:

  • Development of antibodies that specifically block ANXA2's pro-tumorigenic functions

  • Creation of antibody-drug conjugates targeting ANXA2-expressing tumor cells

  • Engineering of bispecific antibodies linking ANXA2-expressing cells to immune effectors

These strategies collectively offer multiple avenues for harnessing ANXA2's unique properties for cancer immunotherapy, with the potential to address challenges in current immunotherapeutic approaches, particularly for difficult-to-treat cancers like glioblastoma.

How can the oxygen-regulated expression of ANXA2 be exploited in cancer therapy?

The oxygen-regulated expression of ANXA2 presents unique opportunities for targeted cancer therapies:

• Hypoxia-Targeted Therapeutic Approaches:

  • Development of therapies specifically targeting ANXA2 in hypoxic tumor regions

  • Design of prodrugs activated in low-oxygen environments where ANXA2 is overexpressed

  • Creation of oxygen-sensitive nanoparticles for targeted drug delivery to ANXA2-rich hypoxic zones

• Vaccine Production Under Physiological Oxygen Conditions:

  • Generation of tumor cell lysates under 5% O₂ conditions to enhance ANXA2 content

  • This approach has demonstrated increased adjuvant activity compared to cells grown under atmospheric 20% O₂ conditions

  • These oxygen-conditioned vaccines show enhanced efficacy in preclinical models

• Hypoxia-ANXA2-TLR2 Axis Targeting:

  • Exploitation of the hypoxia-induced ANXA2-TLR2 signaling pathway

  • Development of immunotherapeutics that specifically activate or inhibit this pathway

  • Creation of synthetic ANXA2 mimetics optimized for hypoxic tumor environments

• Biomarker Applications:

  • Utilization of ANXA2 expression as a biomarker for tumor hypoxia

  • Stratification of patients based on ANXA2 expression for hypoxia-targeted therapies

  • Monitoring ANXA2 levels as an indicator of treatment response

• Combination Strategies with Hypoxia-Modifying Agents:

  • Coupling ANXA2-targeted therapies with drugs that modify tumor oxygenation

  • Sequential treatment approaches that first normalize tumor vasculature then target ANXA2

  • Combination with hyperbaric oxygen therapy to modulate ANXA2 expression patterns

• Methodological Considerations for Research and Development:

  • In vitro studies should be conducted under physiologically relevant oxygen concentrations (5% O₂)

  • Animal models should include assessment of intratumoral oxygen gradients and corresponding ANXA2 expression

  • Clinical translation requires development of methods to assess tumor hypoxia and ANXA2 expression in patients

• Targeting ANXA2 as a Danger-Associated Molecular Pattern (DAMP):

  • Exploiting ANXA2's role as a hypoxia-induced DAMP to stimulate anti-tumor immunity

  • Development of therapies that enhance the immunostimulatory properties of ANXA2

  • Creation of synthetic DAMP molecules based on ANXA2's structure and function

This oxygen-dependent regulation of ANXA2 offers a unique therapeutic window, potentially allowing for more selective targeting of tumor cells while sparing normal tissues where ANXA2 expression may be lower due to normoxic conditions.

What are the most promising unexplored areas of ANXA2 research?

Several unexplored or underdeveloped areas of ANXA2 research offer significant potential for breakthrough discoveries:

• Single-Cell Analysis of ANXA2 Expression and Function:

  • Application of single-cell RNA sequencing to map ANXA2 expression across diverse cell types within tumors

  • Investigation of cell-specific functions of ANXA2 in complex tissues

  • Exploration of how ANXA2 contributes to cellular heterogeneity in tumors

• ANXA2 in Liquid Biopsy Development:

  • Exploration of ANXA2 as a circulating biomarker in blood or other bodily fluids

  • Development of sensitive detection methods for ANXA2 in liquid biopsies

  • Correlation of circulating ANXA2 levels with tumor burden, response to therapy, and disease progression

• Post-Translational Modifications (PTMs) of ANXA2:

  • Comprehensive mapping of PTMs across different cellular contexts

  • Investigation of how phosphorylation, acetylation, and other modifications affect ANXA2 function

  • Development of PTM-specific antibodies and detection methods

• ANXA2 in the Tumor Microenvironment Beyond Immune Cells:

  • Exploration of ANXA2's role in stromal cells, including cancer-associated fibroblasts

  • Investigation of how ANXA2 mediates tumor-stromal interactions

  • Study of ANXA2's contribution to the extracellular matrix remodeling

• ANXA2 in Non-Canonical Immune Responses:

  • Investigation of ANXA2's role in trained immunity and innate immune memory

  • Exploration of ANXA2's interactions with unconventional T cells and innate lymphoid cells

  • Study of ANXA2's role in immune response to non-canonical stimuli

• Therapeutic Resistance Mechanisms Involving ANXA2:

  • Exploration of how ANXA2 contributes to resistance to various cancer therapies

  • Investigation of ANXA2-targeted approaches to overcome therapy resistance

  • Development of combination strategies targeting ANXA2-related resistance pathways

• ANXA2 in Metabolism and Cancer:

  • Investigation of ANXA2's role in tumor metabolism

  • Exploration of metabolic dependencies in ANXA2-high versus ANXA2-low tumors

  • Study of how metabolic targeting might synergize with ANXA2-directed therapies

• Structural Biology of Full-Length ANXA2 in Various Complexes:

  • Determination of the complete structure of full-length ANXA2, including the flexible N-terminal domain

  • Investigation of ANXA2 in complex with various binding partners

  • Application of cryo-EM to study larger ANXA2-containing complexes

• ANXA2 in RNA Binding and Regulation:

  • Comprehensive mapping of ANXA2-RNA interactions

  • Investigation of ANXA2's role in RNA metabolism and post-transcriptional regulation

  • Exploration of ANXA2 as an RNA-binding protein in stress responses

These unexplored areas represent fertile ground for future research with potential implications spanning from basic molecular understanding to clinical applications in diagnosis, prognosis, and therapy.

What computational approaches can advance ANXA2 research?

Advanced computational approaches can significantly accelerate ANXA2 research across multiple domains:

• Machine Learning for Biomarker Development:

  • Development of AI algorithms to identify patterns in ANXA2 expression across cancer types

  • Creation of predictive models for patient outcomes based on ANXA2 and related biomarkers

  • Design of computational pipelines for integrating ANXA2 data with other clinical and molecular features

• Molecular Dynamics Simulations:

  • Simulation of ANXA2 structural dynamics in various environments

  • Investigation of how phosphorothioate modifications affect ANXA2-nucleic acid interactions

  • Exploration of conformational changes in ANXA2 upon binding to different partners

• Advanced Network Analysis:

  • Construction of protein-protein interaction networks centered on ANXA2

  • Identification of critical nodes and potential therapeutic targets within ANXA2-related pathways

  • Integration of transcriptomic, proteomic, and clinical data into comprehensive network models

• Pathway Enrichment Analysis:

  • Application of Gene Set Enrichment Analysis (GSEA) to identify ANXA2-related pathways

  • Utilization of packages like "clusterProfiler" for comprehensive pathway mapping

  • Implementation of statistical criteria including adjusted p-value (<.05), normalized enrichment score (|NES| > 1), and False Discovery Rate (FDR, q value < .25)

• Structure-Based Drug Design:

  • Virtual screening of compound libraries for molecules targeting specific ANXA2 domains

  • Design of peptidomimetics based on the N-terminal region of ANXA2

  • Development of in silico approaches to optimize ANXA2-targeted therapeutics

• Single-Cell Data Analysis:

  • Development of computational methods for analyzing ANXA2 expression at single-cell resolution

  • Creation of algorithms for spatial transcriptomics data to map ANXA2 expression within tissue contexts

  • Integration of single-cell and spatial data to understand ANXA2's role in tissue architecture

• Multi-Omics Data Integration:

  • Development of methods to integrate genomic, transcriptomic, proteomic, and epigenomic data related to ANXA2

  • Creation of comprehensive databases of ANXA2 function across biological systems

  • Application of tensor factorization and other advanced mathematical approaches for data integration

• Immunoinformatics:

  • Prediction of ANXA2-derived epitopes for vaccine development

  • Modeling of interactions between ANXA2-based constructs and immune receptors like TLR2

  • Design of optimal ANXA2-antigen fusion peptides for cancer immunotherapy

These computational approaches can generate hypotheses for experimental validation, optimize experimental design, and accelerate the translation of ANXA2 research into clinical applications by identifying the most promising directions for further investigation.