Biology subjects

Lopez, J. A.

Publications and source records attributed to Lopez, J. A..

At least 19 recordsLinked to original sources

bioRxiv2026

Structural and mutational analyses define distinct molecular routes to broad SARS-CoV-2 receptor-binding domain recognition

Broadly reactive antibodies elicited by SARS-CoV-2 infection or vaccination can reveal conserved viral vulnerabilities and inform vaccines with broad coronavirus coverage. Here, we characterize two human-derived monoclonal antibodies, B2014 and C5078, that recognize conserved epitopes on the SARS-CoV-2 RBD and retain activity across antigenically distinct variants. Notably, C5078 also recognizes diverse sarbecoviruses and remains active against currently circulating variants, including XFG and NB.1.8.1. Cryo-EM structures reveal that B2014 recognizes an epitope adjacent to the class 3 antibody site, whereas C5078 targets the highly conserved, cryptic site V epitope. Structural analysis defines how C5078 uses affinity-matured interactions to engage conserved RBD residues, providing a molecular basis for its exceptional breadth. Deep mutational scanning across multiple SARS-CoV-2 variant backgrounds further defines potential pathways of antibody escape, explaining the loss of B2014 activity against antigenically evolved variants while revealing a high barrier to escape from C5078. Together, these findings define distinct structural solutions for broad RBD recognition and highlight conserved, mutationally constrained epitopes that may serve as targets for vaccines designed to elicit antibody responses resilient to ongoing SARS-CoV-2 evolution and future sarbecovirus emergence.

biophysics↗

bioRxiv2026

Lamin A/C regulates the compartment-specific contributions of immune and stromal cells to intestinal inflammation and colitis-associated colon cancer

Inflammatory bowel disease (IBD) arises from dysregulated crosstalk between innate immune, adaptive immune, and stromal compartments, yet the compartment-specific mechanisms driving tissue injury and tumorigenesis remain incompletely defined. To address this gap, we used conditional knockout and overexpression mouse models together with human IBD biopsy analysis to dissect the compartment-specific roles of lamin A/C in intestinal inflammation and colitis-associated tumorigenesis. Pan-hematopoietic lamin A/C deletion attenuated acute dextran sulfate sodium (DSS)-induced colitis. Myeloid-specific lamin A/C deletion ameliorated chronic colitis and was associated with altered dendritic cell (DC) programs, enhanced regulatory T cell (Treg) responses, and reduced effector T cell activation. Adoptive transfer of lamin A/C-deficient bone marrow-derived DCs recapitulated this reduced-damage phenotype in DSS colitis, while proteomic profiling revealed reduced antigen-processing and inflammatory programs together with enhanced metabolic and mucosal defense pathways. T cell-specific lamin A/C deletion reduced the Th1/Treg ratio and limited tumor development by suppressing chronic inflammation, whereas T cell-specific lamin A/C overexpression promoted severe Th1-skewed pathology, sustained intestinal inflammation, and increased colitis-associated tumor burden. Stromal fibroblast-specific lamin A/C deletion generated a tissue-protective niche characterized by enhanced epithelial barrier gene expression, regulatory cytokine production, and remodeling of the local immune milieu. Human IBD biopsies revealed compartment-specific lamin A/C alterations consistent with the murine findings. In lamina propria CD3 T cells, lamin A/C levels were blunted in IBD and associated with local histological severity rather than IBD diagnosis, whereas epithelial lamin A/C showed a steeper crypt-axis spatial gradient in a Crohns disease-specific pattern. Together, these findings identify lamin A/C as a cell-type- and context-dependent regulator of intestinal inflammation and tumorigenesis.

immunology↗

bioRxiv2026

Path-dependent recovery of the gut microbiome after antibiotics emerges from coupled ecological and evolutionary dynamics

Recovery of the gut microbiome after antibiotic exposure is often incomplete and variable, and the processes underlying this variation remain unclear. We performed longitudinal shotgun metagenomic sequencing of 2876 daily fecal samples from replicated humanized and conventional mouse cohorts exposed to controlled antibiotic perturbations. Metagenomic profiling recapitulated ecological trajectories previously observed by 16S sequencing, while revealing extensive strain-level dynamics, including reproducible sweeps of standing variants and de novo mutations in antibiotic target sites and regulatory loci. We also identified genetic changes whose effects depended on community composition, competitive release, and perturbation history. Cross-housing experiments revealed bidirectional strain transfer, with antibiotic-induced niche clearance enabling replacement of resident strains. In parallel, phage dynamics were heterogeneous and clustered by cage. Together, these findings show that post-antibiotic microbiome recovery is a path-dependent process shaped by selection, transmission, and phage activity, producing divergent outcomes even among closely matched communities exposed to the same perturbations.

microbiology↗

bioRxiv2026

Phage-based microbiome manipulation reveals ecological interactions within gut communities

Mechanistic understanding of gut ecology is limited by the availability of tools for precise manipulation of microbiome composition. Here, we isolate lytic phages to enable targeted removal of gut commensal Escherichia fergusonii (Ef) from complex, undefined stool-derived in vitro communities. A single phage drove resistance without fitness cost in monoculture, but resistant Ef exhibited reduced fitness in communities, enabling expansion of closely related Proteobacteria. Resistance arose via reversible promoter inversion linked to outer-membrane function. A phage cocktail overcame resistance to achieve Ef knockout across communities with minimal collateral effects. Using knockout communities, we show that Ef is necessary and sufficient for preventing Salmonella invasion. Replacement with an Ef transposon-mutant library revealed that community-specific fitness defects are enriched in genes involved in outer-membrane assembly. Disruption of these genes sensitized Ef to antagonistic community members, highlighting interspecies warfare as a key driver of microbiome ecology. These results establish phage-mediated perturbation as a framework for linking species to community-level function and for enabling precision microbiome engineering.

microbiology↗

bioRxiv2026

A chromosome-level reference genome for Pacific herring (Clupea pallasii) from the Bering Sea

Pacific herring (Clupea pallasii) serve as a critical trophic link between plankton and many marine species targeted by fisheries. With a broad distribution throughout the North Pacific Ocean, from the Arctic to temperate latitudes, herring hold ecological, economic, and cultural importance. Despite this importance, genomic resources for this species, such as reference genome sequences, have only recently become available. To date, only one scaffold-level reference genome, representing a specimen from the Gulf of Alaska (Vancouver; 1,379 scaffolds), has been published to NCBI. Addressing this data gap, we produced a high quality 795Mb genome sequence organized into 26 chromosomes combining long read sequencing with short read sequencing of proximity ligation libraries. Our assembly is highly complete (BUSCO score of 97.7%) and contiguous (922 contigs, N50 = 7,338,470, L50 = 38; 26 scaffolds, N50 = 31,494,017; L50 = 12). Pacific herring south of the Aleutian Islands and the Alaska Peninsula are genetically differentiated from those in the Bering Sea, making a reference genome from the eastern Bering Sea an important addition to the Pacific herrings genomic toolbox.

genomics↗

bioRxiv2026

Latent cytomegalovirus disrupts NK cell responses to P. falciparum and impairs parasite control

BackgroundNK cells are major innate and adaptive responders to malaria, with multiple roles in protection. Function of NK cells is heterogeneous, underpinned by expression of a diversity of receptors. One driver of NK cell heterogeneity is latent CMV infection, which drives the expansion of memory-like NK cells. We have recently reported that latent CMV infection can negatively impact the adaptive immune response to malaria, but whether CMV-mediated changes to the NK cell compartment also impact innate responses to malaria is unknown. MethodsWe investigated the impact of latent CMV infection on NK cell response to the malaria parasite Plasmodium falciparum in vitro, and in CMV seronegative and seropositive individuals during controlled human malaria infection. We analysed NK cell activation, cytotoxicity and NK cell receptor expression. Additionally, we investigated the impact of CMV serostatus on cytokine production in response to TLR stimulation in the myeloid cell compartment. The impact of CMV and NK cell responses on parasite control and malaria symptoms was investigated. ResultsNK cells from CMV seropositive individuals had reduced responsiveness to P. falciparum parasites in vitro and had reduced activation during controlled human infection. Reduced activation was not restricted to NK subsets modulated by CMV but occurred across the entire NK cell compartment. Consistent with global NK cell attenuation, IL-12 production from myeloid cells, a response that supports NK cell activation on exposure to P. falciparum parasites, was lower in CMV infected individuals. Linking NK cell activation to clinical outcomes, NK cells expressing perforin were associated with parasite control in CMV seronegative individuals. ConclusionCMV infection modulates NK cell responses during malaria by disruption of IL-12, leading to reduced parasite control.

immunology↗

bioRxiv2025

Genetic Ablation and Multi-Omics Profiling Reveal CEP55 as a Key Driver of Tumorigenesis in Diverse Cancer Models

BackgroundCEP55 is a centrosomal protein with emerging oncogenic roles. It is overexpressed in many cancers, where it drives genomic instability, phenocopies PTEN loss and hyperactivates the PI3K/AKT pathway, thereby promoting aggressive and therapy-resistant tumors. MethodsWe developed an inducible Cep55 knockout (KO) mouse model as well as generated primary, immortalized (SV40), and transformed (E1A/Ras) mouse embryonic fibroblasts (MEFs) for functional and proteomic assays. Tumorigenesis was studied using E1A/Ras MEF transplantation and a Pten-deficient genetically engineered mouse model (GEMM). Multi-omics apparatus including proteomics, and spatial transcriptomics, histopathology, immunobloting and functional assays were employed to elucidate underlying mechanisms. Findings were cross-validated using human cancer datasets. ResultsCep55 ablation remodeled the extracellular matrix (ECM), disrupted integrin and oncogenic signaling, reduced AKT/ERK activation, and induced stress pathways. Cep55 knockouts (KO) cells showed impaired proliferation, migration, invasion, and adhesion. In vivo, unlike the embryonic lethality observed in constitutive KOs, the inducible Cep55 deletion was well-tolerated in adult mice. Strikingly, tumors derived from Cep55-null EIA/RAS-transformed MEFs exhibited delayed onset and progression. In the genetically engineered cancer-prone mouse model, Cep55 deletion on a Pten-deficient background led to a greater than seven-fold increase in median survival. Spatial transcriptomics on cancerous tissues revealed that CEP55 regulates ECM remodeling, integrin expression, trafficking, and cell adhesion, supporting its critical role in tumor progression to metastasis. ConclusionCEP55 is dispensable for adult homeostasis but essential for tumorigenesis, especially with PTEN loss. Its deletion suppresses transformation, delays tumor growth, and prolongs survival, supporting CEP55 as a therapeutic target in PTEN-deficient cancers. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/685219v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@3d81e8org.highwire.dtl.DTLVardef@1bd5a7org.highwire.dtl.DTLVardef@167ecf3org.highwire.dtl.DTLVardef@1f57b95_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2025

Gut microbe-derived lactic acid optimizes host energy metabolism during starvation

Gut microbes convert dietary compounds into an array of metabolites that can directly provide energy to their host and indirectly impact host metabolism as systemic endocrine signals. Here, we show that gut microbe-derived metabolites can extend Drosophila melanogaster survival during starvation, despite minimal alteration of dietary energy intake. Combining survival assays with mathematical modeling and untargeted metabolomics, we identify a single, dominant mediator of starvation resilience: lactic acid produced by the commensal bacterium Lactiplantibacillus plantarum. We discover that the basis of starvation resilience is not catabolism of lactic acid using lactate dehydrogenase, but rather increased dietary energy yield through lactic acid-driven promotion of oxidative phosphorylation. Our findings emphasize the role of the microbiome as a source of endocrine cues coordinating host metabolism and underscore the potential of microbiome-derived metabolites as therapeutic molecules for manipulating metabolic health and preventing disease.

physiology↗

bioRxiv2025

When is microbial cross-feeding evolutionarily stable?

Cross-feeding, a phenomenon in which organisms share metabolites, is frequently observed in microbial communities across the natural world. One of the most common forms is waste-product cross-feeding, a unidirectional interaction in which the waste products of one microbe support the growth of another. Despite its ubiquity, it is not well-understood why waste-product cross-feeding persists when a single organism could in principle perform both the producer and consumer role. To address this question, we first analyze cross-feeding evolution in a minimal model of microbial metabolism. The model describes multi-step extraction of energy from a substrate in a simple but thermodynamically correct formulation. Surprisingly, we find that cross-feeding is never evolutionarily stable in this model. By analyzing models with more complex growth functions, we identify a novel mechanism for the evolutionary stability of waste-product cross-feeding, namely, generalized intracellular metabolite toxicity. Such toxicity arises because, in excess, the same intracellular metabolites that cells require for metabolism can be detrimental to growth (e.g., due to osmotic stress). We show that some but not all forms of such toxicity can lead to evolutionarily stable consortia of microbes that cross-feed waste products. This stability results from the potential of such consortia to divide the burden of toxic metabolites among a larger population, allowing them to perform their collective metabolism more efficiently than non-cross-feeders. More generally, we predict that growth penalties that scale nonlinearly with intracellular metabolite levels promote cross-feeding. We find that this mechanism for cross-feeding evolutionary stability implies nontrivial population dynamics, such as a discontinuity in population biomass at the onset of cross-feeding. Significance statementThe chemical reactions performed by microbes have large impacts on our world: from nitrification within the nitrogen cycle to the breakdown of fiber in animal digestive tracts. A striking commonality in many of these processes is that the chemical reactions are a collective effort, with the complete reaction subdivided between many microbes. This phenomenon is known as cross-feeding, and its origins are poorly understood. Understanding the eco-evolutionary forces promoting cross-feeding have the potential to not only enhance our understanding of natural ecosystems, but also improve our ability to engineer such distributed reactions in biotechnology. Here, we develop mathematical theory for the evolution of a common type of cross-feeding and provide predictions for what metabolic and environmental conditions promote this behavior.

microbiology↗

bioRxiv2025

Cryptic diversity arises from glacial cycles in Pacific herring, a critical forage fish

Forage fishes are biological drivers throughout the Pacific Ocean, from the Arctic to nearly subtropical latitudes. As a critical trophic link, the health and stability of Pacific herring (Clupea pallasii) populations have implications for other marine species, including several targeted by large, productive fisheries. Previous research has indicated marked divergence between Pacific herring in the Bering Sea and the Gulf of Alaska. Seeking to localize this biogeographic break, we generated low coverage whole genome resequencing data for 120 Pacific herring from seven sites across the northern Gulf of Alaska and the eastern Bering Sea and Aleutian Islands. Single nucleotide polymorphisms across the mitogenome (267) and nuclear genome ([~]5.6 million) corroborate a biogeographic break in Pacific herring along the Alaska Peninsula and Aleutian Islands, as far west as Unalaska. We identified two distinct populations: one exists along the northern coasts of the Aleutian Islands and in the eastern Bering Sea; the other occupies the southern edge of the Aleutians and the Gulf of Alaska. Two mitochondrial haplogroups co-occurring at collection sites across the Gulf of Alaska suggest secondary contact between two populations, likely representing glacial refugia. Our results underscore the importance of geological events to contextualize the diversification of forage fish species.

genomics↗

bioRxiv2025

Loss of Gαq reshapes key fibroblast traits and drives matrix remodeling and aggressive progression of oral cancer tumors

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive cancer, with limited therapeutic options and a high mortality rate, primarily due to metastasis and recurrence. Tumor-stroma interactions, and namely cancer-associated fibroblasts (CAFs), are pivotal in shaping HNSCC progression. CAFs remodel the extracellular matrix (ECM) and secrete factors and vesicles that promote tumor growth and metastasis. The interplay between autophagy and endosomal/exosomal pathways has been suggested to regulate cellular secretory functions, but their potential involvement in HNSCC progression remains poorly understood. Since we have recently uncovered Gq as a key modulator of autophagy, we have investigated the impact of Gq loss on fibroblast functionality and on its crosstalk with oral HNSCC cells. We report that the absence of Gq rewires murine embryonic fibroblasts towards CAF-like traits, leading to an increased pro-tumorigenic capacity of co-cultured human oral cancer cells through enhanced collagen I deposition and ECM remodeling. Strikingly, fibroblasts lacking Gq display a shift in the balance of intracellular trafficking, degradative and secretory pathways. Exosomes released from Gq-deficient fibroblasts show a marked enrichment in tumor-growth factor receptors and can facilitate aberrant tumor growth of HNSCC cells. Gq-silenced fibroblasts promote the formation of "railroad-tracks" structures around HNSCC cells, enhancing their migratory and invasive capabilities both in vitro and in vivo, and reduced Gq expression in human HNSCC CAFs correlates with enhanced tumor progression. Overall, our data put forward Gq as a key regulator of the HNSCC tumor microenvironment by modulating fibroblast plasticity and functionality.

cancer biology↗

bioRxiv2025

Arabidopsis INHIBITOR OF GROWTH 2 (ING2) promotes flowering by regulating NuA4-dependent histone H4 acetylation levels at FT and SOC1 chromatin loci

INHIBITOR OF GROWTH (ING) proteins are chromatin readers that bind trimethylated histone H3 lysine (K) 4 (H3K4me3) marks and associate with either histone acetyltransferase or deacetylase complexes to activate or repress gene transcription, respectively. In plants, there are two types of ING proteins named ING1 and ING2. Here we report that Arabidopsis ING2 associates with multiple subunits of the histone H4 acetyltransferase complex NuA4, controls genome-wide levels of histone H4 acetylation (H4ac) and regulates different developmental processes including the initiation of flowering. Our data indicates that ING2 biological functions are largely independent of ING1 activity. We find that ING2 is recruited to the chromatin of key floral integrators such as FT and SOC1, and is required for their timely activation by modulating histone H4ac levels at these loci. Besides, our observations reveal a genetic interaction between ING2 and genes encoding relevant proteins for H3K4me3 or H2A.Z deposition, suggesting that ING2 might represent a hub for potential crosstalk between histone H4ac and these histone modifications/variants.

plant biology↗

bioRxiv2025

Integrative multi-layer workflow for quantitative analysis of post-translational modifications

Novel algorithms based on ultratolerant database searching have paved the way for comprehensive analysis of all possible post-translational modifications (PTM) that can be detected by mass spectrometry-based proteomics, obviating their prior knowledge. These tools together with novel quantitative statistical models allow hypothesis-free approaches to study the role and impact of PTM on biological systems. However, interpretation of this information from a pathophysiological perspective is challenging due to the huge amounts of PTM data, the existence of chemical, structural, and statistical artifacts and the lack of dedicated tools for their analysis. Here we propose a novel integrative workflow that automatically captures several layers of PTM-related information, including variations in trypsin efficiency, zonal changes, specific PTM changes and hypermodified regions, allowing advanced control of artefacts and coherent and comprehensive interpretation of PTM data. We show the performance of the new workflow by reanalyzing proteomics data from animal models of mitochondrial heteroplasmy and ischemia/reperfusion, revealing relevant PTM information not previously detectable, including consistent detection of novel oxidative modifications in Met and Cys residues from raw proteomics data. The workflow is available through the application PTM-compass.

bioinformatics↗

bioRxiv2025

Modeling the acutely injured brain environment in vitro.

A major challenge to study the regenerative potential of the injured brain is the limited access to this organ in vivo. To address this, we developed an innovative gliosis model that, although established in vitro, originates from a genuine injury in vivo. The model relies on reactive glia acquiring enhanced adhesion, facilitating their rapid adaptation to in vitro conditions, where it faithfully recapitulates key features of brain injury. These include a secretome associated with injury pathways, degenerative responses like neuronal death and neuroinflammation, and regenerative processes such as progenitor proliferation, recruitment and commitment to oligodendrocytes. Moreover, the exposure of adult glial cells to this culture medium recapitulates their acquisition of multipotency observed in both mouse and human injured brains. Finally, our approach allows studying glia-to-neuron reprogramming, a process challenging to tackle in vivo. Consequently, we present a novel tool for exploring stem cell dynamics and regenerative behaviors in CNS pathology.

neuroscience↗

bioRxiv2024

Age is an intrinsic driver of inflammatory responses to malaria

Age is a critical factor influencing the host immune response to infection and disease pathogenesis. In malaria, the risk of severe disease increases with age in non-immune individuals. Malaria severity is in part driven by inflammation, but the specific cells and mechanisms contributing to age-dependent disease risk are incompletely understood. Here, we assessed inflammatory cytokines in non-immune children and adults with clinical malaria, and the phenotypic, functional and transcriptional differences of in vitro innate cell responders to malaria parasites in naive children and adults. During naturally acquired malaria, age was associated with increased plasma levels of inflammatory chemokines CCL2, CCL3, CXCL8, CXLC9, along with CRP, and IDO, which were associated with clinical symptoms. In malaria naive individuals, classical monocyte and V{delta}2+ {gamma}{delta} T cell responses from adults were characterized by higher inflammatory cytokine production, and transcriptional activation following stimulation with malaria parasites. Classical monocyte responses in adults were dominated by CCL2 production, while in children the response had increased IL10 production and enrichment in IL10 signaling pathways upon parasite stimulation. This heightened inflammatory response in adults was not mitigated by parasite induced Tregs. Taken together, these findings identify cellular mechanisms of age-dependent host responses that play crucial roles in driving inflammatory responses in malaria.

immunology↗

bioRxiv2024

Latent cytomegalovirus is associated with reduced functional antibody induction following Plasmodium falciparum infection

Human immune responses to infection and vaccination are heterogenous, driven by multiple factors including genetics, environmental exposures and personal infection histories. For malaria caused by Plasmodium falciparum parasites, host factors that impact on humoral immunity are poorly understood. We investigated the role of latent cytomegalovirus (CMV) on the host immune response to malaria using blood stage P. falciparum Controlled Human Malaria Infection (CHMI) and in a MSP1 vaccine Phase 1a clinical trial. CMV seropositivity was associated with reduced induction of parasite specific antibodies following malaria infection and vaccination. During infection, reduced antibody induction was associated with modifications to the T -follicular helper (Tfh) cell compartment. CMV seropositivity was associated with a skew towards Tfh1 cell subsets before and after malaria infection, and reduced activation of Tfh2 cells. Protective Tfh2 cell activation was only associated with antibody development in CMV seronegative individuals, and a higher proportion of Tfh1 cells was associated with lower antibody development in CMV seropositive individuals. During MSP1 vaccination, reduced antibody induction in CMV seropositive individuals was associated with CD4 T cell expression of terminal differentiation marker CD57. These findings are particularly relevant for malaria endemic regions where CMV infection is acquired early in life and may modify immunity to malaria gained during infection or vaccination.

immunology↗

bioRxiv2024

Unfolded Von Willebrand Factor Binds Protein S and Reduces Anticoagulant Activity

Protein S (PS), the critical plasma cofactor for the anticoagulants tissue factor (TF) pathway inhibitor (TFPI) and activated protein C (APC), circulates in two functionally distinct pools: free (anticoagulant) or bound to complement component 4b-binding protein (C4BP) (anti-inflammatory). Acquired free PS deficiency is detected in several viral infections, but its cause is unclear. Here, we identified a shear-dependent interaction between PS and von Willebrand Factor (VWF) by mass spectrometry. Consistently, plasma PS and VWF comigrated in both native and agarose gel electrophoresis. The PS/VWF interaction was blocked by TFPI but not APC, suggesting an interaction with the C-terminal sex hormone binding globulin (SHBG) region of PS. Microfluidic systems, mimicking arterial laminar flow or disrupted turbulent flow, demonstrated that PS stably binds VWF as VWF unfolds under turbulent flow. PS/VWF complexes also localized to platelet thrombi under laminar arterial flow. In thrombin generation-based assays, shearing plasma decreased PS activity, an effect not seen in the absence of VWF. Finally, free PS deficiency in COVID-19 patients, measured using an antibody that binds near the C4BP binding site in SHBG, correlated with changes in VWF, but not C4BP, and with thrombin generation. Our data suggest that PS binds to a shear-exposed site on VWF, thus sequestering free PS and decreasing its anticoagulant activity, which would account for the increased thrombin generation potential. As many viral infections present with free PS deficiency, elevated circulating VWF, and increased vascular shear, we propose that the PS/VWF interaction reported here is a likely contributor to virus-associated thrombotic risk. Key PointsO_LIVon Willebrand Factor (VWF) binds Protein S (PS) in a shear-dependent manner, reducing the free PS pool and its anticoagulant activity. C_LIO_LIThe PS/VWF complex forms under turbulent flow conditions, is stable in whole blood, and localizes to growing platelet thrombi. C_LI

biochemistry↗

bioRxiv2023

iSanXoT: a Standalone Application for the Integrative Analysis of Mass Spectrometry-Based Quantitative Proteomics Data

Numerous bioinformatics tools currently exist to perform quantitative analysis of proteomics experiments. The majority of these tools apply diverse statistical models to assign a quantitative protein value from the mass-spectrometry information. Here we present iSanXoT, a standalone application that allows integrative analysis of quantitative proteomics data. iSanXoT processes relative abundances between MS signals and integrates them sequentially to upper levels using our previously published Generic Integration Algorithm (GIA). iSanXoT offers unique capabilities that complement conventional quantitative softwares, including statistical weighting and independent modeling of error distributions in each integration, aggregation of technical or biological replicates, quantification of posttranslational modifications or analysis of coordinated protein behavior. iSanXoT is a standalone, user-friendly application which accepts output from widespread proteomics pipelines and enables free construction of quantification workflows and fully customizable reports than can be reused across different projects or shared among users. Diverse integrative workflows constructed using GIA for the analysis of high-throughput quantitative proteomics experiments have been successfully applied in numerous publications. iSanXoT has been tested with the main operating systems. Download links for the corresponding distributions are available at https://github.com/CNIC-Proteomics/iSanXoT/releases.

bioinformatics↗