Biology subjects

Chowdhury, S.

Publications and source records attributed to Chowdhury, S..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

A Comprehensive Methodological Framework for Anthropometric Head Shape Modeling Using Small Dataset

Detailed anthropometric characterization of complex shapes of human heads can ensure optimal fit, comfort, and effectiveness of head-mounted devices. However, there is a lack of a reliable and systematic approach for head shape classification and modeling for laboratory-based, small, occupation-specific datasets. Therefore, in this study, we proposed a streamlined framework comprising six steps--pre-processing, feature extraction, feature selection, clustering, shape modeling, and validation--for head shape classification and modeling. We collected 36 firefighter 3D head scans and implemented the framework. Different clustering techniques, such as k-means and k-medoids, were evaluated using the squared Euclidean distance of individual head shapes from their cluster centroid. Furthermore, five variations of NURBS and cubic spline methods were assessed to design the representative head shape of each cluster, and their accuracy was evaluated using mean square error (MSE) values. The clustering results indicated that k-means provide better metrics than k-medoids. Among the shape modeling methods, cubic spline least squares displayed the lowest MSE (0.70 cm2)and computational time (0.14 s), whereas NURBS least squares displayed the highest MSE (7.19 cm2). Overall, the framework with k-means clustering and cubic spline least squares modeling techniques proved to be the most efficient for small datasets.

bioengineering↗

bioRxiv2024

Impedance-based assay for pan-cancer early and rapid detection of cell-free DNA

Aberrant DNA methylation is a hallmark of cancer, and plasma cell-free DNA (cfDNA) containing these abnormal methylation patterns has emerged as a promising non-invasive biomarker for pan-cancer detection. However, intrinsic challenges remain that continue to limit its broad clinical application. Here we show a simple and rapid impedance biosensor called Asima Rev that can detect cancer cfDNA in under 5 min without the need for any molecular labelling, electrode modification, signal amplification, or target enrichment steps. Using 216 clinical samples (50 healthy) from 15 different cancer types (all stages) we show an overall sensitivity and specificity of 96.4% and 94.0%, respectively. Differences in methylation content between cancerous and healthy cfDNA lead to distinct solvation behaviour and electro-physicochemical property that remain consistent across cancer types regardless of the distribution patterns of methyl cytosine. Our test exploits this inherent difference.

biophysics↗

bioRxiv2024

The climatic determinants of flexible reproductive seasonality in Africa-dwelling papionins

At a time when seasonal cycles are increasingly disrupted, the ecology and evolution of reproductive seasonality in tropical vertebrates remains poorly understood. In order to predict how changes in seasonality might affect these animals, it is important to understand which aspects of their diverse patterns of reproductive phenology are linked to either the equally diverse patterns of rainfall seasonality (within-year variations) or instead the marked climatic unpredictability (year-to-year variations) occurring across the intertropical belt. Here, we gather birth and climatic seasonality data from 21 populations of 11 Africa-dwelling primate species from the papionin tribe, occupying a wide range of environments, including equatorial, tropical, temperate and arid climates. We investigate (1) the environmental variations that influence the intensity of reproductive seasonality, and (2) the reproductive stage that is synchronized with increased resource availability. Our results demonstrate wide variation in the intensity of birth seasonality between and within species. Across multiple measures of climatic variation, we found rainfall unpredictability to be the only clear predictor of the intensity of reproductive seasonality across populations, i.e., greater year-to-year variation in the amount of rainfall was associated with lower to no reproductive seasonality. Finally, we identified diverse patterns of reproductive phenology, with the most seasonal breeders generally aligning lactation with the peak in resource availability while other populations show more diverse patterns, where conception, lactation or weaning can all be synchronized with maximal food availability. This study sheds new light on the extent and ecological drivers of flexible reproductive phenology in long-lived tropical mammals, and may even contribute to our understanding of why humans give birth year-round.

evolutionary biology↗

bioRxiv2024

Chloroquine attenuates hypoxia-mediated autophagy to curb thrombosis- an ex vivo and in vivo study

BackgroundHypoxia can trigger the activation of blood platelets, leading to thrombosis. If not addressed clinically, it can cause severe complications and fatal consequences as well. The current treatment regime for thrombosis is often palliative and includes long-term administration of anticoagulants, which has the risk of over-bleeding in injury and other secondary effects as well. This demands a deeper understanding of the process and exploration of an alternative therapeutic avenue. Interestingly, recent studies demonstrate that platelets though atypical and enucleated, possess components of autophagy machinery. This cellular homeostatic process though well-studied in non-platelet cells, is under-explored in platelets. MethodsIn this study, we report an activation of autophagy in rat-derived platelets cultured under physiologically relevant hypoxic condition (10% O2) ex vivo. Furthermore, autophagy was triggered in vivo when rats were exposed to hypobaric hypoxic conditions. Subsequently, restriction or surgical ligation of the inferior vena cava (IVC) was performed to induce thrombus formation. Post confirming the impact of autophagy induction on platelet functioning, it was inhibited, and then platelet activation and aggregation status were evaluated using light transmission aggregometry, flow cytometry, immunofluorescence and immunoblotting. ResultsHerein, we show that autophagy inhibition with the potent autophagy inhibitor-CQ, a repurposed FDA-approved drug, can significantly reduce platelet activation, both in ex vivo and in vivo settings. CQ withdrawal reversed the phenomenon indicating a dynamic effect. Thereafter, in flow restriction or surgical ligation model, interestingly, CQ-pre-treated rats showed reduced clotting ability. Importantly, CQ at the stipulated dose was found to be non-toxic to the tissues, as analyzed through histological staining. ConclusionThus, we propose that the repurpose of the FDA approved drug CQ can attenuate hypoxia-induced thrombosis through inhibition of autophagy and can be explored as an effective therapeutic alternative. HighlightsO_LIExposure of ex-vivo cultured platelets to physiologically relevant hypoxic condition (O2 concentration) can induce autophagy causing them to get activated and eventually aggregate. C_LIO_LIFDA approved drug chloroquine (CQ) is able to inhibit autophagy in anucleate cellular fragments, platelets, similar to nucleated cells and curb platelet functioning under hypoxic condition in both ex-vivo and in-vivo model. C_LIO_LIFlow restriction model mimicking deep vein thrombosis, emphasizes on the effect of CQ on impeding thrombus formation when used at a non-toxic dosage. C_LI

physiology↗

bioRxiv2024

Genome-Wide CRISPR-Cas9 Screening Identifies a Synergy between Hypomethylating Agents and SUMOylation Blockade in MDS/AML

Hypomethylating agents (HMAs) are frontline therapies effective at altering the natural course of Myelodysplastic Neoplasms (MDS) and Acute Myeloid Leukemia (AML). However, acquired resistance and treatment failure are hallmarks of HMA therapy. To address this clinical need, we performed a genome-wide CRISPR-Cas9 screen in a human MDS-derived cell line, MDS-L, and identified TOPORS as a highly ranked loss-of-function target that synergizes with HMAs, reducing leukemic burden and improving survival in xenograft models. We demonstrate that the depletion of TOPORS mediates sensitivity to HMAs by predisposing leukemic blasts to an impaired DNA damage response (DDR) accompanied by an accumulation of SUMOylated DNMT1 in HMA-treated TOPORS-depleted cells. Importantly, the combination of HMAs with targeting of TOPORS did not functionally impair healthy hematopoiesis. While inhibitors of TOPORS are currently unavailable, we show that inhibition of protein SUMOylation (upstream of TOPORS functions) with TAK-981 partially phenocopies HMA-sensitivity and DDR impairment. Overall, our data suggest that the combination of HMAs with the inhibition of SUMOylation or TOPORS demonstrates a favourable therapeutic index and is a rational treatment framework for High-Risk MDS (HR-MDS) or AML.

molecular biology↗

bioRxiv2024

Senolytic CAR T cells reverse aging-associated defects in intestinal regeneration and fitness

Intestinal stem cells (ISCs) drive the rapid regeneration of the gut epithelium to maintain organismal homeostasis. Aging, however, significantly reduces intestinal regenerative capacity. While cellular senescence is a key feature of the aging process, little is known about the in vivo effects of senescent cells on intestinal fitness. Here, we identify the accumulation of senescent cells in the aging gut and, by harnessing senolytic CAR T cells to eliminate them, we uncover their detrimental impact on epithelial integrity and overall intestinal homeostasis in natural aging, injury and colitis. Ablation of intestinal senescent cells with senolytic CAR T cells in vivo or in vitro is sufficient to promote the regenerative potential of aged ISCs. This intervention improves epithelial integrity and mucosal immune function. Overall, these results highlight the ability of senolytic CAR T cells to rejuvenate the intestinal niche and demonstrate the potential of targeted cell therapies to promote tissue regeneration in aging organisms.

cell biology↗

bioRxiv2024

The protein interactome of Escherichia coli carbohydrate metabolism.

Carbohydrate metabolism is strictly regulated by multiple mechanisms to meet cellular needs (i.e. energy production). Several mechanisms modulate the amount and activity of metabolic enzymes. Here, we investigate how carbohydrate metabolism (CHM) in E. coli is regulated by their interaction properties with other proteins and their quantities. We computationally analyze 378 protein-enzyme interactions (PEIs) potentially involved in carbohydrate metabolism. We identified 20 enzymes and 19 interactors that occur at stoichiometries that are highly likely to affect CHM and 174 interactions that are possibly conserved across thousands of bacteria. These PPIs are predicted to be of global importance, including pathogens. Author summaryIn systems biology, "big" data are used to reconstruct biological networks which are then investigated in detail to uncover their functional dynamics. Understanding functional dynamics finally helps in identifying biomarkers in the big networks. We apply this concept to the biological network which is a crosstalk of protein-protein interaction network and carbohydrate metabolic pathway in Escherichia coli K-12. We investigate if proteins regulate enzymes when they bind them and we predict that protein-enzyme interactions (PEIs) regulate carbohydrate metabolism in E. coli.

systems biology↗

bioRxiv2024

A comprehensive map of transient protein-protein interactions and their structural features in the E. coli 1-carbon metabolism pathway

Enzymes in a pathway often form metabolons through weak protein-protein interactions (PPI) that localize and protect labile metabolites. Due to their transient nature, the structural architecture of these enzyme assemblies has largely remained elusive, limiting our abilities to re-engineer novel metabolic pathways. Here we delineate a complete PPI map of 1225 interactions in the E. coli 1-carbon metabolism pathway using bimolecular fluorescence complementation that can capture transient interactions in vivo and show strong intra- and inter-pathway clusters within the folate and purine biosynthesis pathways. Scanning mutagenesis experiments along with AlphaFold predictions and meta-dynamics simulations reveal that most proteins use conserved "dedicated" interfaces distant from their active sites to interact with multiple partners. Diffusion-reaction simulations with shared interaction surfaces and realistic PPI networks reveal a dramatic speedup in metabolic pathway fluxes. Overall, this study sheds light on the fundamental features of metabolon biophysics and structural aspects of transient binary complexes. Significance statementEnzymes from the same metabolic pathway often form dynamic assemblies called metabolons, which channel metabolites as well as protect labile intermediates. Yet very little is known about their structural features or what makes these interactions transient. Paucity of such information has particularly affected our ability to engineer novel metabolic pathways, construct multi-scale mathematical models of cells, etc. We address this by obtaining a comprehensive map for 1225 interaction pairs in the essential 1-carbon metabolism pathway of E. coli. Using both high-throughput experiments and computation, we uncover that metabolon proteins tend to use a conserved dedicated interface to interact with their partners. These results shed light on structural and energetic aspects of PPI in metabolons at near atomic level of resolution.

biophysics↗

bioRxiv2024

S-nitrosylation of EZH2 at C329 and C700 interplay with PRC2 complex assembly, methyltransferase activity, and EZH2 stability to regulate endothelial functions

Nitric oxide (NO), a versatile bio-active molecule modulates cellular function through diverse mechanisms including S-nitrosylation of proteins. However, the role of this post-translational modification in regulating epigenetic pathways was very limitedly explored. Herein, we report that NO causes S-nitrosylation of selected cysteine residues of EZH2 in endothelial cells (EC) resulting in SUZ12 dissociation from EZH2 bound PRC2 complex, reduced methyltransferase activity, and diminished nuclear localization eventually hampering its stability. We detected a significant reduction in H3K27me3 upon exposure to NO as contributed by the early dissociation of SUZ12 from the PRC2 complex. Longer exposure to NO donors caused EZH2 cytosolic translocation, its ubiquitination, and further degradation primarily through the autophagosome-lysosome pathway. Through in silico S-nitrosylation prediction analysis and site-directed mutagenesis assay, we identified three cysteine residues namely at locations 260, 329, and 700 in EZH2 and further determined that S-nitrosylation of cysteine 329 induced EZH2 instability while S-nitrosylation of cysteine 700 abrogated EZH2s catalytic activity. A double mutant of EZH2 containing mutations at Cysteine 329 and 700 remained undeterred to NO exposure. Furthermore, reinforcing H3K27me3 in NO exposed EC through the use of an inhibitor of H3K27me3 demethylase, we confirmed a significant contribution of the EZH2-H3K27me3 axis in defining NO-mediated regulation of endothelial gene expression and migration. Molecular dynamics simulation study revealed SUZ12s inability in efficiently binding to the SAL domain of EZH2 upon S-nitrosylation of C329 and C700. Taken together, our study for the first-time reports that S-nitrosylation dependent regulation of EZH2 and its associated PRC2 complex influences endothelial homeostasis.

cell biology↗

bioRxiv2024

E41K Mutation Activates Brutons Tyrosine Kinase by Stabilizing an Inositol Hexakisphosphate Dependent Invisible Dimer

Brutons tyrosine kinase (BTK) regulates diverse cellular signaling of the innate and adaptive immune system in response to microbial pathogens. Downregulation or constitutive activation of BTK is reported in patients with autoimmune diseases or various B-cell leukemias. BTK is a multidomain protein tyrosine kinase that adopts an Src-like autoinhibited conformation maintained by the interaction between the kinase and PH-TH domains. The PH-TH domain plays a central role in regulating BTK function. The BTK is activated by binding to PIP3 at the plasma membrane upon stimulation by the B-cell receptor (BCR). The PIP3 binding allows dimerization of the PH-TH domain and subsequent transphosphorylation of the activation loop. Alternatively, a recent study shows that the multivalent T-cell-independent (TI) antigen induces BCR response by activating BTK independently of PIP3 binding. It was proposed that a transiently stable IP6-dependent PH-TH dimer may activate BTK during BCR activation by the TI antigens. However, no IP6-dependent PH-TH dimer has been identified yet. Here, we investigated a constitutively active PH-TH mutant (E41K) to determine if the elusive IP6-dependent PH-TH dimer exists. We showed that the constitutively active E41K mutation activates BTK by stabilizing the IP6-dependent PH-TH dimer. We observed that a downregulating mutation in the PH-TH domain (R28H) linked to X-linked agammaglobulinemia impairs BTK activation at the membrane and in the cytosol by preventing PH-TH dimerization. We conclude that the IP6 dynamically remodels the BTK active fraction between the membrane and cytoplasm. Stimulating with IP6 increases the cytosolic fraction of the activated BTK.

biochemistry↗

bioRxiv2023

High-resolution structures illuminate key principles underlying voltage and LRRC26 regulation of Slo1 channels

Multi-modal regulation of Slo1 channels by membrane voltage, intracellular calcium, and auxiliary subunits enables its pleiotropic physiological functions. Our understanding of how voltage impacts Slo1 conformational dynamics and the mechanisms by which auxiliary subunits, particularly of the LRRC (Leucine Rich Repeat containing) family of proteins, modulate its voltage gating remain unresolved. Here, we used single particle cryo-electron microscopy to determine structures of human Slo1 mutants which functionally stabilize the closed pore (F315A) or the activated voltage-sensor (R207A). Our structures, obtained under calcium-free conditions, reveal that a key step in voltage-sensing by Slo1 involves a rotameric flip of the voltage-sensing charges (R210 and R213) moving them by [~]6 [A] across a hydrophobic gasket. Next we obtained reconstructions of a complex of human Slo1 with the human LRRC26 ({gamma}1) subunit in absence of calcium. Together with extensive biochemical tests, we show that the extracellular domains of {gamma}1 form a ring of interlocked dominos that stabilizes the quaternary assembly of the complex and biases Slo1:{gamma}1 assembly towards high stoichiometric complexes. The transmembrane helix of {gamma}1 is kinked and tightly packed against the Slo1 voltage-sensor. We hypothesize that {gamma}1 subunits exert relatively small effects on early steps in voltage-gating but structurally stabilize non-S4 helices of Slo1 voltage-sensor which energetically facilitate conformational rearrangements that occur late in voltage stimulated transitions.

biophysics↗

bioRxiv2023

Nucleic acid sequence contributes to remodeler-mediated targeting of histone H2A.Z

The variant histone H2A.Z is inserted into nucleosomes immediately downstream of promoters and is important for transcription. The site-specific deposition of H2A.Z is catalyzed by SWR, a conserved chromatin remodeler with affinity for promoter-proximal nucleosome depleted regions (NDRs) and histone acetylation. By comparing the genomic distribution of H2A.Z in wild-type and SWR-deficient cells, we found that SWR is also responsible for depositing H2A.Z at thousands of non-canonical sites not directly linked to NDRs or histone acetylation. To understand the targeting mechanism of H2A.Z, we presented SWR with a library of nucleosomes isolated from yeast and characterized those preferred by SWR. We found that SWR prefers nucleosomes associated with intergenic over coding regions, especially when polyadenine tracks are present. Insertion of polyadenine sequences into recombinant nucleosomes near the H2A-H2B binding site stimulated the H2A.Z insertion activity of SWR. Therefore, the genome is encoded with information contributing to remodeler-mediated targeting of H2A.Z.

molecular biology↗

bioRxiv2023

Artificially inserted G-quadruplex DNA secondary structures induce long-distance chromatin activation

Although the role of G-quadruplex (G4) DNA structures has been suggested in chromosomal looping this was not tested directly. Here, to test causal function, an array of G4s, or control sequence that does not form G4s, were inserted within chromatin in cells. In vivo G4 formation of the inserted G4 sequence array, and not the control sequence, was confirmed using G4-selective antibody. Compared to the control insert, we observed a remarkable increase in the number of 3D chromatin looping interactions from the inserted G4 array. This was evident within the immediate topologically associated domain (TAD) and throughout the genome. Locally, recruitment of enhancer histone marks and the transcriptional coactivator p300/Acetylated-p300 increased in the G4-array, but not in the control insertion. Resulting promoter-enhancer interactions and gene activation were clear up to 5 Mb away from the insertion site. Together, these show the causal role of G4s in enhancer function and long-range chromatin interactions. Mechanisms of 3D topology are primarily based on DNA-bound architectural proteins that induce/stabilize long-range interactions. Involvement of the underlying intrinsic DNA sequence/structure in 3D looping shown here therefore throws new light on how long-range chromosomal interactions might be induced or maintained.

molecular biology↗

bioRxiv2023

An electromyography-based multi-muscle fatigue model to investigate operational task performance

We developed a multi-muscle fatigue model (MMFM) by incorporating electromyography (EMG)-based amplitude and frequency parameters, the fast-to-slow twitch muscle fiber ratio, a time multiplier to linearize the cumulative effect of time, and a muscle multiplier to standardize the combined effect of the number of muscles being considered. We validated the model by investigating fatigue development patterns of ten male subjects performing one sustained-till-exhaustion static and two repetitive dynamic tasks (low and high task difficulty levels) using 0.91 Kg and 2.72 Kg dumbbells. The results indicated that the MMFM was sensitive to fatigue-related neuromuscular changes and predicted shoulder joint fatigue accurately.

bioengineering↗

bioRxiv2023

Investigating the Role of Neck Muscle Activation and Damping Characteristics in Brain Injury Mechanism

PurposeThis study aimed to investigate the role of neck muscle activity and neck damping characteristics in traumatic brain injury (TBI) mechanisms. MethodsWe used a previously validated head-neck finite element (FE) model that incorporates various components such as scalp, skull, cerebrospinal fluid, brain, muscles, ligaments, cervical vertebrae, and intervertebral discs. Impact scenarios included a Golf ball impact, NBDL linear acceleration, and Zhangs linear and rotational accelerations. Three muscle activation strategies (no-activation, low-to-medium, and high activation levels) and two neck damping levels by perturbing intervertebral disc properties (high: hyper-viscoelastic and low: hyper-elastic) strategies were examined. We employed Head Injury Criterion (HIC), Brain Injury Criterion (BrIC), and maximum principal strain (MPS) as TBI measures. ResultsIncreased neck muscle activation consistently reduced the values of all TBI measures in Golf ball impact (HIC: 4%-7%, BrIC: 11%-25%, and MPS (occipital): 27%-50%) and NBDL study (HIC: 64%-69%, BrIC: 3%-9%, and MPS (occipital): 6%-19%) simulations. In Zhangs study, TBI metric values decreased with the increased muscle activation from no-activation to low-to-medium (HIC: 74%-83%, BrIC: 27%-27%, and MPS (occipital): 60%-90%) and then drastically increased with further increases to the high activation level (HIC: 288%-507%, BrIC: 1%-25%, and MPS (occipital): 23%-305%). Neck damping changes from low to high decreased all values of TBI metrics, particularly in Zhangs study (up to 40% reductions). ConclusionOur results underscore the pivotal role of neck muscle activation and neck damping in TBI mitigation and holds promise to advance effective TBI prevention and protection strategies for diverse applications.

bioengineering↗

bioRxiv2023

Effects of Firefighter Helmets on Cervical Intervertebral Kinematics: An OpenSim-Based Biomechanical Study

The assessment of cervical intervertebral kinematics can serve as the basis for understanding any degenerative changes in the cervical spine due to the prolonged wear of a heavyweight, imbalanced firefighting helmet. Therefore, this study aimed to analyze cervical intervertebral kinematics using OpenSim musculoskeletal modeling platform in order to provide much-needed insights of how the inertial properties of firefighter helmet affect cervical spinal mobility. A total of 36 firefighters (18 males and 18 females) were recruited to perform static and dynamic neck flexion, extension, and left and right lateral bending tasks for three conditions: 1) no-helmet, 2) US-style helmet with a comparatively superior center of mass (COM), and 3) European-style helmet with relatively higher mass but an inferior COM. Three custom-made OpenSim head-neck models were created to calculate cervical intervertebral kinematics for each helmet condition. Results showed that the helmet use significantly (p<0.001) affects neck and cervical spinal kinematics. Especially, the superior COM placement in the US-style helmet, despite its lighter weight, caused more pronounced kinematic changes and quicker attainment of peak flexion and extension angles compared to the European-style helmet across all cervical joints. Moreover, results also revealed discrepancies between OpenSim-derived neck and cervical range-of-motion and those reported in previous in-vivo studies. In conclusion, the present study underscores the importance of designing firefighter helmets with a lower profile (less superior COM) to enhance neck range of motion and minimize potential neck injuries.

bioengineering↗

bioRxiv2023

Dissecting the properties of circulating IgG against Group A Streptococcus through a combined systems antigenomics-serology workflow

Most individuals maintain circulating antibodies against various pathogenic bacteria as a consequence of previous exposures. However, it remains unclear to what extent these antibodies contribute to host protection. This knowledge gap is linked to the need for better methods to characterize antimicrobial polyclonal antibodies, including their antigen and epitope repertoires, subclass distribution, glycosylation status, and effector functions. Here, we showcase a generic mass spectrometry-based strategy that couples systems antigenomics and systems serology to characterize human antibodies directly in clinical samples. The method is based on automated affinity purification workflows coupled to an integrated suite of high-resolution MS-based quantitative, structural- and glyco-proteomics readouts. We focused on Streptococcus pyogenes (Group A Streptococcus; GAS), a major human pathogen still awaiting an approved vaccine. Our methodology reveals that both healthy and GAS infected individuals have circulating Immunoglobulin G (IgG) against a subset of genomically conserved streptococcal proteins, including numerous toxins and virulence factors. The antigen repertoire targeted by these antibodies was relatively constant across healthy individuals, but considerably changed in GAS bacteremia. Detailed analysis of the antigen-specific IgG indicates inter-individual variation regarding titers, subclass distributions, and Fc-signaling capacity, but not in epitope and Fc-glycosylation patterns. Importantly, we show that the IgG subclass has a major impact on the ability of GAS-antibodies to trigger immune signaling, in an antigen- and Fc receptor-specific fashion. Overall, these results uncover exceeding complexity in the properties of GAS-specific IgG, and showcase our methodology as high-throughput and flexible workflow to understand adaptive immune responses to bacterial pathogens. Significance statementMost people develop polyclonal antibodies against bacterial pathogens during infections but their structural and functional properties are poorly understood. Here, we showcase a combined systems antigenomics and systems serology strategy to quantify key antibody properties directly in clinical samples. We applied this method to characterize polyclonal antibody responses against Streptococcus pyogenes, a major human pathogen. We mapped the antigen and epitope landscape of anti-streptococcal antibodies circulating in healthy adult plasma, and their changes during blood infections. We further demonstrate the analytical power of our approach to resolve individual variations in the structure and effector functions of antigen-specific antibodies, including a dependency between immunoglobulin subclass and Fc-signaling capacity.

immunology↗

bioRxiv2023

Deconstructing the Mapper algorithm to extract richer topological and temporal features from functional neuroimaging data

Capturing and tracking large-scale brain activity dynamics holds the potential to deepen our understanding of cognition. Previously, tools from Topological Data Analysis, especially Mapper, have been successfully used to mine brain activity dynamics at the highest spatiotemporal resolutions. Even though it is a relatively established tool within the field of Topological Data Analysis, Mapper results are highly impacted by parameter selection. Given that non-invasive human neuroimaging data (e.g., from fMRI) is typically fraught with artifacts and no gold standards exist regarding "true" state transitions, we argue for a thorough examination of Mapper parameter choices to better reveal their impact. Using synthetic data (with known transition structure) and real fMRI data, we explore a variety of parameter choices for each Mapper step, thereby providing guidance and heuristics for the field. We also release our parameter-exploration toolbox as a software package to make it easier for scientists to investigate and apply Mapper on any dataset.

neuroscience↗