Biology subjects

Singh, A.

Publications and source records attributed to Singh, A..

At least 253 records · Page 14Linked to original sources

bioRxiv2024

Dynamics of gut colonization by commensal and pathogenic bacteria that adhere to the intestinal epithelium

Maintaining a healthy gut microbiome plays a critical role in avoiding gut-related pathologies. Bacterial adherence to the intestinal epithelium plays a vital role in niche establishment in the gut, as in vitro experiments and mathematical modeling suggest that adherence provides a strong competitive advantage over free-floating planktonic microbes. Currently, we lack the ability to study gut microbiome adherence in an in vivo model system. Through sampling natural populations of Caenorhabditis, we discovered three bacterial species that adhere to the intestinal epithelium of several wild Caenorhabditis isolates. When transferred to C. elegans, all three bacterial species colonized the entire anterior to posterior length of the intestine lumen. We isolated these bacterial species via in vitro growth or selective enrichment in the nematode gut and identified them as Lelliottia jeotgali, Candidatus Lumenectis limosiae, and Candidatus Enterosymbion pterelaium, the latter two representing new species. Adherent Ca. L. limosiae negatively affects host fitness, while Lelliottia jeotgali and Ca. E. pterelaium exhibited a neutral effect in our assays. We demonstrated that two of these species can actively proliferate in the intestine throughout the host lifespan, with Lelliottia jeotgali colonizing throughout the lumen simultaneously and Candidatus Lumenectis limosiae showing anterior-to-posterior directionality. In competition assays, animals pre-colonized with L. jeotgali significantly reduced colonization by pathogenic Ca. L. limosiae, but this effect was not seen when animals were colonized by both bacteria simultaneously. Strikingly, regardless of the colonization paradigm, populations exposed to both bacteria showed a near-identical mitigation of the pathogenic effects of Ca. L. limosiae. Altogether, these strains illustrate the capacity of microbiome bacteria to adhere, replicate, and establish a niche across the entire intestinal lumen in C. elegans and they present an opportunity to study bacterial adherence in the context of a whole, intact and transparent animal.

microbiology↗

bioRxiv2024

Wag31, a membrane tether, is crucial for lipid homeostasis in mycobacteria

The mycobacterial cytoskeletal protein Wag31 is necessary for maintaining cell shape and directing cellular growth and elongation. Wag31 has a characteristic N-terminal DivIVA-domain and a C-terminal coiled-coil domain. While the role of Wag31 in polar elongation is known, there is limited mechanistic insight on how it orchestrates growth and elongation. In this report, we delineate roles of the N- and C-terminal domains of Wag31 using genetics, state-of-the-art multi-omics, biochemical, and imaging approaches. We show that Wag31 predominantly interacts with several membrane-associated proteins involved in lipid metabolism, cell wall synthesis and division. Native levels of Wag31 are critical for the maintenance and distribution of membrane lipids. Both depletion and overexpression of Wag31 perturbs lipid homeostasis, leading to the formation of intracellular lipid inclusions (ILIs). Protein-lipid crosslinking and imaging studies reveal that purified Wag31 can bind and effectively tether Cardiolipin (CL)-containing liposomes. We further show that the tethering activity lies in the DivIVA-domain containing N-terminal of Wag31 while the C-terminal mediates protein-protein interactions of Wag31. Despite retaining its ability to interact with partner proteins, the DivIVA domain-deleted Wag31 mutant shows defects in liposome tethering in vitro and non-polar localization of CL in vivo, which eventually causes lethality. Our study suggests that membrane tethering licenses Wag31 to form scaffolds that help orchestrate protein-lipid and protein-protein interactions necessary for mycobacterial growth and survival.

microbiology↗

bioRxiv2024

Novel nanopore sequencing method for determining Human Papillomavirus integrations in tumors without the need for whole genome sequencing

Human papillomaviral (HPV) integrations into host human genome, a key event in cervical carcinogenesis, are currently mapped through laborious and expensive sequencing methodologies. We developed and validated a novel library preparation strategy for nanopore sequencing to generate long targeted reads with HPV and human chimeric sequences. Using this strategy, we validated known HPV integrations in HeLa (HPV18) and SiHa (HPV16) cell lines. We also mapped integration sites in five HPV+ cervical cancer patients, which were confirmed by whole genome and Sanger sequencing. Our nanopore-based method provides a precise and efficient strategy to capture HPV integrations crucial for understanding tumorigenesis.

genomics↗

bioRxiv2024

Heritable non-genetic phenotypes are enriched for stress responses as a form of bet hedging

During manufacturing batches, Chinese hamster ovary (CHO) cells encounter critical levels of environmental stressors such as ammonia, lactate, and osmolality accumulation that can significantly reduce cell health and productivity. It is therefore crucial that stress adaptation and resistance be factored into cell line development (CLD). In this study, we employee population-based transcriptomic and differential gene expression analysis on stress-induced CHO cells to identify biomarkers displaying both heritable and stress-responsive properties. Using this workflow, 199 genes displayed transcriptional variability characteristic of a bistable system that formed four network communities of co-fluctuating genes. These communities were enriched in genes related to the regulation of apoptotic processes and gene expression/metabolic pathways. Seven genes were identified as promising biomarkers for engineering a stress-resistant phenotype. Genetic engineering methods may be employed in the future to bias clonal populations for higher stress tolerance to manufacturing stress, therefore increasing cell health and productivity in at-scale bioreactors.

genomics↗

bioRxiv2024

CXCL10/CXCR3 Signaling Induces Neural Senescence and Cognitive Impairments

Chemokine receptors belong to the G-protein-coupled receptors family and multiple lines of emerging evidence suggest that several chemokines are elevated in aging associated with central nervous system disorders. Increased level of CXCL10 in central nervous system is reported in several neurodegenerative diseases, including Multiple sclerosis, Alzheimers disease, and Virus-associated dementia. We also observed significantly increased expression of CXCL10 and CXCR3 in the prefrontal cortex and hippocampus of aged C57BL/6J mice (12- and 18-month-old mice). This leads us to hypothesize that CXCL10, being a component of SASPs, may aggravate/perpetuate the brain aging process and, finally, neurodegenerative diseases. To test this hypothesis, we administered CXCL10 (intracerebroventricular: ICV, 0.5 pg/ hrs, 28 days) in 8-month-old C57BL/6J mice. We observed increased expression of senescent marker proteins p16INK4a, p21Cip1, p53 and decreased expression of pRB in the prefrontal cortex, which was blocked by CXCR3-specific antagonist AMG487. Furthermore, chronic infusion of CXCL10 induced learning and memory deficits in Y-maze, social recognition, contextual freeze tests and c-FOS expression in the prefrontal cortex. To further determine the specificity of CXCL10/CXCR3 signaling, we treated the primary cortical neuron (Days in vitro: DIV 7-8) with CXCL10 and found increased senescence in CXCR3 dependent fashion. Using RFP-EGFP-LC3-tagged transgenic mice, we also showed CXCL10/CXCR3 signaling attenuates autophagic flux in primary cortical neurons. Lastly, using a c-FOS-iRFP reporter, we observed that increased CXCL10/CXCR3 signaling impairs glutamatergic signaling in primary cortical neurons. These results support the hypothesis that increased CXCL10/CXCR3 facilitates brain aging and could be targeted for the management of aging-associated CNS disorders.

neuroscience↗

bioRxiv2024

Torsion is a Dynamic Regulator of DNA Replication Stalling and Reactivation

The inherent helical structure of DNA dictates that a replisome must rotate relative to DNA during replication, presenting inevitable topological challenges to replication. However, little is known about how the replisome progresses against torsional stress. Here, we developed a label-free, high-resolution, real-time assay to monitor replisome movement under torsion. We visualized the replisome rotation of DNA and determined how the replisome slows down under torsion. We found that while helicase or DNA polymerase (DNAP) individually is a weak torsional motor, the replisome composed of both enzymes is the most powerful DNA torsional motor studied to date. It generates [~] 22 pN{middle dot}nm of torque before stalling, twice the stall torque of E. coli RNA polymerase. Upon replisome stalling, the specific interaction between helicase and DNAP stabilizes the fork junction; without it, the fork can regress hundreds of base pairs. We also discovered that prolonged torsion-induced stalling inactivates the replisome. Surprisingly, DNAP exchange, mediated by the helicase, is highly effective in facilitating replication restart, but only if excess DNAP is present during stalling. Thus, helicase and DNA polymerase work synergistically as a powerful torsional motor, and their dynamic and fluid interactions are crucial for maintaining fork integrity under torsional stress. This work demonstrates that torsion is a strong regulator of DNA replication stalling and reactivation.

biophysics↗

bioRxiv2024

Structural insights into the RNA binding inhibitors of the C-terminal domain of the SARS-CoV-2 nucleocapsid

The SARS-CoV-2 nucleocapsid (N) protein is an essential structural element of the virion, playing a crucial role in enclosing the viral genome into a ribonucleoprotein (RNP) assembly, as well as viral replication and transmission. The C-terminal domain of the N-protein (N-CTD) is essential for encapsidation, contributing to the stabilization of the RNP complex. In a previous study, three inhibitors (ceftriaxone, cefuroxime, and ampicillin) were screened for their potential to disrupt the RNA packaging process by targeting the N-protein. However, the binding efficacy, mechanism of RNA binding inhibition, and molecular insights of binding with N-CTD remain unclear. In this study, we evaluated the binding efficacy of these inhibitors using isothermal titration calorimetry (ITC), revealing the affinity of ceftriaxone (18 {+/-} 1.3 M), cefuroxime (55 {+/-} 4.2 M), and ampicillin (28 {+/-} 1.2 M) with the N-CTD. Further inhibition assay and fluorescence polarisation assay demonstrated RNA binding inhibition, with IC50 ranging from 10.4 to 12.4 M and KD values between 24 and 32 M for the inhibitors. Additionally, we also determined the inhibitor-bound complex crystal structures of N-CTD-Ceftriaxone (2.0 [A]) and N-CTD-Ampicillin (2.2 [A]), along with the structure of apo N-CTD (1.4 [A]). These crystal structures revealed previously unobserved interaction sites involving residues K261, K266, R293, Q294, and W301 at the oligomerization interface and the predicted RNA-binding region of N-CTD. These findings provide valuable molecular insights into the inhibition of N-CTD, highlighting its potential as an underexplored but promising target for the development of novel antiviral agents against coronaviruses. HighlightsO_LIThe inhibitors ceftriaxone, cefuroxime, and ampicillin-demonstrated high-affinity binding to the C-terminal domain (N-CTD) of the SARS-CoV-2 nucleocapsid (N) protein, effectively disrupting the formation of the N-CTD-RNA complex. C_LIO_LIComplex crystal structures of N-CTD with ceftriaxone and ampicillin revealed previously unobserved distinct binding sites. C_LIO_LIStructures reveal how the selected inhibitors disrupt the oligomerization of N-CTD and hinder the RNA packaging process of the virus. C_LI

biophysics↗

bioRxiv2024

DNA Polymerase Locks Replication Fork Under Stress

Replication of DNA requires the parental DNA to be unwound to allow the genetic information to be faithfully duplicated by the replisome. While this function is usually shared by a host of proteins in the replisome, notably DNA polymerase (DNAP) and helicase, the consequence of DNAP synthesizing DNA while decoupled from helicase remains not well understood. The unwinding of downstream DNA poses significant stress to DNAP, and the interaction between DNAP and the replication fork may affect replication restart. In this work, we examined the consequences of DNAP working against the stress of the DNA replication fork. We found that prolonged exposure of DNAP to the stress of the replication fork inactivates replication. Surprisingly, replication inactivation was often accompanied by a strong DNAP interaction with the leading and lagging strands at the fork, locking the fork in place. We demonstrated that fork locking is a consequence of DNAP forward translocation, and the exonuclease activity of DNAP, which allows DNAP to move in reverse, is essential in protecting the fork from inactivation. Furthermore, we found the locking configuration is not reversible by the subsequent addition of helicase. Collectively, this study provides a deeper understanding of the DNAP-fork interaction and mechanism in keeping the replication fork active during replication stress.

biophysics↗

bioRxiv2024

Assembly of branched chain amino acid (BCAA) to toxic fibrils may be related to pathogenesis of Maple syrup urine disease (MSUD)

Inborn errors of metabolism (IEMs) are a group of diseases caused by mutations in single genes, leading to the buildup of metabolites that are typically toxic or disrupt normal cellular function. The etiological relation of metabolic disorders has been uncovered through the study of metabolite amyloids. Various metabolites that accumulate in IEMs have been reported to self-assemble into organized structures. These structures exhibit similar physicochemical properties as proteinaceous amyloid fibrils. In this context, our study illustrated the aggregation properties of Branched chain amino acid (BCAA) i.e. Isoleucine, Leucine and Valine that accumulate in Maple syrup urine disease (MSUD) to investigate their propensities to assemble into amyloid-like fibrils. The structural morphologies of BCAA were studied via. microscopic techniques like Scanning electron microscopy (SEM), optical microscopy and phase contrast microscopy. Further, characterization techniques were employed to understand the physicochemical properties of the self-assemblies and its underlying mechanism. The amyloid-like nature of these aggregates was confirmed using Thioflavin T (ThT) and Congo Red (CR) assays, indicating a possible cytotoxic effect. The MTT assay reveals BCAAs were cytotoxic and significantly decrease cell viability. Our study plays a key role in understanding the physicochemical properties of MSUD in association to amyloid disease, possibly paving the way for the development of therapeutic solutions in the future. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/616096v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@13f26daorg.highwire.dtl.DTLVardef@10fdef5org.highwire.dtl.DTLVardef@f6e1d7org.highwire.dtl.DTLVardef@64f608_HPS_FORMAT_FIGEXP M_FIG C_FIG The self-assembly of BCAA-Ile, Leu, Val was investigated and the findings indicate that their aggregation may follow an amyloidogenic pathway.

bioengineering↗

bioRxiv2024

BaMBo: An Annotated Bone Marrow Biopsy Dataset for Segmentation Task

Bone marrow examination has become increasingly important for the diagnosis and treatment of hematologic and other illnesses. The present methods for analyzing bone marrow biopsy samples involve subjective and inaccurate assessments by visual estimation by pathologists. Thus, there is a need to develop automated tools to assist in the analysis of bone marrow samples. However, there is a lack of publicly available standardized and high-quality datasets that can aid in the research and development of automated tools that can provide consistent and objective measurements. In this paper, we present a comprehensive Bone Marrow Biopsy (BaMBo) dataset consisting 185 semantic-segmented bone marrow biopsy images, specifically designed for the automated calculation of bone marrow cellularity. Our dataset comprises high-resolution, generalized images of bone marrow biopsies, each annotated with precise semantic segmentation of different haematological components. These components are divided into 4 classes: Bony trabeculae, adipocytes, cellular region and Background (BG). The annotations were performed with the help of two experienced hematopathologists that were supported by state-of-the-art Deep Learning (DL) models and image processing techniques. We then used our dataset to train a custom U-Net based DL model that performs multi-class semantic segmentation of the images (Dice Score: 0.831 {+/-} 0.099) and predicts the cellularity of these images with an error of 5.9% {+/-} 8.8%. This shows the applicability of our data for future research in this domain. Our code is available at https://github.com/AI-in-Medicine-IIT-Ropar/BaMbo-Bone-Marrow-Biopsy.

pathology↗

bioRxiv2024

Bacterial cell size modulation along the growth curve across nutrient conditions

Under stable growth conditions, bacteria maintain cell size homeostasis through coordinated elongation and division. However, fluctuations in nutrient availability result in dynamic regulation of the target cell size. Using microscopy imaging and mathematical modelling, we examine how bacterial cell volume changes over the growth curve in response to nutrient conditions. We find that two rod-shaped bacteria, Escherichia coli and Salmonella enterica, exhibit similar cell volume distributions in stationary phase cultures irrespective of growth media. Cell resuspension in rich media results in a transient peak with a five-fold increase in cell volume {approx} 2h after resuspension. This maximum cell volume, which depends on nutrient composition, subsequently decreases to the stationary phase cell size. Continuous nutrient supply sustains the maximum volume. In poor nutrient conditions, cell volume shows minimal changes over the growth curve, but a markedly decreased cell width compared to other conditions. The observed cell volume dynamics translate into non-monotonic dynamics in the ratio between biomass (optical density) and cell number (colony-forming units), highlighting their non-linear relationship. Our findings support a heuristic model comparing modulation of cell division relative to growth across nutrient conditions and providing novel insight into the mechanisms of cell size control under dynamic environmental conditions.

microbiology↗

bioRxiv2024

Sca-1 expression depicts pro-inflammatory murine neutrophils under steady state and pathological conditions

Neutrophils play a crucial role in various pathophysiological conditions, yet targeting them for therapeutic intervention has been discouraged due to the associated risk of infections. Thus, identification of neutrophil subsets and their involvement in inflammatory conditions is warranted for targeted therapeutic strategies. This study, through screening of surface proteins on neutrophils isolated from different tissue microenvironments, identified a distinct neutrophil subset, CD11b+Ly6G+Sca1+ neutrophils, expressing Stem cell antigen-1 (Sca-1). Interestingly, these Sca1pos neutrophils were more abundant in the liver than BM, blood, and lungs. Further analysis revealed that Sca1pos neutrophils are mature and activated with enhanced effector functions, including superoxide generation, phagocytosis, degranulation, and NETosis. Tracing studies demonstrated ageing-independent characteristics of Sca1pos neutrophils. Remarkably, Sca1pos pro-inflammatory neutrophils promote T cell proliferation through ROS, while inhibition of Sca-1 restores T cell proliferation and ROS generation. Intriguingly, inflammatory as well as metabolic cues induce the transition of conventional neutrophils (Sca1neg) to Sca1pos neutrophils and differentiation of progenitors (granulocyte monocyte progenitors, GMPs) into Sca1pos neutrophils. Furthermore, in vivo models of acute inflammation, peritonitis, and chronic inflammatory condition, non-alcoholic steatohepatitis (NASH), exhibit an increase of Sca1pos neutrophils at inflammatory sites, while the pharmacological approach using NAC specifically mitigates the expansion of these pro-inflammatory neutrophils. Collectively, our findings unveil a novel subset of Sca1pos neutrophils with implications for inflammation. Significance StatementNeutrophilic inflammation remains the leading driver in infectious and inflammatory diseases. Targeting neutrophil populations remained un-recommended due to hampering the immunological functions of neutrophils. The heterogeneity of neutrophils provides the perspective to target altered neutrophil subsets, but subtle changes defining neutrophil subsets make it complex and ambiguous. Our study identified abundant expression of Sca1on distinct neutrophils under steady state and inflammation. Thus, we reported previously undefined Sca1pos pro-inflammatory neutrophil subsets and elucidated their regulation. This study further established their involvement in acute and chronic inflammatory conditions. This understanding may further pave the way toward targeting specific neutrophil subsets in pathologies characterized by neutrophilic inflammation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/613221v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@62f3eaorg.highwire.dtl.DTLVardef@7baed3org.highwire.dtl.DTLVardef@12da63org.highwire.dtl.DTLVardef@1bfcce9_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LICD11b+Ly6G+Sca1+ neutrophil subset identified with <1% presence in BM and >40% frequency in the liver. C_LIO_LIThese neutrophils are mature and activated, demonstrating enhanced effector functions. C_LIO_LISca1pos neutrophils promote T cell proliferation and display pro-inflammatory characteristics. C_LIO_LIConventional Sca1neg neutrophils transition into Sca1pos neutrophils in response to inflammatory signals, while progenitors undergo differentiation. C_LIO_LIBoth acute and chronic inflammatory models show the expansion of CD11b+Ly6G+Sca1+ neutrophils. C_LI

immunology↗

bioRxiv2024

A Generalized Adder mechanism for Cell Size Homeostasis: Implications for Stochastic Dynamics of Clonal Proliferation

Measurements of cell size dynamics have revealed phenomeno-logical principles by which individual cells control their size across diverse organisms. One of the emerging paradigms of cell size homeostasis is the adder, where the cell cycle duration is established such that the cell size increase from birth to division is independent of the newborn cell size. We provide a mechanistic formulation of the adder considering that cell size follows any arbitrary non-exponential growth law. Our results show that the main requirement to obtain an adder regardless of the growth law (the time derivative of cell size) is that cell cycle regulators are produced at a rate proportional to the growth law and cell division is triggered when these molecules reach a prescribed threshold level. Among the implications of this generalized adder, we investigate fluctuations in the proliferation of single-cell derived colonies. Considering exponential cell size growth, random fluctuations in clonal size show a transient increase and then eventually decay to zero over time (i.e., clonal populations become asymptotically more similar). In contrast, several forms of non-exponential cell size dynamics (with adder-based cell size control) yield qualitatively different results: clonal size fluctuations monotonically increase over time reaching a non-zero value. These results characterize the interplay between cell size homeostasis at the single-cell level and clonal proliferation at the population level, explaining the broad fluctuations in clonal sizes seen in barcoded human cell lines.

systems biology↗

bioRxiv2024

Noisy hemoglobin consumption by erythrocytic Plasmodium falciparum parasites: origins and possible implications

Non-genetic cell-to-cell phenotypic differences can significantly impact pathogen physiol-ogy and virulence, leading to unexpected phenomena such as antibiotic persistence. Here, we introduce the role of such non-genetic phenotypic differences in the host, with a focus on hemoglobin consumption by Plasmodium falciparum during the erythrocytic stage of parasite development. Through imaging, we quantified the substantial variability in hemoglobin (Hb) concentration among uninfected red blood cells (RBCs), and subse-quently measured the rate of Hb consumption by parasites at different stages of their life cycle. This revealed a similarly significant variability among different infected RBCs. By employing a mathematical model, we demonstrated that this variability in Hb consumption can be attributed to non-genetic differences in host RBCs, marking the first evidence of this phenomenon in malaria parasite physiology. These findings underscore the im-portance of incorporating non-genetic host variability into models of disease progression and treatment strategies for malaria and potentially other pathogen-related diseases.

biophysics↗

bioRxiv2024

DuReS: An R package for denoising experimental tandem mass spectrometry-based metabolomics data

Mass spectrometry-based untargeted metabolomics is a powerful technique for profiling small molecules in biological samples, yet accurate metabolite identification remains challenging. One of the primary obstacles in processing tandem mass spectrometry data is the prevalence of random noise peaks, which can result in false annotations and necessitate labor-intensive verification. A common method for removing noise from MS/MS spectra is intensity thresholding, where low-intensity peaks are discarded based on a user-defined cutoff or by analyzing the top "N" most intense peaks. However, determining an optimal threshold is often dataset-specific and may retain many noisy peaks. In this study, we hypothesize that true signal peaks consistently recur across replicate MS/MS spectra generated from the same precursor ion, unlike random noise. An optimal recurrence frequency of 0.12 (95% CI: 0.087-0.15) was derived using an open-source metabolomics dataset, which enhanced the dot product score between the experimental and library spectra by 66% post-denoising and resulted in a median signal and noise reduction of 5.83% and 99.07%, respectively. Validated across multiple metabolomics datasets, our denoising workflow significantly improved spectral matching metrics, leading to more accurate annotations and fewer false positives. Available freely as an R package, Denoising Using Replicate Spectra (DuReS) (https://github.com/BiosystemEngineeringLab-IITB/dures) is designed to remove noise while retaining diagnostically significant peaks efficiently. It accepts mzML files and feature lists from standard global untargeted metabolomics analysis software as input, enabling users to seamlessly integrate the denoising pipeline into their workflow without additional data manipulation.

bioinformatics↗

bioRxiv2024

PANOMIQ: A Unified Approach to Whole-Genome, Exome, and Microbiome Data Analysis

The integration of whole-genome sequencing (WGS), whole-exome sequencing (WES), and microbiome analysis has become essential for advancing our understanding of complex biological systems. However, the fragmented nature of current analytical tools often complicates the process, leading to inefficiencies and potential data loss. To address this challenge, we present PANOMIQ, a comprehensive software solution that unifies the analysis of WGS, WES, and microbiome data into a single, streamlined pipeline. PANOMIQ is designed to facilitate the entire analysis process from raw data to interpretable results. It is the fastest algorithm that can achieve results much more quickly compared to traditional pipeline approaches of WGS and WES analysis. It incorporates advanced algorithms for high-accuracy variant calling in both WGS and WES, along with robust tools for characterizing microbial communities. The softwares modular architecture allows for seamless integration of these diverse data types, enabling researchers to uncover complex interactions between host genomics and microbiomes. In this study, we demonstrate the capabilities of PANOMIQ by applying it to a series of datasets encompassing a wide range of applications, including disease association studies and environmental microbiome profiling. Our results highlight PANOMIQs ability to deliver comprehensive insights, significantly reducing the time and computational resources required for multi-omic analysis. By providing a unified platform for WGS, WES, and microbiome analysis, PANOMIQ offers a powerful tool for researchers aiming to explore the full spectrum of genomic and microbial diversity. This software not only simplifies the analytical workflow but also enhances the depth of biological interpretation, paving the way for more integrated and holistic studies in genomics and microbiology.

bioinformatics↗

bioRxiv2024

Timing of starvation determines its effects on susceptibility to infection in Drosophila melanogaster females independent of host evolutionary history

An organisms susceptibility to pathogens is contingent on various environmental factors, including the availability of nutrition. Starvation can alter host susceptibility to infections, either directly via depletion of resources essential for proper functioning of the immune system, or indirectly via the various physiological changes it induces within the host body. We tested if the susceptibility of Drosophila melanogaster populations to Enterococcus faecalis infection is affected by (a) whether the hosts are starved before or after the infection, and (b) the evolutionary history of the host. Hosts from laboratory fly populations that have been experimentally evolved to be more resistant to E. faecalis, and their corresponding control populations, were subjected to infection with or without being starved prior to and after being infected. We found that the effect of starvation on susceptibility to E. faecalis changed with the timing of starvation: starvation after infection improved survival of infected hosts, irrespective of how they were treated before infection, while starving only prior to infection (and not after) compromised post-infection survival. The changes in infection susceptibility were uniform in both the evolved and the control populations, suggesting that the effects of starvation are not dependent on pre-existing resistance to the infecting pathogen.

evolutionary biology↗

bioRxiv2024

Going New Places: Successful Adaptation and Genomic Integrity of Grain Amaranth in India

Global climate change will impact worldwide crop yields, requiring shifts and adaptation of crop varieties. The recent global spread of crops across different continents shows how plants successfully colonized new environments. One such spread is the introduction of the nutritious pseudocereal amaranth to India. Grain amaranth has been domesticated over 6,000 years ago in three different regions of the Americas and was introduced to India approximately 500 years ago. Nowadays numerous local landraces grow throughout the countrys wide climatic conditions. We investigate the introduction of grain amaranth to India to understand the factors allowing successful establishment of crops to novel environments, using whole genome sequencing of almost 200 accessions from India and more than 100 accessions from the crops native distribution. We find comparable levels of genetic diversity in the Americas and in India, despite the likely population bottleneck during the introduction to India. Surprisingly, the three grain amaranth species that were introduced do not show signs of gene-flow in India, while gene-flow in the Americas was high during the domestication of the crops. Correspondingly, the genetic differentiation between grain species was higher within India than in the native range, indicating a strong isolation between otherwise interbreeding populations. The reconstruction of the population history through demographic modelling of different scenarios suggested rapid expansion in the Indian population but a strong bottleneck in the native population, explaining the comparable diversity and isolation. We identified genomic loci under selection and associated with the climate in India that potentially enabled the adaptation to the new environment. These loci are predicted to provide an advantage under future climate scenarios, even in the native range. Our results suggest that introduced crops can act as reservoirs of genetic diversity, providing additional adaptive potential and resilience to future environmental change.

evolutionary biology↗