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Dutta, A.

Publications and source records attributed to Dutta, A..

At least 55 records · Page 3Linked to original sources
bioRxiv2023

A chemically-induced attenuated strain of Candida albicans generates robust protective immune response and prevents systemic candidiasis development

Despite current antifungal therapy, invasive candidiasis causes >40% mortality in immunocompromised individuals. Therefore, developing an antifungal vaccine is a priority. Here, we could for the first time successfully attenuate the virulence of Candida albicans by treating it with a fungistatic dosage of EDTA and demonstrate it to be a potential live whole cell vaccine by using murine models of systemic candidiasis. EDTA inhibited the growth and biofilm formation of C. albicans. RNA-seq analyses of EDTA-treated cells (CAET) revealed that genes mostly involved in metal homeostasis and ribosome biogenesis were up- and down-regulated, respectively. Consequently, a bulky cell wall with elevated levels of mannan and {beta}-glucan, and reduced levels of total monosomes and polysomes were observed. CAET was eliminated faster than the untreated strain (Ca) as found by differential fungal burden in the vital organs of the mice. Higher monocytes, granulocytes, and platelet counts were detected in Ca-vs CAET-challenged mice. While hyper-inflammation and immunosuppression caused the killing of Ca-challenged mice, a critical balance of pro- and anti-inflammatory cytokines-mediated immune responses are the likely reasons for the protective immunity in CAET-infected mice.

microbiology↗
bioRxiv2023

Bacterial pore-forming toxin pneumolysin drives pathogenicity through shed toxin-loaded host extracellular vesicles

Streptococcus pneumoniae is a global priority respiratory pathogen that kills over a million people annually and produces the pore-forming cytotoxin, pneumolysin (PLY). Host cells expel membrane assembled toxin by shedding microvesicles, but the composition and pathophysiological sequelae of the toxin-induced host extracellular vesicles (EVs) are unknown. Here, we found that EVs shed from PLY-challenged monocytes (PLY-EVs) harbor membrane-bound toxin that induced cytotoxicity upon fusion with recipient cells. EVs from human monocytes challenged with recombinant PLY as well as PLY-expressing pneumococcal strains, but not the isogenic PLY mutant, primed dendritic cells and evoked higher pro-inflammatory cytokines upon infection. Proteomic analysis revealed that PLY-EVs are enriched for key antimicrobial and inflammatory host proteins such as IFI16, NLRC4, PTX3 and MMP9. In vivo, zebrafish and mice administered with PLY-EVs showed mortality, pericardial edema, tissue damage and inflammation. Our findings show that host EVs bearing the cytotoxin PLY constitute a previously unexplored mechanism of pneumococcal pathogenesis.

microbiology↗
bioRxiv2023

Phosphate starvation regulates cellulose synthesis to modify root growth

In the model plant Arabidopsis thaliana, the absence of the essential macro-nutrient phosphate reduces primary root growth through decreased cell division and elongation, requiring alterations to the polysaccharide-rich cell wall surrounding the cells. Despite its significance, the regulation of cell wall synthesis in response to low phosphate levels is not well understood. In this study, we show that plants increase cellulose synthesis in roots under limiting phosphate conditions, which leads to changes in the thickness and structure of the cell wall. These changes contribute to the reduced growth of primary roots in low phosphate conditions. Furthermore, we found that the cellulose synthase complex activity at the plasma membrane increases during phosphate deficiency. Moreover, we show that this increase in the activity of the cellulose synthase complex is likely due to alterations in the phosphorylation status of cellulose synthases in low phosphate conditions. Specifically, phosphorylation of CELLULOSE SYNTHASE 1 at the S688 site decreases in low phosphate conditions. Phosphomimic versions of CELLULOSE SYNTHASE 1 with an S688E mutation showed significantly reduced cellulose induction and primary root length changes in low phosphate conditions. Protein structure modelling suggests that the phosphorylation status of S688 in CELLULOSE SYNTHASE 1 could play a role in stabilizing and activating the cellulose synthase complex. This mechanistic understanding of root growth regulation under limiting phosphate conditions provides potential strategies for changing root responses to soil phosphate content.

plant biology↗
bioRxiv2023

Gestures Of Hunger: Uncovering Intentional Gestural Communication In Free-Ranging Hanuman Langurs

Contrary to previous beliefs, intentional gestural communication (IGC) is not exclusive to the hominoid lineage but is also present in other non-human primates. Here, we report the presence of IGC among free-ranging Hanuman langur troop in Dakshineswar, West Bengal, India. These langurs exhibit a food-requesting behaviour wherein they use several gestures to communicate with the humans nearby. Moreover, they can also assess the recipients mental state and persistently check if the signal (food request) has been received, waiting until they receive the desired food item. We have identified eight begging gestures used by langurs of all ages, except infants. The most common gesture is by holding cloth (BGc), but provocation-initiated begging (BGpi) and begging by embracing legs (BGe) efficiently direct these events to its success. The frequency of successful begging events is higher in the evening due to increased human interactions. Our findings suggest that ontogenetic ritualization might be at play here among these troop members as this gestural communication has been learned through imitation and reinforced by the reward of receiving food. Moreover, these successful begging events serve as an effective foraging strategy for urban-adapted langurs, allowing them to acquire high-calorie processed food items within a human-modified urban ecosystem.

animal behavior and cognition↗
bioRxiv2023

Development of a Quorum-Sensing Based Bacterial GMO for Targeted Treatment of Bovine Mastitis.

Bovine mastitis, a prevalent and costly disease affecting dairy cows, severely impacts milk production, quality, and cow health and poses significant challenges to the dairy industry worldwide. Traditional treatment strategies relying on antibiotics face concerns of antibiotic resistance and residual antibiotic residues in dairy products. Therefore, there is an urgent need for innovative and sustainable approaches. Our study undertakes a preliminary investigation into the formulation and efficacy of a GMO-based antibiotic-free treatment in fighting Bovine mastitis. We propose to use the bioengineered defensin Nisin PV as the antimicrobial to specifically target the causative pathogen Staphylococcus aureus. To disrupt the biofilm formation, we have leveraged the potency of DNaseI. By hacking the quorum sensing technique of Staphylococcus aureus, our proposed genetically modified bacteria would sense the presence of pathogens and initiate their eradication by producing Nisin PV and DNaseI. Results show the efficacy of DNase I against bacterial biofilm formation, in addition to the efficacy of our proposed sensor, which is based on the agr quorum sensing system of Staphylococcus aureus, a major cause of bovine mastitis. Molecular dynamics and simulations show that our choice of the bacterial defensin, Nisin PV, is less susceptible to cleavage by bacterial strains resistant to the native bacteriocin Nisin A. Additionally, we theoretically propose a lysis-based kill switch to ensure the release of the therapeutic components. The solution proposed in this study has the potential to offer a sustainable and effective alternative to antibiotic-based treatments. Implementation of bioengineered defensins could reduce disease incidence, minimize economic losses, and promote responsible antimicrobial stewardship in the dairy industry.

synthetic biology↗
bioRxiv2023

Biomechanical comparison of plate materials and designs for subcondylar fracture fixation: An in silico assessment

Mandibular subcondylar fractures present challenges in fixation due to high complication rates and the uncertainty in selecting optimal plate design and material. Previous computational studies have primarily relied on simplified models, point loading, and plate-only analyses. This study examines the combined influence of fixation plate design and material properties on fracture stability, with interfragmentary displacement as a key indicator of post-surgical stability. A finite element approach implemented in ANSYS Mechanical APDL v2022 R2, incorporating soft tissues such as the periodontal ligament, was employed to assess fixation stability using five materials - Nitinol, Magnesium alloys, Titanium alloys (Ti-6Al-4V and Ti-29Nb-13Ta-4.6Zr), and Stainless Steel 316L - across four plate designs under ipsilateral and contralateral molar clenching simulated using physiologically-mimetic muscle forces. Results showed a reduction in mandibular strain (up to 4% from around 1635 {micro}{varepsilon} to 1569 {micro}{varepsilon}) with increase in the plate stiffness during ipsilateral clenching, while for contralateral clenching, this trend (up to 5.4% from around 1482 {micro}{varepsilon} to 1402 {micro}{varepsilon}) was observed only for double mini and lambda plates due to enhanced resistance to bending moments from additional screw placement. Among designs, the double mini plate demonstrated the greatest reduction in the interfragmentary gap (by 77% during ipsilateral clenching; by 58% during contralateral clenching) and emerged as the most stable option across materials. Regarding materials, Titanium alloys (TNTZ and Ti-6Al-4V) were mechanically preferable, demonstrating higher safety margins based on factory of safety (FoS) ratios (TNTZ: FoS 5.57 ipsilateral, 3.21 contralateral; Ti-6Al-4V: FoS 5.05 ipsilateral, 2.98 contralateral), indicating reduced risk of yielding under functional loading. These findings underscore the critical interplay between screw configuration, material selection, and loading conditions, offering valuable guidance for implant design optimization.

bioengineering↗
bioRxiv2023

Systematic characterization of therapeutic vulnerabilities in Multiple Myeloma with Amp1q reveals increased sensitivity to the combination of MCL1 and PI3K inhibitors

The development of targeted therapy for patients with Multiple Myeloma (MM) is hampered by the low frequency of actionable genetic abnormalities. Gain or amplification of chr1q (Amp1q) is the most frequent arm-level copy number gain in patients with MM, and it is associated with higher risk of progression and death despite recent advances in therapeutics. Thus, developing targeted therapy for patients with MM and Amp1q stands to benefit a large portion of patients in need of more effective management. Here, we employed large-scale dependency screens and drug screens to systematically characterize the therapeutic vulnerabilities of MM with Amp1q and showed increased sensitivity to the combination of MCL1 and PI3K inhibitors. Using single-cell RNA sequencing, we compared subclones with and without Amp1q within the same patient tumors and showed that Amp1q is associated with higher levels of MCL1 and the PI3K pathway. Furthermore, by isolating isogenic clones with different copy number for part of the chr1q arm, we showed increased sensitivity to MCL1 and PI3K inhibitors with arm-level gain. Lastly, we demonstrated synergy between MCL1 and PI3K inhibitors and dissected their mechanism of action in MM with Amp1q.

cancer biology↗
bioRxiv2023

Integrative analysis of DNA replication origins and ORC binding sites in human cells reveals a lack of overlap between them

Based on experimentally determined average inter-origin distances of [~]100 kb, DNA replication initiates from [~]50,000 origins on human chromosomes in each cell cycle. The origins are believed to be specified by binding of factors like the Origin Recognition Complex (ORC) or CTCF or other features like G-quadruplexes. We have performed an integrative analysis of 113 genome-wide human origin profiles (from five different techniques) and 5 ORC-binding profiles to critically evaluate whether the most reproducible origins are specified by these features. Out of [~]7.5 million union origins identified by all datasets, only 0.27% were reproducibly obtained in at least 20 independent SNS-seq datasets and contained in initiation zones identified by each of three other techniques (20,250 shared origins), suggesting extensive variability in origin usage and identification. 21% of the shared origins overlap with transcriptional promoters, posing a conundrum. Although the shared origins overlap more than union origins with constitutive CTCF binding sites, G-quadruplex sites and activating histone marks, these overlaps are comparable or less than that of known Transcription Start Sites, so that these features could be enriched in origins because of the overlap of origins with epigenetically open, promoter-like sequences. Only 6.4% of the 20,250 shared origins were within 1 kb from any of the [~]13,000 reproducible ORC binding sites in human cancer cells, and only 4.5% were within 1 kb of the [~]11,000 union MCM2-7 binding sites in contrast to the nearly 100% overlap in the two comparisons in the yeast, S. cerevisiae. Thus, in human cancer cell lines, replication origins appear to be specified by highly variable stochastic events dependent on the high epigenetic accessibility around promoters, without extensive overlap between the most reproducible origins and currently known ORC- or MCM-binding sites.

genomics↗
bioRxiv2023

Differential expression of miRNAs between Young-Onset and Late-Onset Indian colorectal carcinoma patients

Early-Onset Colorectal Carcinoma (EOCRC) is a growing concern as reports indicate a worldwide increase in the incidence of CRC among young adults (<50 years old). In an effort to understand the different mode of pathogenesis in young-onset CRC, we performed a pilot study wherein we looked at colorectal tumors from both young (< 50 years old) and old patients (>55 years old) and screened them to eliminate tumors positive for Microsatellite Instability (MSI) and showing activation of the Wnt pathway, known canonical factors in CRC pathogenesis. RNA isolated from EOCRC and Late-Onset (LOCRC) tumors and paired normal tissues without MSI, nuclear {beta}-catenin and APC mutations were sent for small RNA seq to identify miRNA alterations between the two subsets. Comparative analysis revealed differential expression of 23 miRNAs specific to EOCRC and 11 miRNAs specific to LOCRC. We validated the top 10 EOCRC DEMs in TCGA-COAD cohorts followed by validation in additional EOCRC and LOCRC cohorts. Our integrated analysis revealed upregulation of hsa-miR-1247-3p, hsa-miR-148a-3p and hsa-miR-27a-5p and downregulation of hsa-miR-326 between the two subsets. Experimentally validated targets of the above miRNAs were compared with differentially expressed genes in the TCGA dataset to identify targets with physiological significance in EOCRC development. Our analysis revealed downregulation of epithelial gene expression and intercellular junction proteins potentially leading to dissolution of epithelial intercellular junctions in EOCRC development and EMT progression. Upregulated targets included genes whose expression have been reported to correlate with CRC tumor invasion, liver metastasis, disease recurrence and poor prognosis.

cancer biology↗
bioRxiv2023

A robust and flexible deep-learning workflow for animal tracking

Developments in automated animal behavioural analysis software are increasing the efficiency of data collection and improving the standardization of behavioural measurements. There are now several open-source tools for tracking laboratory animals, but often these are only accurate under limited conditions (e.g. uniform lighting and background, uncluttered scenes, unobstructed focal animal). Tracking fish presents a particular challenge for these tools because movement at the waters surface introduces significant noise. Partial occlusion of the focal animal can also be troublesome, particularly when tracking the whole organism. But identifying the position of an animal is only part of the task - analysing the movement of the animal relative to their environment and experimental context is often what provides information about their behaviour. Therefore, the automated detection of physical objects and boundaries would also be beneficial, but this feature is not commonly incorporated into existing tracking software. Here we describe a video processing method that uses a range of computer vision algorithms (e.g. object detector and tracker, optical flow, parallel plane homology) and computational geometry techniques (e.g. Voronoi tessellation) to analyse the movement behaviour of fish in response to experimental stimuli. A behavioural experiment, which involved tracking a fishs trajectory through a field of obstacles, motivated our development of a set of tools that: (1) measure an animals trajectory, (2) record obstacle position, and (3) detect when the fish passed through virtual gates between adjacent obstacles and/or the aquarium wall. We have introduced a novel Detect+Track approach that significantly enhances the accuracy and robustness of animal tracking, overcoming some of the limitations of existing tools and providing a more reliable solution for complex experimental conditions. Our workflow is divided into several discrete steps, and provides a set of modular software building blocks that can be adapted to analyse other experimental designs. A detailed tutorial is provided, together with all the data and code required to reproduce our results.

animal behavior and cognition↗
bioRxiv2023

Increase in primary cilia number and length upon VDAC1 depletion contributes to attenuated proliferation of cancer cells

Primary cilia (PCs) that are present in most human cells and perform sensory function or signal transduction are lost in many solid tumors. Previously, we identified VDAC1, best known to regulate mitochondrial bioenergetics, to negatively regulate ciliogenesis. Here, we show that downregulation of VDAC1 in pancreatic cancer-derived Panc1 and glioblastoma-derived U-87 cells significantly increased ciliation. Those PCs were remarkably longer than the control cells. Such increased ciliation inhibited cell cycle, which contributed to reduced proliferation of these cells. VDAC1-depletion also led to longer PCs in quiescent RPE1 cells. Therefore, serum-induced PC disassembly was slower in VDAC1-depleted RPE1 cells. Overall, this study reiterates the importance of VDAC1 in modulating tumorigenesis, due to its novel role in regulating PC length and disassembly.

cell biology↗
bioRxiv2023

Left or right: Handedness in free-ranging Hanuman langurs (Semnopithecus entellus) residing in an urban ecosystem.

Examining manual lateralization (handedness) in nonhuman primates might be an interesting approach to gaining insight into the evolution of asymmetry in humans. Moreover, handedness could also reflect the effect of environmental alterations on the free-ranging animals who are forced to live with anthropogenic interferences. Despite addressing the handedness among monkeys and apes, only a few studies have focused on these free-ranging urban-adapted nonhuman primates, which could challenge our perception of habitat loss and deforestation. Here, we conducted 193 field-based experimental trials with two experimental tasks, one unimanual (simple reaching) and one bimanual (tube task) to explore manual lateralization in a highly human-provisioned group of free-ranging Hanuman langur (Semnopithecus entellus). Experimental outcomes revealed an asymmetrical hand-use distribution, with a bias toward the left hand. As bimanual tasks evoked a higher degree of lateralization, these tasks seem to be more suited to study manual laterality, and our results also highlight the significance of experimental tasks in establishing hand preference in langurs. Furthermore, this study also reveals that such lateralization developed with age as adults distinctly displayed their preference toward left-hand usage in contrast to juveniles and subadults who used both hands comparably. Mostly considered to be arboreal, the langurs of our study group spend a considerable amount of time with humans on the ground, thereby portraying a terrestrial tendency. Postural Origin Theory states that terrestrial animals tend to use their right hand and arboreal their left. Therefore, here the presence of group-level left-hand biasness in the adult langurs of Dakshineswar creates a dilemma in the Postural Origin Theory.

animal behavior and cognition↗
bioRxiv2023

Identification of potential selective autophagy receptors from protein-content profiling of autophagosomes

Selective autophagy receptors (SARs) are central to cellular homeostatic and organellar recycling pathways. Over the last two decades, more than 30 SARs have been discovered and validated using a variety of experimental approaches ranging from cell biology to biochemistry, including high-throughput imaging and screening methods. Yet, the extent of selective autophagy pathways operating under various cellular contexts e.g., under basal and starvation conditions, remains unresolved. Currently, our knowledge of all known SARs and their associated cargo components is fragmentary and limited by experimental data with varying degrees of resolution. Here, we use classical predictive and modeling approaches to integrate high-quality autophagosome content profiling data with disparate datasets. We identify a global set of potential SARs and their associated cargo components active under basal autophagy, starvation-induced, and proteasome-inhibition conditions. We provide a detailed account of cellular components, biochemical pathways, and molecular processes that are degraded via autophagy. Our analysis yields a catalog of new potential SARs that satisfy the characteristics of bonafide, well-characterized SARs. We categorize them by the subcellular compartments they emerge from and classify them based on their likely mode of action. Our structural modeling validates a large subset of predicted interactions with the human ATG8 family of proteins and shows characteristic, conserved LC3-interacting region (LIR)-LIR-docking site (LDS) and Ubiquitin-interacting motif (UIM)-UIM-docking site (UDS) binding modes. Our analysis also revealed the most abundant cargo molecules targeted by these new SARs. Our findings expand the repertoire of SARs and provide unprecedented details into the global autophagic state of HeLa cells. Taken together, our findings provide motivation for the design of new experiments, testing the role of these novel factors in selective autophagy.

cell biology↗
bioRxiv2023

Composition of nasopharyngeal microbiota in individuals with SARS-COV-2 infection across three COVID-19 waves in India

Multiple variants of the SARS-CoV-2 virus have been plaguing the world through successive waves of infection over the past three years. Studies by independent research groups across geographies have shown that the microbiome composition in COVID-19 patients (CP) differ from that of healthy individuals (CN). However, such observations were based on limited-sized sample-sets collected primarily from the early days of the pandemic. Here, we study the nasopharyngeal microbiota in COVID-19 patients, wherein the samples have been collected across the three COVID-19 waves witnessed in India, which were driven by different variants of concern. We also present the variations in microbiota of symptomatic vs asymptomatic COVID-19 patients. The nasopharyngeal swabs were collected from 589 subjects providing samples for diagnostics purposes at Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India. CP showed a marked shift in the microbial diversity and composition compared to CN, in a wave-dependent manner. Rickettsiaceae was the only family that was noted to be consistently depleted in CP samples across the waves. The genera Staphylococcus, Anhydrobacter, Thermus, and Aerococcus were observed to be highly abundant in the symptomatic CP patients when compared to the asymptomatic group. In general, we observed a decrease in the burden of opportunistic pathogens in the host microbiota during the later waves of infection. To our knowledge, this is the first longitudinal study which was designed to understand the relation between the evolving nature of the virus and the changes in the human nasopharyngeal microbiota. Such studies not only pave way for better understanding of the disease pathophysiology but also help gather preliminary evidence on whether interventions to the host microbiota can help in better protection or faster recovery.

microbiology↗
bioRxiv2022

Biomechanical influence of plate configurations on mandible subcondylar fracture fixation: a finite element study

Mandible subcondylar fractures have very high complication rate, yet there is no consensus in a suitable plate design for optimal patient outcomes. The present study is aimed at understanding the subcondylar fracture fixation by comparing load transfer in intact and reconstructed fractured mandibles with five different plates: single mini, trapezoid, lambda, strut, and double-mini plates under the complete mastication cycle. Under contralateral molar occlusion (LMOL), the single mini plate resulted in the highest strains. On the contrary, during ipsilateral molar clenching (RMOL), the tensile and compressive strain distributions were found to be reversed, with the tensile strains at the posterior border resulting in lesser strain in reconstructed mandible with single mini plate. Owing to the reduced strains in the reconstructed mandibles, the contralateral molar clenching task is preferred during the immediate post-surgery period for patients. Under this contralateral molar clenching, the peak von Mises stresses in the plate decreased with increase in the number of screws. Furthermore, the presence of two arms seems beneficial to neutralise the tensile and compressive strains across load cases. Consequently, double mini and trapezoid plates were found to perform better as compared to single mini plate during the entire mastication cycle for subcondylar fracture fixation.

bioengineering↗
bioRxiv2022

Loss of heterozygosity spectrum varies with ploidy levels in natural yeast populations

The appearance of genomic variations such as loss of heterozygosity (LOH) has a significant impact on phenotypic diversity observed in a population. Recent large-scale yeast population genomic surveys have shown a high frequency of these events in natural isolates and more particularly in polyploids. However, the frequency, extent, and spectrum of LOH in polyploid organisms have never been explored and is poorly characterized to date. Here, we accumulated 5,163 LOH events over 1,875 generations in 76 mutation accumulation (MA) lines comprising nine natural heterozygous diploid, triploid, and tetraploid natural S. cerevisiae isolates from different ecological and geographical origins. We found that the rate and spectrum of LOH are variable across ploidy levels. Of the total accumulated LOH events, 8.5%, 21%, and 70.5% of them were found in diploid, triploid, and tetraploid MA lines, respectively. Our results clearly shows that the frequency of generated LOH events increases with ploidy level. In fact, the cumulative LOH rates were estimated to be 9.3 x 10-3, 2.2 x 10-2, and 8.4 x 10-2 events per division for diploids, triploids, and tetraploids, respectively. In addition, a clear bias towards the accumulation of interstitial and short LOH tracts is observed in triploids and tetraploids compared to diploids. The variation of the frequency and spectrum of LOH events across ploidy level could be related to the genomic instability, characterizing higher ploidy isolates. Highlights- Yeast isolates with a high ploidy level (e.g., 3n and 4n) accumulate a larger number of LOH events compared to diploids. - The type of events and the LOH spectrum are both variable according to the ploidy levels. - A clear bias towards the accumulation of short LOH tracts is observed in polyploids compared to diploids. - The variation in LOH spectrum is most likely related to genomic instability present in higher ploidy strains.

genomics↗
bioRxiv2022

Combined reference-free and multi-reference approaches uncover cryptic variation underlying rapid adaptation in microbial pathogens

BackgroundMicrobial species often harbor substantial functional diversity driven by structural genetic variation. Rapid adaptation from such standing variation in pathogens threatens global food security and human health. Genome wide association studies (GWAS) provide a powerful approach to identify genetic variants underlying recent pathogen evolution. However, the reliance on single reference genomes and single nucleotide polymorphisms (SNPs) obscures the true extent of adaptive genetic variation. Here, we show quantitatively how a combination of multiple reference genomes and reference-free approaches captures substantially more relevant genetic variation compared to single reference mapping. ResultsWe performed reference-genome based association mapping across 19 reference-quality genomes covering the diversity of the species. We contrasted the results with a reference-free (i.e., K-mer) approach using raw whole genome sequencing data. We assessed the relative power of these GWAS approaches in a panel of 145 strains collected across the global distribution range of the fungal wheat pathogen Zymoseptoria tritici. We mapped the genetic architecture of 49 life history traits including virulence, reproduction and growth in multiple stressful environments. The inclusion of additional reference genome SNP datasets provides a nearly linear increase in additional loci mapped through GWAS. Variants detected through the K-mer approach explained a higher proportion of phenotypic variation than a reference genome based approach, illustrating the benefits of including genetic variants beyond SNPs. ConclusionsOur study demonstrates how the power of GWAS in microbial species can be significantly enhanced by comprehensively capturing functional genetic variation. Our approach is generalizable to a large number of microbial species and will uncover novel mechanisms driving rapid adaptation in microbial populations.

genomics↗