Biology subjects

Sharma, V.

Publications and source records attributed to Sharma, V..

At least 73 records · Page 4Linked to original sources

bioRxiv2024

Exploring Probiotic Potential: A Comparative Genomics and In Silico Assessment of Genes within the Genus Geobacillus

The pursuit of new probiotic targets has seen a surge, aided by next-generation sequencing, facilitating a thorough exploration of bacterial traits. The genus Geobacillus stands out as a promising target for uncovering its potential as a probiotic. The study explored the genetic attributes of the genus Geobacillus for their resilience to gastrointestinal conditions, nutrient production, and immunomodulatory compound creation, revealing potential probiotic traits. Additionally, the research undertook predictive analyses of genomic elements such as prophages, CRISPR-Cas systems, insertion sequences, genomic islands, antibiotic resistance genes, and CAZymes. These evaluations aimed to assess the safety aspects associated with the genus Geobacillus. A comparative genomic analysis was also carried out using 18 validly published genomes of the genus Geobacillus and a few other genomes of Lactobacillus and Bifidobacterium were taken as control. Genes associated with probiotic traits like adhesion, stress tolerance (acid/bile, osmotic, oxidative), immune modulation, and molecular chaperones were uniformly detected in the Geobacillus genus. Notably, mobile genetic elements such as plasmids, prophages, and insertion sequences were absent, as were virulence factors, toxins, and Antibiotic resistance genes. Additionally, CRISPR-Cas systems and CAZymes were present. The pan-genome encompassed 25,284 protein-coding genes with translation. Comparative genomic analysis revealed an open pan-genome for Geobacillus. Pan-genome exhibited variability, particularly in genes linked to environmental interaction and secondary metabolite synthesis. In conclusion, Geobacillus appears potentially safe and well-suited for the gut habitat. However, further in vitro studies are essential to add to the knowledge of the probiotic potential of Geobacillus species. ImportanceThis comprehensive study highlights the significant probiotic potential and genetic makeup of the Geobacillus genus, shedding light on its unique attributes in adapting to extreme environmental conditions. Understanding the probiotic properties of Geobacillus is crucial amidst growing concerns over antibiotic resistance, offering promising alternatives for combating pathogenic microbes. Additionally, exploring the genetic diversity and adaptive mechanisms of Geobacillus through genomic and metagenomic approaches provides valuable insights into its biotechnological applications and evolutionary history. By employing in-silico methods and comparative analyses with established probiotic genera, this study contributes to elucidating the probiotic characteristics of Geobacillus, paving the way for further research in harnessing its beneficial traits for various applications in health, biotechnology, and environmental remediation.

microbiology↗

bioRxiv2024

A framework for quality control in quantitative proteomics

A thorough evaluation of the quality, reproducibility, and variability of bottom-up proteomics data is necessary at every stage of a workflow from planning to analysis. We share vignettes applying adaptable quality control (QC) measures to assess sample preparation, system function, and quantitative analysis. System suitability samples are repeatedly measured longitudinally with targeted methods, and we share examples where they are used on three instrument platforms to identify severe system failures and track function over months to years. Internal QCs incorporated at protein and peptide-level allow our team to assess sample preparation issues and to differentiate system failures from sample-specific issues. External QC samples prepared alongside our experimental samples are used to verify the consistency and quantitative potential of our results during batch correction and normalization before assessing biological phenotypes. We combine these controls with rapid analysis (Skyline), longitudinal QC metrics (AutoQC), and server-based data deposition (PanoramaWeb). We propose that this integrated approach to QC is a useful starting point for groups to facilitate rapid quality control assessment to ensure that valuable instrument time is used to collect the best quality data possible. Data are available on Panorama Public and on ProteomeXchange under the identifier PXD051318.

biochemistry↗

bioRxiv2024

Structural basis of respiratory complexes adaptation to cold temperatures

In response to cold, mammals activate brown fat for respiratory-dependent thermogenesis reliant on the electron transport chain (1, 2). Yet, the structural basis of respiratory complex adaptation to cold remains elusive. Herein we combined thermoregulatory physiology and cryo-EM to study endogenous respiratory supercomplexes exposed to different temperatures. A cold-induced conformation of CI:III2 (termed type 2) was identified with a [~]25{degrees} rotation of CIII2 around its inter-dimer axis, shortening inter-complex Q exchange space, and exhibiting different catalytic states which favor electron transfer. Large-scale supercomplex simulations in lipid membrane reveal how unique lipid-protein arrangements stabilize type 2 complexes to enhance catalytic activity. Together, our cryo-EM studies, multiscale simulations and biochemical analyses unveil the mechanisms and dynamics of respiratory adaptation at the structural and energetic level.

cell biology↗

bioRxiv2023

The SET1 protein of Leishmania donovani moderates the parasite's response to a hostile oxidative environment

SET domain proteins mediate their effects through the methylation of specific lysine residues on target substrates, resulting in either the stimulation or repression of downstream processes. Initially identified as histone lysine methyltransferases, they are now known to target a wide-ranging conglomeration of non-histone subtrates as well. Twenty-nine SET domain proteins have been identified in Leishmania donovani through genome sequence annotations. This study initiates the first investigation into these proteins. We find LdSET1 is predominantly cytosolic and constitutively expressed. The set1 gene is not essential, although its deletion slows promastigote growth and hypersensitizes the parasite to hydroxyurea-induced G1/S arrest. Intriguingly, set1-nulls proliferate more proficiently than set1+/+ parasites within host macrophages, suggesting that LdSET1 moderates the parasites response to the inhospitable intracellular oxidative environment. set1-null parasites are highly tolerant to H2O2-induced oxidative stress in in vitro promastigote cultures as well, reflected in their growth pattern as well as almost complete absence of DNA damage at the H2O2 concentrations tested. This is linked to ROS levels remaining virtually unperturbed in response to H2O2 treatment in set1-nulls, contrasting to increased ROS in set1+/+ cells under similar conditions. In analyzing the cells ability to scavenge hydroperoxides we find that peroxidase activity is not upregulated in response to H2O2 exposure in set1-nulls. Rather, the constitutive basal levels of peroxidase activity are significantly higher in these cells, implicating this to be a factor contributing to the parasites apparent resistance to H2O2. The higher levels of peroxidase activity in set1-nulls are coupled to upregulation of tryparedoxin peroxidase transcripts in these cells. Thus, LdSET1 tunes the parasites behavior within host cells, enabling establishment and persistence of infection, and maintaining the balance with host without eradicating the host cell population it needs for survival. These findings uncover a new dimension to the mechanisms controlling the interplay of Leishmania-host interactions. Author SummaryLeishmaniases are a group of diseases afflicting people across 88 countries. Manifested in three forms: cutaneous, subcutaneous and visceral, different species cause the different forms of the disease. Leishmania donovani is one of the species causing Visceral Leishmaniasis, and its cellular processes are an area of intensive investigations. These protozoan parasites display an unusual pattern of transcription, and gene regulation occurs primarily through epigenetic mechanisms and post-transcriptional processes. SET proteins control gene expression by methylating histones as well as non-histone proteins. In this study we have examined the role of the LdSET1 protein. We find that while the set1 gene is not essential to cell survival, deletion of the set1 gene makes the parasite highly tolerant to the effects of an oxidizing environment, signifying that the LdSET1 protein plays a role in regulating the cells response to oxidative stress. LdSET1 appears to moderate the parasites survival in the oxidative intracellular milieu of host macrophages, controlling it such that infection is firmly established, and persistent, without wiping out the population of host cells it needs for survival.

cell biology↗

bioRxiv2023

In Vivo Antiviral Efficacy of LCTG-002, a Pooled, Purified Human Milk Secretory IgA product, Against SARS-CoV-2 in a Murine Model of COVID-19

Immunoglobulin A (IgA) is the most abundant antibody (Ab) in human mucosal compartments including the respiratory tract, with the secretory form of IgA (sIgA) being dominant and uniquely stable in these environments. sIgA is naturally found in human milk, which could be considered a global resource for this biologic, justifying the development of human milk sIgA as a dedicated airway therapeutic for respiratory infections such as SARS-CoV-2. In the present study, methods were therefore developed to efficiently extract human milk sIgA from donors who were either immunologically naive to SARS-CoV-2 (pooled as a control IgA) or had recovered from a PCR-confirmed SARS-CoV-2 infection that elicited high-titer anti-SARS-CoV-2 Spike sIgA Abs in their milk (pooled together to make LCTG-002). Mass spectrometry determined that proteins with a relative abundance of 1.0% or greater were all associated with sIgA. None of the proteins exhibited statistically significant differences between batches. Western blot demonstrated all batches consisted predominantly of sIgA. Compared to control IgA, LCTG-002 demonstrated significantly higher binding to Spike, and was also capable of blocking the Spike - ACE2 interaction in vitro with 6.3x greater potency compared to control IgA (58% inhibition at [~]240ug/mL). LCTG-002 was then tested in vivo for its capacity to reduce viral burden in the lungs of K18+hACE2 transgenic mice inoculated with SARS-CoV-2. LCTG-002 was demonstrated to significantly reduce SARS-CoV-2 titers in the lungs compared to control IgA when administered at either 250ug/day or 1 mg/day, as measured by TCID50, plaque forming units (PFU), and qRT-PCR, with a maximum reduction of 4.9 logs. This innovative study demonstrates that LCTG-002 is highly pure, efficacious, and well tolerated in vivo, supporting further development of milk-derived, polyclonal sIgA therapeutics against SARS-CoV-2 and other mucosal infections.

immunology↗

bioRxiv2023

Long-term history dependence of growth rates of E. coli after nutrient shifts

According to a widely accepted paradigm of microbiology, steady-state growth rates are determined solely by current growth conditions1-3 and adaptations between growth states are rapid, as recently recapitulated by simple resource allocation models4. However, even in microbes overlapping regulatory networks can yield multi-stability or long-term cellular memory. Species like Listeria monocytogenes5 and Bacillus subtilis "distinguish" distinct histories for the commitment to sporulation6, but it is unclear if these states can persist over many generations. Remarkably, studying carbon co-utilization of Escherichia coli, we found that growth rates on combinations of carbon sources can depend critically on the previous growth condition. Growing in identical conditions, we observed differences in growth rates of up to 25% and we did not observe convergence of growth rates over 15 generations. We observed this phenomenon occurs across combinations of different phosphotransferase (PTS) substrates with various gluconeogenic carbon sources and found it to depend on the transcription factor Mlc.

microbiology↗

bioRxiv2023

Role of protonation states in stability of molecular dynamics simulations of high-resolution membrane protein structures

Classical molecular dynamics (MD) simulations provide unmatched spatial and time resolution of protein structure and function. However, accuracy of MD simulations often depends on the quality of force field parameters and the time scale of sampling. Another limitation of conventional MD simulations is that the protonation states of titratable amino acid residues remain fixed during simulations, even though protonation state changes coupled to conformational dynamics are central to protein function. Due to the uncertainty in selecting protonation states, classical MD simulations are sometimes performed with all amino acids modeled in their standard charged states at pH 7. Here we performed and analyzed classical MD simulations on high-resolution cryo-EM structures of two membrane proteins that transfer protons by catalyzing protonation/deprotonation reactions. In simulations performed with amino acids modeled in their standard protonation state the structure diverges far from its starting conformation. In comparison, MD simulations performed with pre-determined protonation states of amino acid residues reproduce the structural conformation, protein hydration, and protein-water and protein-protein interactions of the structure much better. The results suggest it is crucial to perform basic protonation state calculations, especially on structures where protonation changes play an important functional role, prior to launching any MD simulations. Furthermore, the combined approach of protonation state prediction and MD simulations can provide valuable information on the charge states of amino acids in the cryo-EM sample. Even though accurate prediction of protonation states currently remains a challenge, we introduce an approach of combining pKa prediction with cryo-EM density map analysis that helps in improving not only the protonation state predictions, but also the atomic modeling of density data.

biophysics↗

bioRxiv2023

Reprogramming of breast tumor-associated macrophages with modulation of arginine metabolism

HER2+ breast tumors have abundant immune-suppressive cells, including M2-type tumor associated macrophages (TAMs). While TAMs consist of the immune-stimulatory M1-type and immune-suppressive M2-type, M1/M2-TAM ratio is reduced in immune-suppressive tumors, contributing to their immunotherapy refractoriness. M1 vs. M2-TAM formation depends on differential arginine metabolism, where M1-TAMs convert arginine to nitric oxide (NO) and M2- TAMs convert arginine to polyamines (PAs). We hypothesize that such distinct arginine metabolism in M1- vs M2-TAMs is attributed to different availability of BH4 (NO synthase cofactor) and that its replenishment would reprogram M2-TAMs to M1-TAMs. Recently, we reported that sepiapterin (SEP), the endogenous BH4 precursor, elevates the expression of M1- TAM markers within HER2+ tumors. Here, we show that SEP restores BH4 levels in M2-TAMs, which then redirects arginine metabolism to NO synthesis and converts M2-TAMs to M1-TAMs. The reprogrammed TAMs exhibit full-fledged capabilities of antigen presentation and induction of effector T cells to trigger immunogenic cell death of HER2+ cancer cells. This study substantiates the utility of SEP in metabolic shift of HER2+ breast tumor microenvironment as a novel immunotherapeutic strategy.

cancer biology↗

bioRxiv2023

A sucrose non-fermenting-1-related protein kinase 1 gene from wheat, TaSnRK1α regulates starch biosynthesis by modulating AGPase activity

Major portion of wheat grain consist of carbohydrate, mainly starch. The proportion of amylose and amylopectin in starch greatly influence the end product quality. Advancement in understanding starch biosynthesis pathway and modulating key genes has enabled the genetic modification of crops resulting in enhanced starch quality. However, the regulation of starch biosynthesis genes still remains unexplored. So, to expand the limited knowledge, here, we characterized a Ser/Thr kinase, SnRK1 in wheat and determined its role in regulating starch biosynthesis. SnRK1 is an evolutionary conserved protein kinase and share homology to yeast SNF1. Yeast complementation assay suggest TaSnRK1 restore growth defect and promotes glycogen accumulation. Domain analysis and complementation assay with truncated proteins suggest the importance of ATP-binding and UBA domain in TaSnRK1 activity. Sub-cellular localization identified nuclear and cytoplasmic localization of TaSnRK1 in tobacco leaves. Further, heterologous over-expression (O/E) of TaSnRK1 in Arabidopsis not only led to increase in starch content but also enlarges the starch granules. TaSnRK1 was found to restore starch accumulation in Arabidopsis kin10. Remarkably, TaSnRK1 O/E increase the AGPase activity suggesting the direct regulation of rate limiting enzyme AGPase involved in starch biosynthesis. Furthermore, in vitro and in vivo interaction assay reveal that TaSnRK1 interacts with AGPase large sub-unit. Overall, our findings indicate that TaSnRK1 plays role in starch biosynthesis by regulating AGPase activity. HighlightsO_LITaSnRK1 is Ser/Thr kinase in wheat and show dual localization in nucleus and cytoplasm. C_LIO_LIOverexpression of TaSnRK1 increases starch content and enlarges starch granules in Arabidopsis. C_LIO_LITaSnRK1 enhances AGPase activity thereby regulating starch biosynthesis. C_LIO_LITaSnRK1 directly interact with AGPase large subunit in vivo and in vitro. C_LI

molecular biology↗

bioRxiv2023

E3 ubiquitin ligase Deltex facilitates the expansion of Wingless gradient and antagonizes Wingless signaling through a conserved mechanism of transcriptional effector Armadillo/β-catenin degradation

The Wnt/Wg pathway controls myriads of biological phenomena throughout the development and adult life of all organisms across the phyla. Thus, an aberrant Wnt signaling is associated with a wide range of pathologies in humans. Tight regulation of Wnt/Wg signaling is required to maintain proper cellular homeostasis. Here we report a novel role of E3 ubiquitin ligase Deltex in Wg signaling regulation. Drosophila dx genetically interacts with wg and its pathway components. Further, Dx LOF results in a reduced spreading of Wg while its over-expression expands the diffusion gradient of the morphogen. We attribute this change in Wg gradient to the endocytosis of Wg through Dx which directly affects the short and long-range Wg targets. We also demonstrate the role of Dx in regulating Wg effector Armadillo where Dx down-regulates Arm through proteasomal degradation. We also showed the conservation of Dx function in the mammalian system where DTX1 is shown to bind with {beta}-catenin and facilitates its proteolytic degradation, spotlighting a novel step that potentially modulates Wnt/Wg signaling cascade.

developmental biology↗

bioRxiv2023

Excitatory neuron-specific suppression of the integrated stress response pathway contributes to autism-related phenotypes in a mouse model of fragile X syndrome

Dysregulation of protein synthesis is one of the key mechanisms underlying autism spectrum disorder (ASD). However, the role of a major pathway controlling protein synthesis, the integrated stress response (ISR), in ASD remains poorly understood. Here, we demonstrate that the main arm of the ISR, eIF2 phosphorylation (p-eIF2), is suppressed in excitatory but not inhibitory neurons in a mouse model of fragile X syndrome (FXS; Fmr1-/y). We further show that the decrease in p-eIF2 is mediated via activation of the mTORC1. Genetic reduction of p-eIF2 only in excitatory neurons is sufficient to increase general protein synthesis and cause autism-like behavior. In Fmr1-/y mice, genetic restoration of p-eIF2 solely in excitatory neurons reverses elevated protein synthesis and rescues autism-related phenotypes. Thus, we reveal a previously unknown causal relationship between excitatory neuron-specific translational control via the ISR pathway, general protein synthesis and core phenotypes reminiscent of autism in a mouse model of FXS.

neuroscience↗

bioRxiv2023

Downregulation of ribosomal RNA (rRNA) genes in human head and neck squamous cell carcinoma (HNSCC) cells is linked to rDNA promoter hypermethylation

Eukaryotes carry hundreds of ribosomal RNA (rRNA) genes as tandem arrays, which generate rRNA for protein synthesis. Humans carry ~ 400 rRNA gene copies, which are epigenetically regulated. Dysregulation of rRNA synthesis and ribosome biogenesis are characteristic features of cancers. Targeting aberrant rRNA expression for cancer therapy is being explored. Head and neck squamous cell carcinoma (HNSCC) is among the most prevalent cancers globally. Using quantitative PCR and bisulfite sequencing, we show that rRNA genes are downregulated and their promoters are hypermethylated in HNSCC cell lines. These finding may have relevance for prognosis and diagnosis for HNSCC.

cancer biology↗

bioRxiv2022

SARS-CoV-2 causes periodontal fibrosis by deregulating mitochondrial beta-oxidation

The global high prevalence of COVID-19 is a major challenge for health professionals and patients. SARS-CoV-2 virus mutate predominantly in the spike proteins, whilst the other key viral components remain stable. Previous studies have shown that the human oral cavity can potentially act as reservoir of the SARS-CoV-2 virus. COVID-19 can cause severe oral mucosa lesions and is likely to be connected with poor periodontal conditions. However, the consequence of SARS-CoV-2 viral infection on human oral health has not been systematically examined. In this research, we aimed to study the pathogenicity of SARS-CoV-2 viral components on human periodontal tissues and cells. We found that by exposing to SARS-CoV-2, especially to the viral envelope and membrane proteins, the human periodontal fibroblasts could develop fibrotic pathogenic phenotypes, including hyperproliferation that was concomitant induced together with increased apoptosis and senescence. The fibrotic degeneration was mediated by a down-regulation of mitochondrial {beta}-oxidation in the fibroblasts. Fatty acid {beta}-oxidation inhibitor, etomoxir treatment could mirror the same pathological consequence on the cells, similar to SARS- CoV-2 infection. Our results therefore provide novel mechanistic insights into how SARS- CoV-2 infection can affect human periodontal health at the cell and molecular level with potential new therapeutic targets for COVID-19 induced fibrosis.

molecular biology↗

bioRxiv2022

Temporal Vascular Endothelial Growth Factor Sub-type gene Switching in SARS-CoV Pathogenesis. Interpretation through in vivo Murine C57BL Models

This study examines temporal gene expression (GE) patterns in a murine model of SARS-CoV infection. We focused on a Temporal Gene Set (TGS) comprising pro-inflammatory genes (TNF, NFKB1, VEGF-A) and VEGF-B. A systematic search of the NCBI Geo database for MA15 (SARS-CoV) pulmonary studies using C57BL Wild (WT) mice and filtering according to TGS GE patterns eluded seven datasets for further analysis. Encompassing the GE profiles from these datasets alluded to a rising and falling pattern in TNF and NFKB1 GE. Also, our findings reveal a temporal decrease in VEGF-A GE coinciding with an increase in VEGF-B GE post-immunogenic stimulation. Notably, differential responses were observed with the MA15 dosage and in comparison, to other antigens (dORF6 and NSP16). Further, the human SARS-CoV-2 gene enrichment in this murine study confirms the MA15 murine models relevance for SARS research. Our study also suggests potential interactions between SARS-CoV-2 Spike protein and VEGF-related receptors, hinting at other pathophysiological mechanisms. Our results indicate severe inflammation may lead to a flattened VEGF-B GE response, influencing VEGF-Bs cell survival role. We underline the significance of considering VEGF-A/B interactions, particularly temporal differences, in manipulating angiogenic processes. Future research needs to consider temporal changes in VEGF-A and VEGF-B GE, in terms of time-associated gene-switching, in line with changing host inflammation.

immunology↗

bioRxiv2022

Benchmarking solutions to the T-cell receptor epitope prediction problem: IMMREP22 workshop report

Many different solutions to predicting the cognate epitope target of a T-cell receptor (TCR) have been proposed. However several questions on the advantages and disadvantages of these different approaches remain unresolved, as most methods have only been evaluated within the context of their initial publications and data sets. Here, we report the findings of the first public TCR-epitope prediction benchmark performed on 23 prediction models in the context of the ImmRep 2022 TCR-epitope specificity workshop. This benchmark revealed that the use of paired-chain alpha-beta, as well as CDR1/2 or V/J information, when available, improves classification obtained with CDR3 data, independent of the underlying approach. In addition, we found that straight-forward distance-based approaches can achieve a respectable performance when compared to more complex machine-learning models. Finally, we highlight the need for a truly independent follow-up benchmark and provide recommendations for the design of such a next benchmark.

bioinformatics↗

bioRxiv2022

Exploring Capacitance and Non-Linear Electrokinetics in Nanopores Yields Insight into Single Molecule Recordings

The pervasive model for a solvated, ion-filled nanopore is often a resistor in parallel with a capacitor. However, for conical nanopore geometries, we propose the inclusion of a Warburg-like element which is necessary to explain otherwise anomalous observations such as negative capacitance and lowpass filtering of translocation events (i.e., a phenomenon we term Warburg filtering). The negative capacitance observed here is characterized as having long equilibration times and memory (i.e., mem-capacitance) at negative voltages. Next, we used the transient occlusion of the pore using {lambda}-DNA and 10-kbp DNA to test whether events are being attenuated by purely ionic phenomena even when there is sufficient amplifier bandwidth. The inclusion of the Warburg-like element is mechanistically linked to concentration polarization and the activation energy to generate and maintain localized concentration gradients. We conclude the study with a new interpretation of molecular translocations which is not simply based on the pulse-like resistance changes but rather a complex and non-linear storage of ions that changes during molecular transit.

biophysics↗

bioRxiv2022

Nanobody engineering for SARS-CoV-2 neutralization and detection

In response to the ongoing SARS-CoV-2 pandemic, the quest for coronavirus inhibitors has inspired research on a variety of small proteins beyond conventional antibodies, including robust single-domain antibody fragments, nanobodies. Here, we explore the potential of nanobody engineering in the development of antivirals and diagnostic tools. Through fusion of nanobody domains that target distinct binding sites, we engineered multimodular nanobody constructs that neutralize wild-type SARS-CoV-2 and the Alpha and Delta variants with high potency, with IC50 values up to 50 pM. However, we observed a limitation in the efficacy of multimodular nanobodies against the Beta (B.1.351) and Omicron variants (B.1.1.529), underlining the importance of accounting for viral evolution in the design of biologics. To further explore the applications of nanobody engineering in outbreak management, we present a novel detection assay, based on fusions of nanobodies with fragments of NanoLuc luciferase that can detect sub-nanomolar quantities of the SARS-CoV-2 spike protein in a single step. Our work showcases the potential of nanobody engineering to combat emerging infectious disease.

microbiology↗

bioRxiv2022

Integrating gene annotation with orthology inference at scale

Annotating coding genes and inferring orthologs are two classical challenges in genomics and evolutionary biology that have traditionally been approached separately, limiting scalability. We present TOGA, a method that integrates structural gene annotation and orthology inference. TOGA implements a different paradigm to infer orthologous loci, improves ortholog detection and annotation of conserved genes compared to state-of-the-art methods, and handles even highly-fragmented assemblies. TOGA scales to hundreds of genomes, which we demonstrate by applying it to 488 placental mammal and 501 bird assemblies, creating the largest comparative gene resources so far. Additionally, TOGA detects gene losses, enables selection screens, and automatically provides a superior measure of mammalian genome quality. Together, TOGA is a powerful and scalable method to annotate and compare genes in the genomic era.

genomics↗