Biology subjects

Tang, H.

Publications and source records attributed to Tang, H..

At least 73 records · Page 4Linked to original sources

bioRxiv2024

Leveraging the Human Panproteome to Enhance Peptide and Protein Identification in Proteomics and Metaproteomics

In this paper, we developed a novel approach to utilize the human pangenome to improve peptide and protein identification from proteomic data (MS/MS spectra). We propose a new data structure called panproteome graph (PPG), in which nodes are tryptic peptides, to represent the human pangenome. The PPG can be built in linear time and can be utilized via graph traversal using a depth-first search algorithm to generate potential peptides for peptide identification in proteomics. The PPG built using the 47 human proteomes from the Human Pangenome Reference Consortium (HPRC) coupled with UniProt human proteins resulted in more than 4.2M tryptic peptides, a 26% increase as compared to when only the UniProt proteins were included. Graph-based analysis of the PPG revealed a giant disconnected component with about 3M nodes, suggesting substantial sharing of tryptic peptides among proteins. We applied tryptic peptides derived from PPG to characterize three collections of human proteomic and metaproteomic datasets, and our results showed that by exploiting the human pangenome, we were able to increase the number of identified peptides on all datasets we tested (about 8% increase across all three collections). We also showed that using more complete human proteome would be useful for reducing potential misidentification of human peptides as microbial peptides, a problem that was previously studied but based on genomic sequencing data. Our tool for building PPG is available in a GitHub repo PPGpep, and PPG-derived tryptic peptides can be utilized by MetaProD, a pipeline for both human and bacterial peptide and protein identification from (meta)proteomics datasets.

bioinformatics↗

bioRxiv2024

TopLib: Building and searching top-down mass spectral libraries for proteoform identification

Mass spectral library search is a widely used approach for spectral identification in mass spectrometry (MS)-based proteomics. While numerous methods exist for building and searching bottom-up mass spectral libraries, there is a lack of software tools for top-down mass spectral libraries. To fill the gap, we introduce TopLib, the first software package designed for building and searching top-down spectral libraries. TopLib utilizes an efficient spectral representation technique to reduce database size and improve query speed and performance. We systematically evaluated various spectral representation techniques and scoring functions for top-down spectral clustering and search. Our results demonstrated that TopLib is 140 times faster and achieves better reproducibility in proteoform identification compared with conventional database search methods in top-down MS.

bioinformatics↗

bioRxiv2024

PAM-flexible adenine base editing rescues hearing loss in a humanized MPZL2 mouse model harboring an East Asian founder mutation

Hearing loss is one of the most prevalent sensory disorders, but no commercial biological treatments are currently available. Here, we identified an East Asia-specific founder mutation, the homozygous c.220C>T mutation in MPZL2, that contributes to a significant proportion of hereditary deafness cases in our cohort study. We found that the disease-causing mutation could be targetable by adenine base editors (ABEs) that enable A{middle dot}T-to-G{middle dot}C base corrections without DNA double-strand breaks. To demonstrate this, we developed a humanized mouse model (hMPZL2Q74X/Q74X) that recapitulates human MPZL2 deafness and leads to progressive hearing loss. A PAM-flexible ABE variant with reduced bystander and off-target effects (ABE8eWQ-SpRY:sgRNA3) was packaged in dual adeno-associated viruses (AAVs) and injected into the inner ear of hMPZL2Q74X/Q74X mice and effectively corrected the mutation. This treatment significantly restored hearing function, improved inner ear structural integrity, and reversed altered gene expression. Base editing may hold therapeutic potential for hereditary deafness, including most cases of MPZL2 deafness.

genetics↗

bioRxiv2024

Leveraging large language models for metabolic engineering design

Establishing efficient cell factories involves a continuous process of trial and error due to the intricate nature of metabolism. This complexity makes predicting effective engineering targets a challenging task. Therefore, it is vital to learn from the accumulated successes of previous designs for advancing future cell factory development. In this study, we developed a method based on large language models (LLMs) to extract metabolic engineering strategies from research articles on a large scale. We created a database containing over 29006 metabolic engineering entries, 1210 products and 751 organisms. Using this extracted data, we trained a hybrid model combining deep learning and mechanistic approaches to predict engineering targets. Our model outperformed traditional metabolic engineering target prediction algorithms, excelled in predicting the effects of gene modifications, and generalized well to out-of-distribution products and multiple gene combinations. Our study provides a valuable dataset, a chatbot, and an engineering target prediction model for the metabolic engineering field and exemplifies an efficient method for leveraging existing knowledge for future predictions.

systems biology↗

bioRxiv2024

Characterization the gene editing with miniature nucleases TnpB, IscB and enIscB in Escherichia coli strains

DNA nucleases TnpB and IscB were regarded as new antibacterial strategy to combat the drug-resistant bacteria represented by Escherichia coli due to its specificity in targeting DNA and smallest size, but the genome-editing of TnpB/IscB in E. coli remains unclear. This study characterized the genome-editing of TnpB/IscB in E. coli strains. First, the toxicity and cleavage results showed TnpB only worked in E. coli MG1655, while IscB and enIscB could perform in ATCC9637 and BL21(DE3). Next, TnpB-based genome-editing tool was established in MG1655, while IscB/enIscB achieved in ATCC9637/BL21(DE3). The copy number of TnpB/IscB/enIscB were changed to explore the impact of editing efficiency. Moreover, the editing plasmids were successfully cured. Finally, the escaping mechanism of E. coli under editing of TnpB/IscB was revealed. Overall, this study successfully applied TnpB/IscB/enIscB to genome-editing in E. coli, which will broaden genetic manipulation toolbox in E. coli and facilitate the development of new antimicrobial drugs.

microbiology↗

bioRxiv2024

An Automated High-throughput Affinity Capture-Mass Spectrometry Platform with Data-Independent Acquisition

Affinity capture (AC) combined with mass spectrometry (MS)-based proteomics is highly utilized throughout the drug discovery pipeline to determine small molecule target selectivity and engagement. However, the tedious sample preparation steps and time-consuming MS acquisition process has limited its use in high-throughput format. Here, we report an automated workflow employing biotinylated probes and streptavidin magnetic beads for small molecule target enrichment in 96-well plate format, ending with direct sampling from EvoSep Solid Phase Extraction tips for liquid chromatography (LC)-tandem mass spectrometry (MS/MS) analysis. The streamlined process significantly reduced both overall and hands-on time needed for sample preparation. Additionally, we developed a data-independent acquisition-mass spectrometry (DIA-MS) method to establish an efficient label-free quantitative chemical proteomic kinome profiling workflow. DIA-MS yielded coverage of [~]380 kinases, a >60% increase compared to using a data-dependent acquisition (DDA)-MS method and provided reproducible target profiling of the kinase inhibitor dasatinib. We further showcased the applicability of this AC-MS workflow for assessing the selectivity of two clinical-stage CDK9 inhibitors against [~]250 probe-enriched kinases. Our study here provides a roadmap for efficient target engagement and selectivity profiling in native cell or tissue lysates using AC-MS.

biochemistry↗

bioRxiv2024

Potent LILRB1 D1D2-containing antibodies inhibit RIFIN-mediated immune evasions

The spread of drug-resistant malaria parasites presents a major challenge to global efforts in malaria control, increasing the urgency for new treatments and vaccines. A promising approach involves developing antibodies that can counteract the parasites immune evasion mechanisms. In this study, we designed a receptor-containing antibody, targeting the D1D2 domain of the LILRB1 receptor, using a structure-based rational approach. We began with the MDB1 antibody as a scaffold and replaced the LILRB1-D3D4 insertion domain with D1D2.v, a high-affinity variant optimized through yeast surface display. The modified D1D2.v-IgG efficiently blocked the interaction between RIFIN#1 (from PF3D7_1254800) and LILRB1, thereby reversing the inhibition of NK cell activity caused by RIFIN#1. To further enhance this effect, we developed NK-biAb, a bispecific antibody based on D1D2.v-IgG that targets both RIFIN#1 and NKG2D receptors. NK-biAb exhibited superior biological performance compared to D1D2.v-IgG alone. These findings provide a clear framework for designing antibodies that target immune evasion in malaria, potentially guiding the development of more effective treatments and vaccines.

biochemistry↗

bioRxiv2024

Acupuncture triggers earlier recovery from ischemic stroke than sham needling in a rat model

Summary paragraphAcupuncture, a traditional Chinese medical treatment that has been practiced for over 2,000 years, is widely used around the world [1]. However, its efficacy and distinction from random stimulation are still being questioned [2, 3]. Over the years, many studies have reported either favorable, neutral or even skeptical outcomes regarding the treatment effect of acupuncture on diverse ailments [4-7]. The major question behind this controversy is whether acupuncture is different from random needle insertion and whether its efficacy can be attributed to the placebo effect [8, 9]. Here, we use micro-positron emission tomography (microPET) imaging in a randomized controlled animal study to show that acupuncture facilitates faster recuperation in comparison to sham acupuncture and blank control. Based on the microPET imaging of subjects undergoing daily acupuncture over two weeks duration, we dynamically monitored the metabolic activity levels in different brain regions and found that both acupoint and non-acupoint stimulation could improve ischemic stroke recovery. This finding is consistent with previous reports that both acupuncture and sham needling show a positive effect in the treatment of diseases [4, 5, 8]. More importantly, we further found that rats receiving acupuncture at Baihui (GV20) and Shuigou (GV26), two commonly used acupoints for stroke rehabilitation based on the concept of the meridian system, showed earlier recovery effects than rats receiving sham needling treatment. This difference mainly appeared in regions involved in motor control and was validated by a balance beam walking test. Our findings, in conjunction with a recent electroacupuncture study that revealed a neuroanatomical pathway to mediate the vagal-adrenal anti-inflammatory axis [10], provide quantitative evidence supporting the specificity of acupoints in acupuncture therapy.

neuroscience↗

bioRxiv2024

Rational Design of a Flavoenzyme for Aerobic Nicotine Catabolism

Enzymatic therapy with nicotine-degrading enzyme is a new strategy in treating nicotine addiction, which can reduce nicotine concentrations and weaken withdrawal in the rat model. However, when O2 is used as the electron acceptor, no satisfactory performance has been achieved with one of the most commonly studied and efficient nicotine-catabolizing enzymes, NicA2. To obtain more efficient nicotine-degrading enzyme, we rationally designed and engineered a flavoenzyme Pnao, which shares high structural similarity with NicA2 (RMSD = 1.143 [A]) and efficiently catalyze pseudooxynicotine into 3-succinoyl-semialdehyde pyridine using O2. Through amino acid alterations with NicA2, five Pnao mutants were generated, which can degrade nicotine in Tris-HCl buffer and retained catabolic activity on its natural substrate. Nicotine-1-N-oxide was identified as one of the reaction products. Four of the derivative mutants showed activity in rat serum and Trp220 and Asn224 were found critical for enzyme specificity. Our findings offer a novel avenue for research into aerobic nicotine catabolism and provides a promising method of generating additional nicotine-catalytic enzymes.

molecular biology↗

bioRxiv2024

Identification of BiP as a temperature sensor mediating temperature-induced germline sex reversal

Besides regulation by karyotype, sex determination is also modulated by environmental cues like temperature, but the involving temperature-transduction mechanism remains elusive. Moreover, while sex determination was traditionally seen as dictated exclusively by either karyotype or temperature, recent observations suggest these factors can co-regulate sex, posing a mechanistic mystery. Here, we discovered that certain wild-isolated and mutant C. elegans strains displayed genotypic-germline-sex-determination (GGSD) but with a temperature override. We found that ER chaperone BiP transduces temperature into germline-sex-governing signal and enables the co-existence of GGSD and temperature-dependent-germline-sex-determination (TGSD). Mechanistically, BiP availability is reduced at warmer temperatures through detecting increased ER-protein-folding burden, which promotes male-germline-fate through ERAD-mediated downregulation of the oocyte-fate driving factor, TRA-2. Remarkably, we can induce a switch between GGSD and TGSD by manipulating this newly-discovered process. Functionally, TGSD facilitates C. elegans hermaphrodites in maintaining brood size at warmer temperatures. Moreover, BiP also acts in germline-sex-determination in a dioecious nematode. Collectively, our findings identify thermosensitive BiP as a conserved temperature sensor in TGSD and provide mechanistic insights into the fascinating transition of GGSD and TGSD.

developmental biology↗

bioRxiv2024

Head dopaminergic and serotonergic neurons monitor alterations in gut bacterial activity through a gut-brain-gut axis

The brain is suggested to monitor gut microbial changes to critically maintain health, whereas the particular bacterial alterations and the mechanisms involved are largely unclear. Here, through a genome-wide screen, we identified 29 E. coli genes whose inactivation can be surveilled by C. elegans head dopaminergic and serotonergic neurons through increasing host neuronal dopamine and serotonin biosynthesis. Mechanistically, we found that these head neurons respond to the E. coli lack of respiratory chain genes by detecting the bacteria-caused reductions in host labile iron levels that impair intestinal mitochondria, and the intestine-expressed mitochondrial stress sensor ATFS-1 is critically involved. Furthermore, this neuronal response in turn promotes intestinal ferritin-1 expression to counteract bacteria-caused labile iron reduction and thereby maintaining mitochondrial function. Our findings systematically identify bacterial activity changes that elevate brain dopamine and serotonin levels and unveil an unexpected gut-brain-gut axis in which the head neurons inspect bacterial activity-mediated changes in host iron metabolism and mitochondrial function, enlightening crucial roles and mechanisms of brain in surveilling microbial activity alterations.

developmental biology↗

bioRxiv2024

Clonal evolution of hematopoietic stem cells after cancer chemotherapy

Normal hematopoietic stem and progenitor cells (HSPCs) inherently accumulate somatic mutations and lose clonal diversity with age, processes implicated in the development of myeloid malignancies1. The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal HSPCs is not well defined. We conducted whole-genome sequencing on 1,032 single-cell-derived HSPC colonies from 10 patients with multiple myeloma (MM), who had undergone various chemotherapy regimens. Our findings reveal that melphalan treatment distinctly increases mutational burden with a unique mutation signature, whereas other MM chemotherapies do not significantly affect the normal mutation rate of HSPCs. Among these therapy-induced mutations were several oncogenic drivers such as TET2 and PPM1D. Phylogenetic analysis showed a clonal architecture in post-treatment HSPCs characterized by extensive convergent evolution of mutations in genes such as TP53 and PPM1D. Consequently, the clonal diversity and structure of post-treatment HSPCs mirror those observed in normal elderly individuals, suggesting an accelerated clonal aging due to chemotherapy. Furthermore, analysis of matched therapy-related myeloid neoplasm (t-MN) samples, which occurred 1-8 years later, enabled us to trace the clonal origin of t-MNs to a single HSPC clone among a group of clones with competing malignant potential, indicating the critical role of secondary mutations in dictating clonal dominance and malignant transformation. Our findings suggest that cancer chemotherapy promotes an oligoclonal architecture with multiple HSPC clones possessing competing leukemic potentials, setting the stage for the selective emergence of a singular clone that evolves into t-MNs after acquiring secondary mutations. These results underscore the importance of further systematic research to elucidate the long-term hematological consequences of cancer chemotherapy.

cancer biology↗

bioRxiv2024

The Unexpected Membrane Targeting of Marchantia Short PIN Auxin Exporters Illuminates Sequence Determinants and Evolutionary Significance

The plant hormone auxin and its directional transport are crucial for growth and development. PIN auxin transporters, on account of their polarized distribution, are instrumental in guiding auxin flow across tissues. Based on protein length and subcellular localization, the PIN family is classified into two groups: plasma membrane (PM)-localized long PINs and endoplasmic reticulum (ER)-localized short PINs. The origin of PINs was traced to the alga Klebsormidium, with a single PM-localized long KfPIN. Bryophytes, the earliest land plant clade, represent the initial clade harboring the short PINs. We tracked the evolutionary trajectory of the short PINs and explored their function and localization in the model bryophyte Marchantia polymorpha, which carries four short and one long PIN. Our findings reveal that all short MpPINs can export auxin, and they are all PM-localized with MpPINX and MpPINW exhibiting asymmetric distribution. We identified a unique miniW domain within the MpPINW hydrophilic loop region, which is sufficient for its PM localization. Phosphorylation site mutations within the miniW domain abolish the PM localization. These findings not only identify the essential sequence determinant of PINs PM localization but also provide a unique insight into the evolution of ER-localized PINs. Short MpPINW, which is evolutionarily positioned between the ancestral long PINs and contemporary short PINs, still preserves the critical region essential for its PM localization. We propose that throughout land plant evolution, the unique miniW domain has been gradually lost thus converting the PM-localized short PINs in bryophytes to ER-localized short PINs in angiosperms. IMPORTANTO_LIManuscripts submitted to Review Commons are peer reviewed in a journal-agnostic way. C_LIO_LIUpon transfer of the peer reviewed preprint to a journal, the referee reports will be available in full to the handling editor. C_LIO_LIThe identity of the referees will NOT be communicated to the authors unless the reviewers choose to sign their report. C_LIO_LIThe identity of the referee will be confidentially disclosed to any affiliate journals to which the manuscript is transferred. C_LI GUIDELINESO_LIFor reviewers: https://www.reviewcommons.org/reviewers C_LIO_LIFor authors: https://www.reviewcommons.org/authors C_LI CONTACTThe Review Commons office can be contacted directly at: office@reviewcommons.org

plant biology↗

bioRxiv2024

Inactivation of a non-canonical gp130 signaling arm attenuates chronic systemic inflammation and multimorbidity induced by a high-fat diet.

Interleukin-6 (IL-6) is a major pro-inflammatory cytokine for which the levels in plasma demonstrate a robust correlation with age and body mass index (BMI) as part of the senescence-associated secretory phenotype. IL-6 cytokines also play a crucial role in metabolic homeostasis and regenerative processes, primarily via the canonical STAT3 pathway. Thus, selective modulation of IL-6 signaling may offer a unique opportunity for therapeutic interventions. Recently, we discovered that a non-canonical signaling pathway downstream of tyrosine (Y) 814 within the intracellular domain of gp130, the IL-6 co-receptor, is responsible for the recruitment and activation of SRC family of kinases (SFK). Mice with constitutive genetic inactivation of gp130 Y814 (F814 mice) show accelerated resolution of inflammatory response and superior regenerative outcomes in skin wound healing and posttraumatic models of osteoarthritis. The current study was designed to explore if selective genetic or pharmacological inhibition of the non-canonical gp130-Y814/SFK signaling reduces systemic chronic inflammation and multimorbidity in a high-fat diet (HFD)-induced model of accelerated aging. F814 mice showed significantly reduced inflammatory response to HFD in adipose and liver tissue, with significantly reduced levels of systemic inflammation compared to wild type mice. F814 mice were also protected from HFD-induced bone loss and cartilage degeneration. Pharmacological inhibition of gp130-Y814/SFK in mice on HFD mirrored the effects observed in F814 mice on HFD; furthermore, this pharmacological treatment also demonstrated a marked increase in physical activity levels and protective effects against inflammation-associated suppression of neurogenesis in the brain tissue compared to the control group. These findings suggest that selective inhibition of SFK signaling downstream of gp130 receptor represents a promising strategy to alleviate systemic chronic inflammation. Increased degenerative changes and tissue senescence are inevitable in obese and aged organisms, but we demonstrated that the systemic response and inflammation-associated multi-morbidity can be therapeutically mitigated.

cell biology↗

bioRxiv2024

Network computations underlying learning from symbolic gains and losses

Reinforcement learning (RL), particularly in primates, is often driven by symbolic outcomes. However, it is usually studied with primary reinforcers. To examine the neural mechanisms underlying learning from symbolic outcomes, we trained monkeys on a task in which they learned to choose options that led to gains of tokens and avoid choosing options that led to losses of tokens. We then recorded simultaneously from the orbitofrontal cortex (OFC), ventral striatum (VS), amygdala (AMY), and the mediodorsal thalamus (MDt). We found that the OFC played a dominant role in coding token outcomes and token prediction errors. The other areas contributed complementary functions with the VS coding appetitive outcomes and the AMY coding the salience of outcomes. The MDt coded actions and relayed information about tokens between the OFC and VS. Thus, OFC leads the process of symbolic reinforcement learning in the ventral frontostriatal circuitry.

neuroscience↗

bioRxiv2024

Whole-genome resequencing revealed the Origin and Domestication of Chinese Domestic Rabbits

The evolutionary and genetic origins of Chinese indigenous rabbits (Oryctolagus cuniculus) remain largely unclear, despite being among the most recently domesticated animals. We sequenced the whole genomes of 142 individual rabbits and collected 25 resequencing accessions from the NCBI, representing six Chinese indigenous breeds, three other domesticated breeds (serving as a bridge between European wild-type and Chinese domestic populations), and two wild rabbit populations from the Iberian Peninsula and Southern France. Population and demographic analyses suggest that Chinese domestic rabbits are most likely descendants of O. c. cuniculus, native to France 800-1500 years ago. These rabbits likely first arrived in the southeast coastal areas of China through trade before spreading to inland regions. Additionally, there may be other origins for Chinese domestic rabbits. We observed considerable variation in the genetic makeup of maternal ancestry between Chinese domestic rabbits and European wild populations, with Chinese rabbits possessing unique mitochondrial haplotypes. Our analysis also highlights selective sweeps on genes affecting brain and neuronal development, which may have been under strong positive selection during domestication; genes related to starch digestion and fat metabolism, suggesting an evolutionary adaptation to digest high-starch diets; and the white coat phenotype in rabbits, resulting from selection at the melanogenesis-associated transcription factor locus. Overall, our data provide comprehensive insights into the origin and domestication of rabbits and lay the foundation for genome-based breeding.

evolutionary biology↗

bioRxiv2024

Thymic dendritic cell-derived IL-27p28 promotes the establishment of functional bias against IFN-γ production in newly generated CD4+ T cells through STAT1-related epigenetic mechanisms

The newly generated CD4 single-positive (SP) T lymphocytes are featured by enhanced IL-4 but repressed IFN-{gamma} production. The mechanisms underlying this functional bias remain elusive. Previous studies have reported that CD4+ T cells from mice harboring DC-specific deletion of IL-27p28 display an increased capacity of IFN-{gamma} production upon TCR stimulation. Here we demonstrated that similarly altered functionality occurred in CD4SP thymocytes, recent thymic emigrants (RTEs), as well as naive T cells from either Cd11c-p28f/f mice or mice deficient in the subunit of IL-27 receptor. Therefore, DC-derived IL-27p28-triggered, IL-27R-mediated signal is critically involved in the establishment of functional bias against IFN-{gamma} production during their development in the thymus. Epigenetic analyses indicated reduced DNA methylation of the Ifng locus and increased trimethylation of H3K4 at both Ifng and Tbx21 loci in CD4SP thymocytes from Cd11c-p28f/f mice. Transcriptome profiling demonstrated that Il27p28 ablation resulted in the coordinated up-regulation of STAT1-activated genes. Concurrently, STAT1 was found to be constitutively activated. Moreover, we observed increased accumulation of STAT1 at the Ifng and Tbx21 loci and a strong correlation between STAT1 binding and H3K4me3 modification of these loci. Of note, Il27p28 deficiency exacerbated the autoimmune phenotype of Aire-/- mice. Collectively, this study reveals a novel mechanism underlying the functional bias of newly generated CD4+ T cells and the potential relevance of such a bias in autoimmunity. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/583138v2_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@e63531org.highwire.dtl.DTLVardef@1ae35ddorg.highwire.dtl.DTLVardef@525cbaorg.highwire.dtl.DTLVardef@145beae_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

In silico identification of putative causal genetic variants

Understanding the causal genetic architecture of complex phenotypes will fuel future research into disease mechanisms and potential therapies. Here, we illustrate the power of a novel framework: it detects, starting from summary statistics, and across the entire genome, sets of variants that carry non-redundant information on the phenotypes and are therefore more likely to be causal in a biological sense. The approach, implemented in open-source software, is also computationally efficient, requiring less than 15 minutes on a single CPU to perform genome-wide analysis. Through extensive genome-wide simulation studies, we show that the method can substantially outperform existing methods in false discovery rate control, statistical power and various fine-mapping criteria. In applications to a meta-analysis of ten large-scale genetic studies of Alzheimers disease (AD), we identified 82 loci associated with AD, including 37 additional loci missed by conventional GWAS pipeline. Massively parallel reporter assays and CRISPR-Cas9 experiments have confirmed the functionality of the putative causal variants our method points to. Finally, we retrospectively analyzed summary statistics from 67 large-scale GWAS for a variety of phenotypes. Results reveal the methods capacity to robustly discover additional loci for polygenic traits and pinpoint potential causal variants underpinning each locus beyond conventional GWAS pipeline, contributing to a deeper understanding of complex genetic architectures in post-GWAS analyses.

genetics↗