Biology subjects

Tian, S.

Publications and source records attributed to Tian, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Genetic circuit rewiring underlies a lineage-specific patterning machinery on butterfly wings

Phenotypes evolve through changes in gene regulatory networks (GRNs), but how changes in network topology contribute to phenotypic evolution is still poorly understood. Butterfly wing color patterns provide a tractable system to answer this question. Here, we compared the expression of four color pattern genes, WntA, pdm3, ivory, and Optix, in five nymphalid butterflies, and tested their regulatory connections through genetic perturbations in three species spanning 80 million years of divergence. We found broadly conserved 1) regulatory hierarchy linking early pattern instruction via WntA signaling to subsequent color readout via ivory and Optix, 2) positive autoregulation in WntA signaling, and 3) positive regulation from WntA signaling to pdm3. Notably, we discovered lineage-specific negative feedback from pdm3 to WntA signaling in Vanessa cardui, which closes a reciprocal WntA-pdm3 feedback loop that refines complex pattern elements. We show that developmental programs can evolve by rewiring internal interactions among pre-existing GRN nodes, emphasizing the importance of network topology in phenotypic evolution.

evolutionary biology↗

bioRxiv2026

Dietary fiber-type-specific gut microbiome preconditioning drives differential susceptibility to sporadic colon cancer development

Background: Dietary fiber intake is broadly associated with reduced colorectal cancer (CRC) risk, yet processed fiber supplements exert inconsistent and occasionally opposing effects on colon tumorigenesis. How structurally distinct dietary fibers differentially shape the gut microbiome-metabolome axis to influence carcinogenic susceptibility remains poorly understood. Objective: To determine whether structurally distinct dietary fibers differentially modulate colon tumor development and characterize the underlying gut microbiome and metabolic mechanisms. Design: Four-week-old male mice were maintained on low-fiber control or fiber-supplemented diets (7.5%w/w: cellulose, agar, pectin, or inulin) for 28 weeks and received eight intraperitoneal azoxymethane injections (AOM; 7.5 mg/kg). Temporal fecal microbiomes were profiled by 16S-rRNA sequencing, cecal metabolites quantified by H-NMR spectroscopy, and microbiome-metabolome interactions assessed by co-occurrence networks. Results: Refined inulin supplementation markedly elevated colon tumor incidence (~70%) compared with all other groups (~10-20%), and cecal extracts from inulin-fed mice promoted HT29 cancer-cell proliferation. Longitudinal microbiome profiling identified 36 inulin-specific microbial signatures converging on two axes: depletion of SCFAs and fermentation cross-feeding taxa and reprogramming of amino acid and nitrogen metabolism. Metabolomics confirmed succinate, fumarate, and lactate accumulation alongside propionate and amino acid depletion exclusively under AOM conditions, with no differences in carcinogen-naive animals. Two stable co-occurrence hubs were identified exclusively in AOM-treated animals, structurally integrating both functional axes. Conclusion: Inulin supplementation preconditions the gut microbiome toward functional vulnerability, characterized by disrupted fermentation throughput and reprogrammed amino acid metabolism, that is amplified by carcinogen exposure into a tumor-promoting ecosystem, providing a mechanistic basis for the disproportionately higher tumor prevalence in inulin-fed animals.

microbiology↗

bioRxiv2026

A binuclear copper enzyme platform for enantioconvergent radical (pseudo)halogenation

Despite their intriguing native metalloenzymology, naturally occurring copper enzymes remain largely underexploited for new-to-nature biocatalytic reactions. Herein, we report the systematic investigation and reprogramming of natural copper enzymes to catalyze unnatural free radical (pseudo)halogenation reaction in a highly enantioselective fashion. Evaluating Cu enzymes in the decarboxylative azidation of redox-active esters revealed activity across multiple Cu enzyme families, with type III binuclear Cu enzymes, particularly the Bacillus megaterium tyrosinase (BmTyr), exhibiting superior activity and enantioselectivity across both stabilized and unstabilized alkyl radicals upon further engineering. The strong halide binding affinity of the binuclear Cu system also enabled challenging enantioconvergent bromination, chlorination and isothiocyanation reactions, which remained inaccessible to repurposed nonheme Fe enzymes. Further EPR and UV-visible spectroscopic analyses confirmed the coupled binuclear nature of wild-type and engineered bacterial tyrosinases and provided insights into the origin of their enhanced activity. Collectively, this study establishes binuclear copper enzymes as a powerful platform for new-to-nature stereoselective radical reactions, expanding the scope of metalloenzyme catalysis beyond mononuclear systems.

biochemistry↗

bioRxiv2026

A multi-tissue epigenomic atlas links the sheep non-coding genome to domestication and complex traits

Non-coding regulatory variation drives complex traits, domestication, and evolutionary adaptation, yet the sheep genome lacks high-resolution functional annotation. Here we present SheepEpimap, a multi-tissue regulatory atlas harmonizing 516 CUT&Tag histone modifications, ATAC-seq, and RNA-seq datasets across 43 adult tissues in sheep. We annotated 2.93 million cis-regulatory elements, yielding 557,441 enhancer-gene pairs and 145,407 variants with allele-specific effects. By training a sequence-to-function deep-learning model, we decoded the base-pair syntax of chromatin accessibility, annotated transcription factor motif instances genome-wide, and constructed 12,210 tissue-specific gene regulatory networks (GRNs). Integrating this resource with multi-tissue expression quantitative trait loci, selection sweeps, and genome-wide association studies prioritized non-coding variants driving domestication and complex traits. Finally, cross-species analysis revealed that sequence-conserved, tissue-matched enhancers were significantly enriched in the heritability of complex traits and diseases in humans. In summary, SheepEpimap (https://genome.ucsc.edu/s/mengzhu/SheepEpimap) provides an open-access foundational ecosystem for sheep functional genomics, precision breeding, and comparative biology.

genetics↗

bioRxiv2026

Coevolution-driven reconstruction of multi-taxa siderophore interaction networks reveals topological diversity of microbial exploitation

Microbial communities are shaped by secreted metabolites that mediate ecological interactions, yet predicting these interactions from genomic sequences remains difficult, because the specific recognition between co-functional metabolites (CFMs), such as siderophores, and their receptor proteins (Rec) cannot be inferred from gene annotation alone. This difficulty arises from three factors: the prevalence of Rec-mediated exploitation, the lack of high-accuracy functional annotations, and the absence of genomic co-localization between functionally paired CFM-Rec in Gram-positive bacteria. Here we present the Coevolution-based Interaction Model (CIM), an automated framework that maps specific CFM-Rec pairings directly from uncurated genomic datasets. Using a dynamic joint optimization strategy that accounts for exploitation asymmetry and avoids combinatorial explosion, CIM identifies functional pairings solely through evolutionary covariation. We validated this approach by reconstructing macroscale iron scavenging networks across nine bacterial taxa. Experiments confirmed that CIM can bridge genomic distances exceeding 3 Mb in the Gram-positive genus Rhodococcus to identify unlinked cognate receptors, and can accurately predict cross-utilization by exploiter strains despite substantial receptor sequence heterogeneity in Burkholderiaceae and Rhizobiaceae. Finally, topological analysis of the reconstructed networks shows that siderophore exploitation acts as a universal topological glue, fusing fragmented microbial populations into highly connected communities, and that the exploitability of siderophore production reverses depending on network modularity. CIM thus offers a scalable, sequence-to-ecology approach for predicting interactions mediated by secondary metabolites in microbial communities.

systems biology↗

bioRxiv2026

A GPX4 phosphorylation switch by FGFR1 guards against ferroptosis

Ferroptosis is driven by lipid peroxidation, yet the mechanisms by which cells rapidly adjust their sensitivity to ferroptosis in response to extracellular cues remain elusive. We identify a direct phosphorylation switch controlling the activity of glutathione peroxidase 4 (GPX4), the core ferroptosis regulator. The receptor tyrosine kinase FGFR1 directly binds and phosphorylates GPX4 at Tyr180/Tyr196 in a kinase-dependent manner, requiring its Tyr730 as a docking site. This phosphorylation enhances GPX4s catalytic activity and suppresses ferroptosis. In cardiac ischemia/reperfusion injury, the FGFR1-GPX4 axis is suppressed, and a selective FGFR1 agonist (FGF-1{Delta}NT) reactivates it to protect against ferroptosis-mediated damage. Critically, a phosphorylation-deficient GPX4 knock-in mouse exhibits hypersensitivity to injury and non-responsive to this agonist, proving that GPX4 phosphorylation is essential. Our findings reveal a rapid mechanism for regulating ferroptosis via GPX4 tyrosine phosphorylation, directly linking receptor tyrosine kinase signaling to ferroptosis, and offering new strategies for treating ischemic-and other ferroptosis-associated diseases.

Cell Biology↗

bioRxiv2026

Intra-Complex Differential Transcription Strategies for Scaffold versus Effector Proteins

Scaffold-organized multi-protein complexes are major drivers of cellular regulatory pathways, but how the expression of their constituent genes is coordinated to support efficient assembly and cell-to-cell homeostasis remains poorly understood. Using snapTotal-seq data, this study addresses this issue at the transcription level through comparative analyses of stochastic transcription bursting - a major driver of expression level and primary source of its intrinsic cell-to-cell noise. We compared scaffold proteins and their effector partners in major regulatory multi-protein complexes: TNRC6A/B/C (in the miRISC complex) and CNOT1/2 (in the CCR4-NOT complex) in mRNA regulation; and AXIN1, APC, KSR2, AKAPs, DLG1, PATJ, HOMER1/2, and SQSTM1 in signal transduction. Our analyses reveal a shared strategy: compared to genes for active effector partner proteins and the general transcriptome, genes for structural scaffold proteins consistently utilize more frequent and smaller-sized bursting to achieve the fine tuning of a homeostatic expression level. This finding establishes a fundamental link between a proteins physical role within a regulatory complex and the transcriptional bursting kinetics of its gene.

Systems Biology↗

bioRxiv2026

Nitrosomes: protein language modeling and live-cell imaging reveal condensate-like nitrogenase organization in heterocysts

Biological nitrogen fixation in some filamentous cyanobacteria occurs in heterocysts, yet the subcellular organization of nitrogenase in these cells remains poorly defined. Using fluorescence microscopy of living Anabaena sp. PCC 7120, we found that a NifH-GFP fusion forms discrete puncta restricted to mature heterocysts, whereas constitutively expressed GFP in vegetative cells and a nifB-linked GFP reporter remained diffuse. To contextualize this phenotype, we built a homology-aware cyanobacterial condensate-prioritization framework across 31,028 proteins from seven proteomes, integrating ESM-2 embeddings, 27 biophysical features, and 44 curated condensate-associated positives. Because direct positives remain limited, we present the model as a ranking resource rather than a calibrated classifier. Under a deliberately conservative nitrogenase-withheld analysis that removed nitrogenase-family labels and homologous clusters from the training data, NifH retained a median rank in the highest-scoring 4.8% of cyanobacterial proteins. catGRANULE 2.0 also assigned high scores to nitrogenase iron proteins, while having only modest rank concordance to the whole atlas. Together, these data identify heterocyst-restricted NifH-GFP puncta as evidence of sub-cellular spatial organization and provide a curated resource for prioritizing cyanobacterial condensate candidates, some of which are also important for nitrogen fixation.

molecular biology↗

bioRxiv2026

Synergy of RNA Concentration, RNA Binding Proteins, and RNA Palindrome Drives clustering of oskar mRNA in vivo

Organization of mRNAs into clusters has been observed in many cellular contexts, yet the features that govern this process in vivo remain poorly understood. Using super-resolution microscopy, single-mRNA imaging, and genetic perturbations, we investigated how mRNA concentration, the double-stranded RNA-binding protein Staufen (Stau), and intermolecular base-pairing driven by an RNA palindrome influence clustering of oskar (osk) mRNA in Drosophila embryos. We find that these factors collectively optimize osk clustering by promoting its dimerization and subsequent oligomerization. Both processes depend on all three factors, although oligomerization is more sensitive to their perturbation, indicating that the driving force for osk oligomerization is partially distinct from that governing dimerization. Furthermore, expression of Stau nearly doubles the likelihood of osk dimerization whereas disruption of the palindrome reduces it fourfold indicating that the presence of Stau and the palindrome lowers the concentration threshold of osk mRNA required for dimerization. Notably, insertion of the osk palindrome into a reporter mRNA markedly increased its association with the endogenous osk, further supporting the conclusion that the palindrome potently drives intermolecular base pairing. Importantly, this experiment also identified the palindrome as the major contributor to heterotypic clustering between the endogenous osk and the reporter mRNA. Finally, computational analyses identified a subset of early embryonic mRNAs predicted to harbor palindromes similar to those found in osk. Among these, eIF3a mRNA emerged as a candidate whose clustering may likewise be driven by intermolecular base pairing. Together, our findings raise the possibility that mRNA clustering driven by palindrome-mediated intermolecular base pairing may be more widespread than previously appreciated and may represent an important mechanism for controlling mRNA spatial organization during early Drosophila development.

molecular biology↗

bioRxiv2026

Parallel evolution of industrial melanism in the peppered moth: one locus, many alleles

The extent to which adaptation to environmental change occurs via single or multiple advantageous mutations remains an open question, which we examined by studying the spread of melanic forms of the peppered moth in Britain and continental Europe, in response to industrial coal pollution. In Britain, the darkest melanic form is due to the insertion of a transposable element (carb-TE) into a genomic region called ivory. Here, we characterize the spread of melanic forms in continental Europe from historical records and uncover the genetic basis of European melanism using genomic analyses of modern and museum specimens. We show that European melanism is also associated with variants at ivory, but with multiple alleles featuring structural variants, including several transposable elements, though not carb-TE. The primary central European melanic allele is a genetically dominant 805 base pair deletion (sollichau). Interestingly, melanic individuals with either sollichau (deletion) or carb-TE (insertion) alleles show elevated expression of ivory and its effector micro-RNA (mir-193) compared to non-melanic (typica) individuals, suggesting that contrasting structural variants in ivory have similar regulatory effects. A functional role for sollichau was corroborated, serendipitously, by its presence in a typica individual which also contains a linked deletion of mir-193, which is predicted to cancel the melanizing effect of the sollichau deletion. Our results support the idea that there can be many genetic origins of the same adaptive trait within a species, particularly one with a large effective population size and heterogeneous natural habitat, and when many mutations can give rise to the same phenotype.

evolutionary biology↗

bioRxiv2026

A biofidelic Goat Model of Traumatic Optic Neuropathy with Optic Canal Fracture via Transnasal Endoscopy

Traumatic optic neuropathy (TON) is a major cause of irreversible vision loss following blunt cranial trauma, yet the absence of clinically relevant large animal models that faithfully recapitulate human TON has significantly impeded translational research. Current rodent models do not reproduce optic canal fracture, a key injury mechanism in many patients with TON. Here, we combined high-fidelity finite element analysis (FEA) with iterative engineering to establish a reproducible goat model of TON. We first built a high-resolution human-head finite element model to characterize force transmission to the optic nerve. Across clinically relevant periorbital impacts, stress preferentially concentrated in the intracanalicular segment, reaching a peak force density of approximately 500 N/m2 at 50.6 ms, about fivefold higher than in the intraorbital segment. Simulations further showed that direct optic canal impact reproduced comparable intracanalicular stress with a markedly lower input force: 195 N, compared with 3900 N for periorbital impact. Guided by these insights, we developed transnasal endoscopic impact systems capable of inducing optic canal fractures in goats. TON was confirmed within 24 hours by a characteristic relative afferent pupillary defect (RAPD), and at 1 month post-injury goats (n = 14) exhibited a 10%-20% reduction in ganglion cell complex (GCC) thickness and 40%-65% reductions in flash visual evoked potential (FVEP) and pattern electroretinogram (PERG) amplitude ratios (all P [≤] 0.001), with structural and functional preservation of the fellow eye. This study presents a robust, standardized, and clinically relevant large-animal platform for investigating TON pathophysiology.

neuroscience↗

bioRxiv2026

GmEBS7a-E2 complex dissociation hyperactivates ERAD to impair plant immunity against Phytophthora pathogens

Endoplasmic reticulum-associated degradation (ERAD) pathways are crucial for maintaining plant development and stress responses. While ERAD has been extensively studied for its role in regulating responses to abiotic stress, its specific manipulation by eukaryotic pathogens stress remains unclear. Here, we reported that soybean GmEBS7a, a plant-specific ERAD component, is targeted and stabilized by a transmembrane domain-containing effector Avh131 from Phytophthora sojae. GmEBS7a enhances plant disease susceptibility by increasing ERAD efficiency and ER stress sensitivity. Mechanistically, Avh131 competitively disrupts the interaction with GmEBS7a and the ubiquitin-conjugating enzyme GmUBC32, reducing ubiquitination of GmEBS7a and subsequent inhibition of its degradation. These findings demonstrate that excessive ERAD triggered by stabilized GmEBS7a and its partnering E3 ligase impairs the plants response to biotic stress. Our study uncovers a fine-tuning of the ER protein-folding capacity to promote infection, thereby expanding our understanding of ER-centered immunity during plant-pathogen interactions.

immunology↗

bioRxiv2026

Wetting-mediated extracellular phase separation drives long-range cell adhesion

Cells must efficiently locate and engage for tissue formation and immune coordination, yet classical receptor-ligand binding is limited to nanometre distances and is inherently slow [1-3]. Here, we uncover a previously unrecognised physical principle, liquid-like adhesion by phase separation (LAPS). This process creates dynamic wetting layers on cell surfaces [4, 5], functioning as "liquid bridges" that enable robust, long-range cell capture across tens of micrometres. Remarkably, this wetting-mediated attraction remains effective at nanomolar concentrations--conditions where bulk phase separation would not be expected--and facilitates high-fidelity cell sorting through competitive wetting. By integrating aqueous two-phase systems, endogenous proteins (Galectin-3, CCL5), and fluid-particle-dynamics simulations [6], we demonstrate that extracellular liquid-liquid phase separation not only mediates long-range cell capture but also acts as a physical catalyst for contact-dependent signaling. These findings establish extracellular phase separation as a key physical principle complementing molecular recognition in multicellular systems, offering new opportunities for understanding immune response, tissue morphogenesis, and therapeutic strategies targeting the extracellular environment [7, 8].

biophysics↗

bioRxiv2025

Conserved RNA helicase Vasa regulates ribonucleoprotein condensates through protein interaction and mRNA recruitment

Germlines contain ribonucleoprotein condensates known as germ granules, which concentrate proteins and mRNAs essential for animal development. Vasa, a conserved DEAD-box RNA helicase, is a core and highly concentrated constituent of germ granules. However, its roles within these structures remain poorly understood. Here, we use Drosophila germ granules as a model system to address this question. Applying in vivo and human cell systems, we found that condensation of Oskar (Osk) protein, which nucleates germ granules, occurred independently of Vasa. However, in oocytes lacking detectable Vasa protein, Osk formed aggregated condensates regardless of the eGFP tag. Furthermore, Osk-eGFP showed minimal recovery as measured by fluorescence recovery after photobleaching (FRAP) indicating that its exchange between condensates and their surroundings was greatly reduced in the absence of Vasa. Supporting this result, co-expression of Vasa increased the FRAP recovery of Osk-eGFP condensates and reduced Osk-eGFP partitioning into them in cells. This effect required the interaction between Vasa and Osk, suggesting that by binding Osk, Vasa modulates Osks phase behavior and its condensate material properties. Super-resolution microscopy further revealed that Vasa is required for germ granule mRNA localization to Osk condensates in vivo. Co-expression of Vasa with Osk-eGFP is necessary and sufficient to recruit germ granule mRNAs to condensates in cells. Although this activity depends on Vasa-Osk interaction, the interaction itself is not sufficient. Notably, localization of a conserved germ granule mRNA nanos reduced the FRAP recovery of Osk-eGFP condensates in cells, partially counteracting Vasas effect. Collectively, our findings uncovered a novel function of the DEAD-box RNA helicase Vasa in regulating the material properties of Osk condensates through coordinated protein-protein and protein-mRNA interactions. Four highlightsO_LIVasa modulates the material properties of Oskar ribonucleoprotein condensates in fly oocytes and human cells. C_LIO_LIVasa modulates condensate material properties through its interaction with Oskar. C_LIO_LImRNA localization to Oskar condensates requires Vasa and Vasa-Oskar interaction. C_LIO_LInanos mRNA localization counteracts Vasas enhancement of Oskar exchange between condensates and their surroundings. C_LI

molecular biology↗

bioRxiv2025

Ethylene receptors are functionally conserved in calcium permeability across the green lineage

The gaseous hormone ethylene plays a key role in regulating plant growth and stress responses. Although Ca{superscript 2} has long been implicated in ethylene signaling, the identity of molecules controlling Ca{superscript 2} permeability involved has remained elusive. Here we show that Arabidopsis ethylene receptors ETR1 and ERS1 are Ca2+ permeable, and that ETR1 mediates ethylene-induced cytosolic Ca2+ increase and regulates hypocotyl elongation. Homologs of ETR1 from eight land plant and algal species also exhibit Ca{superscript 2} permeability, suggesting an evolutionarily conserved function. We further demonstrate ethylene enhances the Ca2+ permeability of ETR1 and its homologue from the charophyte Klebsormidium flaccidum. These findings uncover a previously unrecognized but conserved role of ethylene receptors in Ca{superscript 2} permeability regulation in the green lineage, with broad implications for Ca{superscript 2} signaling in plant development and environmental adaptation.

plant biology↗

bioRxiv2025

Rationally Engineered Coronavirus-mimicking Protein Nanocage Platform for Glioblastoma Targeted Delivery and Immunity Regulation

Glioblastoma (GBM) is one of the most aggressive and treatment-resistant brain tumors, owing to the dual challenges of the blood-brain barrier (BBB) and a profoundly immunosuppressive tumor microenvironment. However, few existing strategies are capable of simultaneously overcoming these two barriers, underscoring a critical scientific gap and the need for innovative therapeutic platforms that enable both effective BBB traversal and tumor immune reprogramming. Here, we present a coronavirus-mimicking protein nanocage platform (EcomPC) derived from Thermotoga maritima encapsulin, rationally engineered for the targeted and sustained delivery of interferon- (IFN-) to GBM lesions. Through strategic insertion of flexible linkers, cysteine-to-serine mutations, and modular surface functionalization via SpyTag/SpyCatcher chemistry, EcomPC enables intracellular self-assembly of IFN- and glioma-specific targeting. In orthotopic GBM models, EcomPC-IFN demonstrates efficient BBB translocation, selective tumor accumulation, and potent anti-tumor efficacy. Mechanistically, localized IFN- release induces tumor cell apoptosis and reprograms the immune microenvironment--characterized by increased CD8 T cell infiltration, decreased Foxp3 regulatory T cells, and a favorable chemokine shift. These therapeutic effects are not recapitulated by free IFN- or untargeted nanocages, underscoring the essential role of both structural mimicry and ligand-guided delivery. Collectively, this work establishes EcomPC as a programmable, virus-inspired protein delivery platform capable of overcoming key physiological barriers in brain tumor immunotherapy, and lays the foundation for its broader application in CNS-targeted biologic delivery.

bioengineering↗

bioRxiv2025

A tale of three types of internal object representations in the human brain

Perception and mental imagery are widely thought to rely on overlapping neural representations, giving rise to perception-like visual experiences during imagery generation. However, such overlap, by itself, is agnostic to the nature of the underlying neural geometry for both perception and imagery. Here we addressed this question by comparing visualizers and individuals with congenital aphantasia using fMRI, representational similarity analysis, and multimodal deep neural network models to probe different types of neural geometry. Despite comparable behavioral performance and perception-imagery generalization of neural object representations in the ventral occipitotemporal cortex, the two groups exhibited systematically different object representational geometries already in the perceptual encoding phase. Visual-similarity-aligned geometry was selectively reduced in the left lateral occipitotemporal cortex of individuals with aphantasia during perceptual encoding, before imagery generation, and its expression during imagery covaried with imagery vividness. In contrast, language-relation-aligned geometry was preserved across groups during both perception and imagery. Together, these findings suggest that subjective imagery experience is associated with the geometry of neural object representations during both perception and imagery, and that representations within perception- imagery cross-decoding regions comprise heterogeneous components rather than a unitary shared neural code.

neuroscience↗

bioRxiv2025

BioTransformer4.0 a comprehensive computational tool for small molecule metabolism prediction

BioTransformer 4.0, the successor to BioTransformer 3.0, is a freely available in silico metabolism prediction tool. It integrates both knowledge-based and machine learning approaches to predict metabolites for small molecules using one of seven modules: abiotic, environmental, CYP450, phase II, enzyme commission-based, human gut microbial, and all human metabolism. It also provides a customizable sequence prediction module that allows users to simulate multi-step metabolic transformations by chaining among the first six different modules. BioTransformer 4.0 can make predictions more efficiently and accurately than the previous version, as it includes more than 130 new reaction rules, and also an optional validation module to improve the efficiency by restricting the number of predicted metabolites, due to their similarity among real human metabolites. We evaluated its performance by running the six-step all-human metabolism prediction on the DrugBank dataset of 2,457 known biotransformations, and the PhytoHub dataset of 633 known biotransformations - achieving recall values of 87.2% (resp., 91.6%) for the DrugBank (resp., PhytoHub) datasets.

bioinformatics↗