Biology subjects

Liu, H.

Publications and source records attributed to Liu, H..

At least 721 records · Page 40Linked to original sources

bioRxiv2021

Genome-wide development of lncRNA-derived-SSR markers for Dongxiang wild rice (Oryza rufipogon Griff.)

Dongxiang wild rice (Oryza rufipogon Griff., DXWR) is the northernmost distributed common wild rice found in the world. It contains a large number of agronomically valuable genes, which makes it a natural gene pool for rice breeding. Molecular markers, especially simple repeat sequence (SSR) markers, play important roles in crop breeding. Although a large number of SSR markers have been developed, most of them are derived from the genome coding sequences, rarely from non-coding sequences. Meanwhile, long non-coding RNAs (lncRNAs), which are derived from the transcription of non-coding sequences, play vital roles in plant growth, development and stress responses. In this study, 1878 SSR loci were detected from the lncRNA sequences of DXWR, and 1258 lncRNA-derived-SSR markers were developed on the genome-wide scale. To verify the validity and applicability of these markers, 72 pairs of primers were randomly selected to test 44 rice materials. The results showed that 42 (58.33%) pairs of primers have abundant polymorphism among these rice materials; the polymorphism information content (PIC) values ranged from 0.04 to 0.87 with an average of 0.50; the genetic diversity index of SSR loci varied from 0.04 to 0.88 with an average of 0.56; and the number of alleles per marker ranged from 2 to 11 with an average of 4.36. Thus, we concluded that these lncRNA-derived-SSR markers are a very useful source for future basic and applied research, including genetic diversity analysis, QTL mapping, and molecular breeding programs, to make good use of the elite lncRNA genes from DXWR.

plant biology↗

bioRxiv2021

Ecological dynamics of the gut microbiome in response to dietary fiber

Dietary fibers are generally thought to benefit intestinal health. Their impacts on the composition and metabolic function of the gut microbiome, however, vary greatly across individuals. Previous research showed that each individuals response to fibers depends on their baseline gut microbiome, but the ecology driving microbiota remodeling during fiber intake remained unclear. Here, we studied the long-term dynamics of gut microbiome and short-chain fatty acids (SCFAs) in isogenic mice with distinct microbiota baselines fed with the fermentable fiber inulin compared to the non-fermentable fiber cellulose. We found that inulin produced generally rapid response followed by gradual stabilization to new equilibria, and those dynamics were baseline-dependent. We parameterized an ecology model from the timeseries data, which revealed a group of bacteria whose growth significantly increases in response to inulin. and whose baseline abundance and interspecies competition explains the baseline-dependence of microbiome density and community composition dynamics. Fecal levels of of SCFAs, such as propionate, is associated with the abundance of inulin responders, yet inter-individual variation of gut microbiome impedes the prediction of SCFAs by machine learning models. Finally, we showed that our methods and major findings are generalizable to dietary resistant starch. This study emphasizes the importance of ecological modeling to understand microbiome responses to dietary changes and the need for personalized interventions.

ecology↗

bioRxiv2021

Screening of cell-virus, cell-cell, gene-gene interactions among kingdoms of life at single cell resolution

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) issued a significant and urgent threat to global health. The exact animal origin of SARS-CoV-2 remains obscure and understanding its host range is vital for preventing interspecies transmission. Previously, we have assessed the target cell profiles of SARS-CoV-2 in pets, livestock, poultry and wild animals. Herein, we expand this investigation to a wider range of animal species and viruses to provide a comprehensive source for large-scale screening of potential virus hosts. Single cell atlas for several mammalian species (alpaca, hamster, hedgehog, chinchilla etc.), as well as comparative atlas for lung, brain and peripheral blood mononuclear cells (PBMC) for various lineages of animals were constructed, from which we systemically analyzed the virus entry factors for 113 viruses over 20 species from mammalians, birds, reptiles, amphibians and invertebrates. Conserved cellular connectomes and regulomes were also identified, revealing the fundamental cell-cell and gene-gene cross-talks between these species. Overall, our study could help identify the potential host range and tissue tropism of SARS-CoV-2 and a diverse set of viruses and reveal the host-virus co-evolution footprints.

cell biology↗

bioRxiv2021

N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2

The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in nearly 7 million deaths. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout, vaccine hesitancy, and inefficient vaccine-mediated protection. Immunoadjuvant compounds delivered intranasally can guide non-specific innate immune responses during the critical early stages of viral replication, reducing morbidity and mortality. N- dihydrogalactochitosan (GC) is a novel mucoadhesive immunostimulatory polymer of {beta}- 0-4-linked N-acetylglucosamine that is solubilized by the conjugation of galactose glycans with current applications as a cancer immunotherapeutic. We tested GC as a potential countermeasure for COVID-19. GC was well-tolerated and did not produce histopathologic lesions in the mouse lung. GC administered intranasally before and after SARS-CoV-2 exposure diminished morbidity and mortality in humanized ACE2 receptor expressing mice by up to 75% and reduced infectious virus levels in the upper airway. Fluorescent labeling of GC shows that it is confined to the lumen or superficial mucosa of the nasal cavity, without involvement of adjacent or deeper tissues. Our findings demonstrate a new application for soluble immunoadjuvants such as GC for preventing disease associated with SARS-CoV-2 and may be particularly attractive to persons who are needle-averse. IMPORTANCEThe ongoing COVID-19 pandemic necessitates new approaches to reduce disease caused by SARS-CoV-2. We tested the immunoadjuvant N-dihydrogalactochitosan (GC), used previously as an immunostimulant for tumor therapy and adjuvant for viral vaccines, as a potential COVID-19 countermeasure. When GC was administered before and after inoculation of a lethal dose of SARS-CoV-2 into the nose of humanized mice expressing an entry receptor for the virus, fewer mice showed weight loss and died compared to mice that received only the vehicle but no GC. GC-treated mice also had lower levels of infectious SARS-CoV-2 in their upper airway. These results suggest that GC may be a candidate to prevent or treat COVID-19. Single Sentence SummaryThe immunoadjuvant N-dihydrogalactochitosan diminishes SARS-CoV-2 disease in humanized ACE2 mice, representing a new countermeasure against COVID-19.

microbiology↗

bioRxiv2021

Intrinsically disordered pathogen effector alters the STAT1 dimer to prevent recruitment of co-transcriptional activators CBP/p300

Signal transducer and activator of transcription (STATs) proteins signal from cell-surface receptors to drive transcription of immune response genes. The parasite Toxoplasma gondii blocks STAT1-mediated gene expression by secreting the intrinsically disordered protein TgIST that traffics to the host nucleus, binds phosphorylated STAT1 dimers, and occupies nascent transcription sites that unexpectantly remain silenced. Here we define a core repeat region within internal repeats of TgIST that is necessary and sufficient to block STAT1-mediated gene expression. Cellular, biochemical, mutational, and structural studies demonstrate that the repeat region of TgIST adopts a helical conformation upon binding to STAT1 dimers. The binding interface is defined by a groove formed from two loops in the STAT1 SH2 domains that reorient during dimerization. TgIST binding to this newly exposed site at the STAT1 dimer interface altered its conformation and prevented recruitment of co-transcriptional activators, thus defining the mechanism of blocked transcription.

microbiology↗

bioRxiv2021

Gadolinium-free Magnetic Resonance Imaging of the Liver using an Oatp1-targeted Manganese(III) Porphyrin

Controversy surrounding gadolinium-based contrast agents (GBCAs) have rendered their continued utility highly contentious, but the liver-specific GBCA Gd(III) ethoxybenzyl-diethylene triamine pentaacetic acid (Gd(III)-EOB-DTPA) remains in use because it provides unique diagnostic information that could not be obtained by any other means. To address the need for an alternative liver-specific MRI contrast agent, we synthesized Mn(III) 20-(4-ethoxyphenyl) porphyrin-5,10,15-tricarboxylate (Mn(III)TriCP-PhOEt), which exhibited significantly higher r1 relaxivity than Gd(III)-EOB-DTPA, and targeted organic anion-transporting polypeptide 1 (Oatp1) channels as a biomarker of hepatocyte viability. Mn(III)TriCP-PhoEt increased the r1 relaxation rate of cells expressing rodent Oatp1a1 and human Oatp1b3, relative to control cells not expressing these liver channels. In mice, Mn(III)TriCP-PhoEt resulted in significant and specific increases in liver signal intensity on T1-weighted images, and significant decreases in liver T1 time relative to precontrast measurements. Our findings suggest that Mn(III)TriCP-PhOEt operates as a specific and sensitive MR contrast agent for in vivo liver imaging.

biophysics↗

bioRxiv2021

Widespread germline genetic heterogeneity of human ribosomal RNA genes

Polymorphism drives survival under stress and provides adaptability. Genetic polymorphism of ribosomal RNA (rRNA) genes derives from internal repeat variation of this multicopy gene, and from interindividual variation. A considerable amount of rRNA sequence heterogeneity has been proposed but has been challenging to estimate given the scarcity of accurate reference sequences. We identified four rDNA copies on chromosome 21 (GRCh38) with 99% similarity to recently introduced reference sequence KY962518.1. Pairwise alignment of the rRNA coding sequences of these copies showed differences in sequence and length. We customized a GATK bioinformatics pipeline using the four rDNA loci, spanning a total 145 kb, for variant calling. We employed whole genome sequencing (WGS) data from the 1000 Genomes Project phase 3 and analyzed variants in 2,504 individuals from 26 populations. Using the pipeline, we identified a total of 3,790 variant positions. The variants positioned non-randomly on the rRNA gene. Invariant regions included the promoter, early 5 ETS, 5.8S, ITS1 and certain regions of the 28S rRNA, and large areas of the intragenic spacer. 18S rRNA coding region had very few variants, while a total of 470 variant positions were observed on 28S rRNA. The majority of the 28S rRNA variants located on highly flexible human-expanded rRNA helical folds ES7L and ES27L, suggesting that these represent positions of diversity and are potentially under continuous evolution. These findings provide a genetic view for rRNA heterogeneity and raise the need to functional assess how the 28S rRNA variants affect ribosome functions.

bioinformatics↗

bioRxiv2021

Viral receptor profiles of masked palm civet revealed by single-cell transcriptomics

Civets are small mammals belonging to the family Viverridae. The masked palm civets (Paguma larvata) served as an intermediate host in the bat-to-human transmission of severe acute respiratory syndrome coronavirus (SARS-CoV) in 20031. Because of their unique role in the SARS outbreak, civets were suspected as a potential intermediate host of SARS-CoV-2, the etiological pathogen of the COVID-19 pandemic. Besides their susceptibility to coronaviruses, civets can also be infected by other viruses, such as canine distemper viruses2, parvoviruses3, influenza viruses4, etc. Regarding the ecological and economical role of civets, it is vital to evaluate the potential threats from different pathogens to these animals. Receptor binding is a necessary step for virus entry into host cells. Understanding the distribution of receptors of various viruses provides hints to their potential tissue tropisms. Herein, we characterized the cell atlas of five important organs (the frontal lobe, lung, liver, spleen and kidney) of masked palm civets (Paguma larvata) and described the expression profiles of receptor associated genes of 132 viruses from 25 families, including 16 viruses from 10 families reported before that can attack civets and 116 viruses with little infection record.

immunology↗

bioRxiv2021

Effects of four antibiotics on the diversity of the intestinal microbiota

Oral antibiotics remain the therapy of choice for severe bacterial infections; however, antibiotic use disrupts the intestinal microbiota, which increases the risk of colonization with intestinal pathogens. Currently, our understanding of antibiotic-mediated disturbances of the microbiota remains at the level of bacterial families or specific species, and little is known about the effect of antibiotics on potentially beneficial and potentially pathogenic bacteria under conditions of gut microbiota dysbiosis. Additionally, it is controversial whether the effects of antibiotics on the gut microbiota are temporary or permanent. In this study, we used 16S rRNA gene sequencing to evaluate the short-term and long-term effects of ampicillin, vancomycin, metronidazole, and neomycin on the murine intestinal microbiota by analyzing changes in the relative numbers of potentially beneficial and potentially pathogenic bacteria. We found that the changes in the intestinal microbiota reflected the antibiotics mechanisms of action and that dysbiosis of the intestinal microbiota led to competition between the different bacterial communities. Thus, destruction of bacteria with beneficial potential increased the abundance of bacteria with pathogenic potential. In addition, we found that these oral antibiotics had long-term negative effects on the intestinal microbiota and promoted the development of antibiotic-resistant bacterial strains. These results indicate that ampicillin, vancomycin, metronidazole, and neomycin have long-term negative effects and can cause irreversible changes in the diversity of the intestinal microbiota and the relative proportions of bacteria with beneficial potential and bacteria with pathogenic potential, thereby increasing the risk of host disease.

microbiology↗

bioRxiv2021

Rhodanese Rdl2 produces reactive sulfur species to scavenge hydroxyl radical and protect mitochondria

During aerobic respiration, mitochondria generate superoxide anion (O2*-), hydrogen peroxide (H2O2), and hydroxyl radical (HO*), and these reactive oxygen species (ROS) are detrimental to mitochondria. Mitochondrial damage is linked to a broad spectrum of pathologies such as Alzheimers disease, hemochromatosis, and diabetes. Mitochondria contain several enzymes for rapidly removing superoxide anion and hydrogen peroxide, but how they antagonize HO* is elusive, representing a loophole in the anti-ROS system. Herein, we discovered that Rhodanese 2 (Rdl2) is critical for maintaining the functionality and integrity of mitochondria under sub-lethal ROS stress in Saccharomyces cerevisiae. Rdl2 converts stable sulfur species (thiosulfate and dialkyl polysulfide) to reactive sulfane sulfur including persulfide that protects mitochondrial DNA via scavenging HO*. Surprisingly, hydrogen sulfide (H2S) promotes HO* production through stimulating the Fenton reaction, leading to increased DNA damage. Our study may reveal an ex-ante mean for antagonizing HO*, patching the loophole of the anti-ROS system in mitochondria.

microbiology↗

bioRxiv2021

Gut microbial diversity in stingless bees is linked to host wing size and is influenced by geography

Stingless bees are globally important social corbiculate bees, fulfilling critical pollination roles in many ecosystems; however, their gut microbiota, especially fungal communities, are not well characterized to date. We collected 121 bee samples from two species, Tetragonula carbonaria and Austroplebeia australis, across a distance of 1,200 km of eastern Australia, and analysed their gut microbiomes. We found that the gut bacterial richness of T. carbonaria was influenced by geography (latitude and longitude) and positively correlated to an established fitness indicator in insects; namely, host forewing length/size that relates to flight capacity of stingless bees. We characterized the core microbiomes of the two bees and found that they consisted of the bacterial taxa Snodgrassella, Lactobacillus, Acetobacteraceae and Bombella, and the fungal taxa Didymellaceae, Monocilium mucidum, Malassezia restricta and Aureobasidium pullulans. Both host species identity and management (wild or managed) significantly influenced the gut microbial diversity and composition, and similarity between colonies declined as the geographical distance between them increased. This result was also supported by our co-existing network analyses. Overall, we have thoroughly analysed stingless bee gut microbiomes, and provided novel evidence that T. carbonaria bees with larger wings or from more southern populations have higher microbial diversity in their guts. Originality-Significance StatementBeneficial interactions between insects and their microbial symbionts are pivotal for their fitness. In this study, we analysed the gut microbiomes of two stingless bee species, Tetragonula carbonaria and Austroplebeia australis, that are widespread and important pollinators in Australia. We characterized their gut microbiomes and detected a significant positive correlation between gut bacterial richness and host forewing size for T. carbonaria; the first time that gut microbial diversity has been linked to a morphological trait in stingless bees. Furthermore, we found that host species identity, management type (wild or managed) and geography all significantly influenced bee gut microbial diversity and composition, and were able to describe both bacterial and fungal core microbial taxa. This study reveals novel understandings of stingless bee gut microbiomes and provides the basis for utilizing microbial strategies to maintain colony health.

ecology↗

bioRxiv2021

ASER: Animal Sex Reversal database

Sex reversal, representing extraordinary sexual plasticity during the life cycle, not only triggers reproduction in animals but also affects reproductive and endocrine system-related diseases and cancers in humans. Sex reversal has been broadly reported in animals, however, an integrated resource hub of sex reversal information is still lacking. Here, we constructed a comprehensive database named ASER by integrating sex reversal-related data of 18 species from Teleostei to Mammals. We systematically collected 40,018 published papers and mined the Sex Reversal-associated Genes (SRGs), including their regulatory networks, from 1,611 core papers. We annotated homologous genes and computed conservation scores for whole genomes across the 18 species. Furthermore, we collected 206 available RNA-seq data and investigated the expression dynamics of SRGs during sex reversal or sex determination processes. In addition, we manually annotated 551 ISH images of SRGs from the literature and described their spatial expression in the gonads. Collectively, ASER provides a unique and integrated resource for researchers to query and reuse organized data to explore the mechanisms and applications of SRGs in animal breeding and human health. The ASER database is publicly available at http://aser.ihb.ac.cn/.

zoology↗

bioRxiv2021

ARID1A loss derepresses human endogenous retrovirus-H to modulate BRD4-dependent transcription

The transposable elements (TEs) through evolutionary exaptation have become an integral part of human genome, offering ample regulatory sequences and shaping chromatin 3D architecture. While the functional impacts of TE-derived sequences on early embryogenesis are recognized, their role in malignancy has only started to emerge. Here we show that many TEs, especially the pluripotency-related endogenous retrovirus H (HERVH), are abnormally activated in colorectal cancer (CRC) samples. The transcriptional upregulation of HERVH is associated with mutations of several tumor suppressors including ARID1A. Knockout of ARID1A in CRC cells leads to increased accessibility at HERVH loci and enhanced transcription, which is dependent on ARID1B. Suppression of HERVH in CRC cells and patient-derived organoids impairs tumor growth. Mechanistically, HERVH transcripts colocalize with nuclear BRD4 foci, modulate their dynamics, and co-regulate many target genes. Altogether, we uncover a critical role for ARID1A in restraining HERVH, which can promote tumorigenesis by stimulating BRD4-dependent transcription when ARID1A is mutated.

cancer biology↗

bioRxiv2021

A novel flight style allowing the smallest featherwing beetles to excel

Flight speed generally correlates positively with animal body size1. Surprisingly, miniature featherwing beetles can fly at speeds and accelerations of insects three times as large2. We show here that this performance results from a previously unknown type of wing motion. Our experiment combines three-dimensional reconstructions of morphology and kinematics in one of the smallest insects, Paratuposa placentis (body length 395 m). The flapping bristled wing follows a pronounced figure-eight loop that consists of subperpendicular up and down strokes followed by claps at stroke reversals, above and below the body. Computational analyses suggest a functional decomposition of the flapping cycle in two power half strokes producing a large upward force and two down-dragging recovery half strokes. In contrast to heavier membranous wings, the motion of bristled wings of the same size requires little inertial power. Muscle mechanical power requirements thus remain positive throughout the wing beat cycle, making elastic energy storage obsolete. This novel flight style evolved during miniaturization may compensate for costs associated with air viscosity and helps explain how extremely small insects preserved superb aerial performance during miniaturization. Incorporating this flight style in artificial flappers is a challenge for designers of micro aerial vehicles.

zoology↗

bioRxiv2021

Probing Affinity, Avidity, Anti-Cooperativity, and Competition in Antibody and Receptor Binding to the SARS-CoV-2 Spike by Single Particle Mass Analyses

Determining how antibodies interact with the spike (S) protein of the SARS-CoV-2 virus is critical for combating COVID-19. Structural studies typically employ simplified, truncated constructs that may not fully recapitulate the behaviour of the original complexes. Here, we combine two single particle mass analysis techniques (mass photometry and charge-detection mass spectrometry) to enable measurement of full IgG binding to the trimeric SARS-CoV-2 S ectodomain. Our experiments reveal that antibodies targeting the S-trimer typically prefer stoichiometries lower than the symmetry-predicted 3:1 binding. We determine that this behaviour arises from the interplay of steric clashes and avidity effects that are not reflected in common antibody constructs (i.e. Fabs). Surprisingly, these sub-stoichiometric complexes are fully effective at blocking ACE2 binding despite containing free receptor binding sites. Our results highlight the importance of studying antibody/antigen interactions using complete, multimeric constructs and showcase the utility of single particle mass analyses in unraveling these complex interactions.

immunology↗

bioRxiv2021

TRAF2, an innate immune sensor, reciprocally regulates mitophagy and inflammation to maintain cardiac myocyte homeostasis.

Mitochondrial damage triggers cell death signaling with catastrophic consequences in long-lived and irreplaceable cells, such as cardiac myocytes. Sensing of leaked mitochondrial DNA upon mitochondrial damage is also a potent trigger of inflammation. Whether the innate immune response pathways monitor mitochondrial damage in mitochondria-rich cardiac myocytes to prevent inflammation and cell death, remains unknown. TRAF2, an adaptor protein downstream of innate immune receptors, localizes to the mitochondria in the unstressed heart, with increased mitochondrial targeting in cardiomyopathic human hearts and after cardiac ischemia-reperfusion injury in mice. Inducible cardiomyocyte-specific deletion of TRAF2 in young adult mice impairs mitophagy with rapid decline in mitochondrial quality, upregulates TLR9 expression in cardiac myocytes, and results in inflammation and cell death manifesting as a fulminant cardiomyopathy. Preventing TLR9-mediated mitochondrial DNA sensing and resultant inflammation provides a short-term reprieve from cardiomyopathy, but persistence of damaged mitochondria results in long-term recrudescence. Restoration of wild-type TRAF2, but not the E3 ubiquitin ligase deficient mutant, improves mitochondrial quality and rescues cardiomyopathy to restore homeostasis. Thus, the innate immune response acts via TRAF2 as the first line of defense against mitochondrial damage by orchestrating homeostatic mitophagy to dampen myocardial inflammation and prevent cell death.

cell biology↗

bioRxiv2021

Improved SNV discovery in barcode-stratified scRNA-seq alignments

Single cell SNV analysis is an emerging and promising strategy to connect cell-level genetic variation to cell phenotypes. At the present, SNV detection from 10x Genomics scRNA-seq data is typically performed on the pooled sequencing reads across all cells in a sample. Here, we assess the gain of information of SNV assessments from individual cell scRNA-seq data, where the alignments are split by barcode prior to the variant call. For our analyses we use publicly available sequencing data on the human breast cancer cell line MCF7 cell line generated at consequent time-points during anti-cancer treatment. We analyzed SNV calls by three popular variant callers - GATK, Strelka2 and Mu-tect2, in combination with a method for cell-level tabulation of the sequencing read counts bearing SNV alleles - SCReadCounts. Our analysis shows that variant calls on individual cell alignments identify at least two-fold higher number of SNVs as compared to the pooled scRNA-seq. We demonstrate that scSNVs exclusively called in the single cell alignments (scSNVs) are substantially enriched in novel genetic variants and in coding functional annotations, in particular, stop-codon and missense substitutions. Furthermore, we find that the expression of some scSNVs correlates with the expression of their harbouring gene (cis-scReQTLs). Overall, our study indicates an immense potential of SNV calls from individual cell scRNA-seq data and emphasizes on the need of cell-level variant detection approaches and tools. Given the growing accumulation of scRNA-seq datasets, cell-level variant assessments are likely to significantly contribute to the understanding of the cellular heterogeneity and the relationship between genetics variants and functional phenotypes. In addition, cell-level variant assessments from scRNA-seq can be highly informative in cancer where they can help elucidate somatic mutations evolution and functionality.

genomics↗

bioRxiv2021

Combining Multi-Dimensional Molecular Fingerprints to Predict hERG Cardiotoxicity of Compounds

At present, drug toxicity has become a critical problem with heavy medical and economic burdens. acLQTS (acquired Long QT Syndrome) is acquired cardiac ion channel disease caused by drugs blocking the hERG channel. Therefore, it is necessary to avoid cardiotoxicity in the drug design and computer models have been widely used to fix this plight. In this study, we present a molecular fingerprint based on the molecular dynamic simulation and uses it combined with other molecular fingerprints (multi-dimensional molecular fingerprints) to predict hERG cardiotoxicity of compounds. 203 compounds with hERG inhibitory activity (pIC50) were retrieved from a previous study and predicting models were established using four machine learning algorithms based on the single and multi-dimensional molecular fingerprints. Results showed that MDFP has the potential to be an alternative to traditional molecular fingerprints and the combination of MDFP and traditional molecular fingerprints can achieve higher prediction accuracy. Meanwhile, the accuracy of the best model, which was generated by consensus of four algorithms with multi-dimensional molecular fingerprints, was 0.694 (RMSE) in the test dataset. Besides, the number of hydrogen bonds from MDFP has been determined as a critical factor in the predicting models, followed by rgyr and sasa. Our findings provide a new sight of MDFP and multi-dimensional molecular fingerprints in building models of hERG cardiotoxicity prediction.

pharmacology and toxicology↗