Biology subjects

Kang, K.

Publications and source records attributed to Kang, K..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Drosophila HCN mediates gustatory homeostasis by preserving sensillar transepithelial potential in sweet environments

Establishing transepithelial ion disparities is crucial for sensory functions in animals. In insect sensory organs called sensilla, a transepithelial potential, known as the sensillum potential (SP), arises through active ion transport across accessory cells, sensitizing receptor neurons such as mechanoreceptors and chemoreceptors. Because multiple receptor neurons are often co-housed in a sensillum and share SP, niche-prevalent overstimulation of single sensory neurons can compromise neighboring receptors by depleting SP. However, how such potential depletion is prevented to maintain sensory homeostasis remains unknown. Here, we find that the Ih-encoded hyperpolarization-activated cyclic nucleotide gated (HCN) channel bolsters the activity of bitter-sensing gustatory receptor neurons (bGRNs), albeit acting in sweet-sensing GRNs (sGRNs). For this task, HCN maintains SP despite prolonged sGRN stimulation induced by the diet mimicking their sweet feeding niche, such as overripe fruit. We present evidence that Ih-dependent demarcation of sGRN excitability is implemented to throttle SP consumption, which may have facilitated adaptation to a sweetness-dominated environment. Thus, HCN expressed in sGRNs serves as a key component of a simple yet versatile peripheral coding that regulates bitterness for optimal food intake in two contrasting ways: sweet-resilient preservation of bitter aversion and the previously reported sweet-dependent suppression of bitter taste.

neuroscience↗

bioRxiv2023

Evaluation of resampling-based inference for topological features of neuroimages

Many recent studies have demonstrated the inflated type 1 error rate of the original Gaussian random field (GRF) methods for inference of neuroimages and identified resampling (permutation and bootstrapping) methods that have better performance. There has been no evaluation of resampling procedures when using robust (sandwich) statistical images with different topological features (TF) used for neuroimaging inference. Here, we consider estimation of distributions TFs of a statistical image and evaluate resampling procedures that can be used when exchangeability is violated. We compare the methods using realistic simulations and study sex differences in life-span age-related changes in gray matter volume in the Nathan Kline Institute Rockland sample. We find that our proposed wild bootstrap and the commonly used permutation procedure perform well in sample sizes above 50 under realistic simulations with heteroskedasticity. The Rademacher wild bootstrap has fewer assumptions than the permutation and performs similarly in samples of 100 or more, so is valid in a broader range of conditions. We also evaluate the GRF-based pTFCE method and show that it has inflated error rates in samples less than 200. Our R package, pbj, is available on Github and allows the user to reproducibly implement various resampling-based group level neuroimage analyses.

neuroscience↗

bioRxiv2023

Caspase-1 activates gasdermin A in all non-mammals

Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis of the gasdermin family. A gene duplication of GSDMA in the common ancestor of caecilian amphibians, reptiles and birds gave rise to GSDMA-D in mammals. Uniquely in our tree, amphibian, reptile and bird GSDMA group in a separate clade than mammal GSDMA. Remarkably, GSDMA in numerous bird species contain caspase-1 cleavage sites like YVAD or FASD in the linker. We show that GSDMA from birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with the GSDMD C-terminal domain to confer the specificity of this interaction, whereas we show that bird caspase-1 uses a stereotypical tetrapeptide sequence to confer specificity for bird GSDMA. Our results reveal an evolutionarily stable association between caspase-1 and the gasdermin family, albeit a shifting one. Caspase-1 repeatedly changes its target gasdermin over evolutionary time at speciation junctures, initially cleaving GSDME in fish, then GSDMA in amphibians/reptiles/birds, and finally GSDMD in mammals. One Sentence SummaryWe demonstrate that amphibians, reptiles and birds engage pyroptosis using caspase-1 and GS-DMA, filling an evolutionary gap in which caspase-1 cleaves GSDME in fish and GSDMD in mammals.

immunology↗

bioRxiv2023

Unilateral ephaptic program underlying sweetness dominance

In ephaptic coupling, physically adjacent neurons influence one anothers activity via the electric fields they generate. To date, the molecular mechanisms that mediate and modulate ephaptic couplings effects remain poorly understood. Here, we show that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel lateralizes the potentially mutual ephaptic inhibition between Drosophila gustatory receptor neurons (GRNs). While sweet-sensing GRNs (sGRNs) engage in ephaptic suppression of the adjacent bitter-sensing GRNs (bGRNs), HCN expression in sGRNs enables them to resist ephaptic suppression from the bGRNs. Such one-sided ephaptic inhibition confers sweetness dominance, facilitating ingestion of bitter-laced sweets. Flies with HCN-deficient sGRNs exhibited dramatically decreased attraction to sucrose mixed with moderate levels of caffeine, highlighting the behavioral significance that gustatory ephaptic inhibition promotes ingestion of carbohydrates buried in bitterness. Our findings indicate a role for the gating of ephaptic coding to ensure the intake of the essential nutrient despite bitter contaminants present in the feeding niche of Drosophila, as the gating establishes a hierarchy of gustatory neuron excitation. Such refinement provides a previously unappreciated mechanism for controlling the activity of a neuronal network with potential implications in the mammalian brain, given the evolutionary conservation of the HCN genes.

neuroscience↗

bioRxiv2023

Study design features that improve effect sizes in cross-sectional and longitudinal brain-wide association studies

Brain-wide association studies (BWAS) are a fundamental tool in discovering brain-behavior associations. Several recent studies showed that thousands of study participants are required for good replicability of BWAS because the standardized effect sizes (ESs) are much smaller than the reported standardized ESs in smaller studies. Here, we perform analyses and meta-analyses of a robust effect size index using 63 longitudinal and cross-sectional magnetic resonance imaging studies from the Lifespan Brain Chart Consortium (77,695 total scans) to demonstrate that optimizing study design is critical for increasing standardized ESs and replicability in BWAS. A meta-analysis of brain volume associations with age indicates that BWAS with larger variability in covariate have larger reported standardized ES. In addition, the longitudinal studies we examined reported systematically larger standardized ES than cross-sectional studies. Analyzing age effects on global and regional brain measures from the United Kingdom Biobank and the Alzheimers Disease Neuroimaging Initiative, we show that modifying longitudinal study design through sampling schemes improves the standardized ESs and replicability. Sampling schemes that improve standardized ESs and replicability include increasing between-subject age variability in the sample and adding a single additional longitudinal measurement per subject. To ensure that our results are generalizable, we further evaluate these longitudinal sampling schemes on cognitive, psychopathology, and demographic associations with structural and functional brain outcome measures in the Adolescent Brain and Cognitive Development dataset. We demonstrate that commonly used longitudinal models can, counterintuitively, reduce standardized ESs and replicability. The benefit of conducting longitudinal studies depends on the strengths of the between-versus within-subject associations of the brain and non-brain measures. Explicitly modeling between-versus within-subject effects avoids averaging the effects and allows optimizing the standardized ESs for each separately. Together, these results provide guidance for study designs that improve the replicability of BWAS.

neuroscience↗

bioRxiv2022

Hierarchical cell-type identifier accurately distinguishes immune-cell subtypes enabling precise profiling of tissue microenvironment with single-cell RNA-sequencing

AO_SCPLOWBSTRACTC_SCPLOWSingle-cell RNA-seq enabled in-depth study on tissue micro-environment and immune-profiling, where a crucial step is to annotate cell identity. Immune cells play key roles in many diseases while their activities are hard to track due to diverse and highly variable nature. Existing cell-type identifiers had limited performance for this purpose. We present HiCAT, a hierarchical, marker-based cell-type identifier utilizing gene set analysis for statistical scoring for given markers. It features successive identification of major-type, minor-type and subsets utilizing subset markers structured in a three-level taxonomy tree. Comparison with manual annotation and pairwise match test showed HiCAT outperforms others in major- and minor-type identification. For subsets, we qualitatively evaluated marker expression profile demonstrating that HiCAT provide most clear immune cell landscape. HiCAT was also used for immune cell profiling in ulcerative colitis and discovered distinct features of the disease in macrophage and T cell subsets that could not be identified previously.

bioinformatics↗

bioRxiv2022

Integrative mapping of the dog epigenome: reference annotation for comparative inter-tissue and cross-species studies

The domestic dog has become a valuable model in exploring multifaceted diseases and biology important for human health. Large-scale dog genome projects produced high-quality draft references but still lack comprehensive annotation of encoded functional elements. Through the integrative next generation sequencing of transcriptomes paired with histone marks and DNA methylome profiling of 11 adult tissue types, implemented in a cross-species approach, we generated a reference epigenome of a domesticated dog. Using genome orthologues and synthenies, we deciphered the dogs epigenetic code by defining distinct chromatin states, allowing for genome-wide, integratable data production. We then characterized somatic super-enhancer landscapes and showed that genes mapped on these regions are associated with a broad range of biological and disease traits and are traceable to their tissue-of-origin. Ultimately, we delineated conserved epigenomic changes at the tissue- and species-specific resolutions. Our study provides an epigenomic blueprint of the dog for comparative biology and medical research.

genomics↗

bioRxiv2022

Emergence of hyper insecticide-resistant dengue vectors in Indochina Peninsula: threats of concomitant knockdown resistance mutations

Aedes aegypti (Linnaeus, 1762) is the main mosquito vector for dengue and other arboviral infectious diseases. Control of this important vector highly relies on the use of insecticides, especially pyrethroids. Nevertheless, the development of pyrethroid resistance is a major obstacle to mosquito/disease control worldwide. Here, we focused on the mutations in the target site of pyrethroid insecticides, voltage-sensitive sodium channel (Vssc), and found that Ae. aegypti collected from Vietnam has the L982W allele in the Vssc at a high frequency (>79%). L982W mutation is located in the highly conserved region of Vssc that is associated with sodium-ion selectivity and permeation rate. Strains having the L982W allele showed similar or even higher levels of resistance to pyrethroids than those having V1016G, a typical knockdown resistance allele in Asia. Furthermore, concomitant mutations L982W+F1534C and V1016G+F1534C were confirmed, and strains having these multiple Vssc mutations exhibited incomparably higher levels of pyrethroid resistance than any other field population ever reported. Molecular modeling analysis confirmed that these concomitant mutant alleles could interfere with approaching pyrethroid to Vssc. Remarkably, >90% of Vssc of Ae. aegypti were occupied by these hyper insecticide-resistant haplotypes in Phnom Penh city, Cambodia. Analysis of whole Vssc coding genes suggested that Vsscs have evolved into stronger resistant forms efficiently through gene recombination events. At this point, L982W has never been detected in Vssc of Ae. aegypti from any other neighboring countries. We strongly emphasize the need to be vigilant about these strong resistance genes spreading to the world through Indochina Peninsula. Significance StatementThe high frequency (>78%) of the L982W allele was detected at the target site of the pyrethroid insecticide, the voltage-sensitive sodium channel (Vssc) of Aedes aegypti collected from Vietnam and Cambodia. Haplotypes having concomitant mutations L982W+F1534C and V1016G+F1534C were also confirmed in both countries, and their frequency was high (>90%) in Phnom Penh, Cambodia. Strains having these haplotypes exhibited substantially higher levels of pyrethroid resistance than any other field population ever reported. The L982W mutation has never been detected in any country of the Indochina Peninsula except Vietnam and Cambodia, but it may be spreading to other areas of Asia, which can cause an unprecedentedly serious threat to the control of dengue fever as well as other Aedes-borne infectious diseases.

neuroscience↗

bioRxiv2021

Oxalic acid binds to gustatory receptor Gr23a and inhibits feeding in the brown planthopper

Plants produce diverse secondary compounds as natural protection against microbial and insect attack. Most of these compounds, including bitters and acids, are sensed by insect gustatory receptors (Grs). Acids are potentially toxic to insects, but there are few reports on sour compounds as ligands of insect Grs. Here, using two different heterologous expression systems, the insect Sf9 cell line and the mammalian HEK293T cell line, we started from crude extracts of rice (Oryza sativa) and successfully identified oxalic acid (OA) as a ligand of NlGr23a, a Gr in the brown planthopper Nilaparvata lugens. The antifeedant effect of OA on the brown planthopper was dose dependent, and NlGr23a is essential for OAs antifeedant activity in both artificial diets and rice plants. NlGr23a is also indispensable for tarsal OA sensing. To our knowledge, OA is the first identified ligand starting from plant crude extracts and the first known strong acid for insect Grs. These findings on rice-planthopper interactions will be of broad interest for pest control in agriculture and also for better understanding of how insects select host plants. Research organismNilaparvata lugens

ecology↗

bioRxiv2021

Neuromuscular connectomes across development reveal synaptic ordering rules

In mammals, the connections between motor neurons and muscle fibers profoundly reorganize in the early postnatal period. To better understand this synaptic rewiring we traced out all the connectivity in muscles at successive ages in the mouse using serial section scanning electron microscopy in a muscle at birth and Brainbow-based and XFP-based fluorescent reconstructions in neonatal and older muscles respectively. Our data indicate that axons prune about 85% of their branches in the first two weeks of postnatal life, and that while much of this pruning leaves neuromuscular junctions with only one remaining axon (a [~]8-fold reduction), it also causes a [~]6-fold reduction in the number of muscle fibers that possess more than one neuromuscular junction. Unexpectedly, the simplification of the wiring diagram was not haphazard but rather was constrained by the tendency for neurons to maintain co-innervation the longest with other neurons based on their proximity in an abstract rank order. This synaptic ordering preference was even significant at birth when connectivity was the most overlapping but became more striking as development proceeded and was even obvious in the few adult muscle fibers that retained more than one axon at different neuromuscular junctions. Analysis of properties of muscle fibers sharing axons at developing ages and changes in the physical distance between neuromuscular junctions that were maintained in young versus older muscles suggests that the rank order of motor neurons is based on their relative similarity in activity patterns. This same ranking governs both the close-proximity synaptic competitions within neuromuscular junctions and the long-distance competitions that remove or maintain synapses millimeters apart meaning that all neuromuscular rewiring is based on the same global activity ordering rule. We think it is likely that this ranking is related to the ultimate recruitment order of motor axon activity as first described by (Henneman, 1957). Thus the emerging structure of neuromuscular circuitry is a product of its function: initial nearly all-to-all connectivity gives rise to a well-organized system of axons, allowing for the orderly recruitment of neurons during a smoothly graded behavior.

neuroscience↗

bioRxiv2021

Voxelated Bioprinting of Mechanically Robust Multiscale Porous Scaffolds for Pancreatic Islets

Three-dimensional (3D) bioprinting additively assembles bio-inks to manufacture tissue-mimicking biological constructs, but with the typical building blocks limited to one-dimensional filaments. Here, we develop a technique for the digital assembly of spherical particles (DASP), which are effectively zero-dimensional voxels - the basic unit of 3D structures. We show that DASP enables on-demand generation, deposition, and assembly of viscoelastic bio-ink droplets. We establish a phase diagram that outlines the viscoelasticity of bio-inks required for printing spherical particles of good fidelity. Moreover, we develop a strategy for engineering bio-inks with independently controllable viscoelasticity and mesh size. Using DASP, we create mechanically robust, multiscale porous scaffolds composed of interconnected yet distinguishable hydrogel particles. Finally, we demonstrate the application of the scaffolds in encapsulating human pancreatic islets for responsive insulin release. Together with the knowledge of bio-ink design, DASP might be used to engineer highly heterogeneous yet tightly organized tissue constructs for therapeutic applications. Table of ContentsA three-dimensional bioprinting technology is developed to enable on-demand generation, deposition, and assembly of viscoelastic bio-ink droplets in a biofriendly environment. A strategy is developed to independently control elasticity, viscosity, and mesh size of bio-inks. The technique allows for easy manufacturing mechanically robust multiscale porous scaffolds, which can be used to encapsulate human pancreatic islets for sustained responsive insulin release. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/449587v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@1c0f2eaorg.highwire.dtl.DTLVardef@8bf924org.highwire.dtl.DTLVardef@191bd3aorg.highwire.dtl.DTLVardef@11e5ce1_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2021

Enhancer RNAs stimulate Pol II pause release by harnessing multivalent interactions to NELF

Enhancer RNAs (eRNAs) are long non-coding RNAs that originate from enhancers. Although eRNA transcription is a canonical feature of activated enhancers, the molecular features required for eRNA function and the mechanism of how eRNAs impinge on target gene transcription have not been established. Thus, using eRNA-dependent RNA polymerase II (Pol II) pause release as a model, we examined the requirement of sequence, structure and length of eRNAs for their ability to stimulate Pol II pause release by detaching NELF from paused Pol II. We found eRNA not to exert their function through common structural or sequence motifs. Instead, efficient NELF release requires a single eRNA molecule that must contain unpaired guanosines to make multiple, allosteric contacts with several NELF subunits. By revealing the molecular determinants for eRNA function, our study mechanistically links eRNAs to Pol II pause release and provides new insight into the regulation of metazoan transcription.

biochemistry↗

bioRxiv2021

Strain dynamics of specific contaminant bacteria modulate the performance of ethanol biorefineries

Bioethanol is a viable alternative for fossil fuels, and its use has lowered CO2 emissions by over 500 million tonnes in Brazil alone by replacing more than 40% of the national gasoline consumption. However, contaminant bacteria reduce yields during fermentation. Our understanding of these contaminants is limited to targeted studies, and the interplay of the microbial community and its impact on fermentation efficiency remains poorly understood. Comprehensive surveying and longitudinal analysis using shotgun metagenomics of two major biorefineries over a production season revealed similar patterns in microbial community structure and dynamics throughout the entire fermentation system. Strain resolution metagenomics identified specific Lactobacillus fermentum strains as strongly associated with poor industrial performance and laboratory-scale fermentations revealed yield reductions of up to 4.63{+/-}1.35% depending on the specific contaminating strains. Selective removal of these strains could reduce emissions from the bioethanol industry by more than 2x106 tonnes per year. Using the large-scale Brazilian ethanol fermentations as a model system for studying microbiome-phenotype relationships this study further demonstrates how high-resolution metagenomics can identify culprits of large scale industrial biomanufacturing.

microbiology↗

bioRxiv2021

CDSeqR: fast complete deconvolution for gene expression data from bulk tissues

BackgroundBiological tissues consist of heterogenous populations of cells. Because gene expression patterns from bulk tissue samples reflect the contributions from all cells in the tissue, understanding the contribution of individual cell types to the overall gene expression in the tissue is fundamentally important. We recently developed a computational method, CDSeq, that can simultaneously estimate both sample-specific cell-type proportions and cell-type-specific gene expression profiles using only bulk RNA-Seq counts from multiple samples. Here we present an R implementation of CDSeq (CDSeqR) with significant performance improvement over the original implementation in MATLAB and an added new function to aid cell type annotation. The R package would be of interest for the broader R community. ResultWe developed a novel strategy to substantially improve computational efficiency in both speed and memory usage. In addition, we designed and implemented a new function for annotating the CDSeq estimated cell types using single-cell RNA sequencing (scRNA-seq) data. This function allows users to readily interpret and visualize the CDSeq estimated cell types. In addition, this new function further allows the users to annotate CDSeq-estimated cell types using marker genes. We carried out additional validations of the CDSeqR software using synthetic, real cell mixtures, and real bulk RNA-seq data from the Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) project. ConclusionsThe existing bulk RNA-seq repositories, such as TCGA and GTEx, provide enormous resources for better understanding changes in transcriptomics and human diseases. They are also potentially useful for studying cell-cell interactions in the tissue microenvironment. Bulk level analyses neglect tissue heterogeneity, however, and hinder investigation of a cell-type-specific expression. The CDSeqR package may aid in silico dissection of bulk expression data, enabling researchers to recover cell-type-specific information.

bioinformatics↗

bioRxiv2021

Arsenic hexoxide has differential effects on cell proliferation and genome-wide gene expression in human primary mammary epithelial and MCF7 cells

Arsenic is reportedly a biphasic inorganic compound for its toxicity and anticancer effects in humans [1, 2]. Recent studies have shown that certain arsenic compounds including arsenic hexoxide (AS4O6; hereafter, AS6) induce programmed cell death and cell cycle arrest in human cancer cells and murine cancer models [3, 4]. However, the mechanisms by which AS6 suppresses cancer cells are incompletely understood. In this study, we report the mechanisms of AS6 through transcriptome analyses. In particular, the cytotoxicity and global gene expression regulation by AS6 were compared in human normal and cancer breast epithelial cells. Using RNA-sequencing and bioinformatics analyses, differentially expressed genes in significantly affected biological pathways in these cell types were validated by real-time quantitative polymerase chain reaction and immunoblotting assays. Our data show markedly differential effects of AS6 on cytotoxicity and gene expression in human mammary epithelial normal cells (HUMEC) and Michigan Cancer Foundation 7 (MCF7), a human mammary epithelial cancer cell line. AS6 selectively arrests cell growth and induces cell death in MCF7 cells without affecting the growth of HUMEC in a dose-dependent manner. AS6 alters the transcription of a large number of genes in MCF7 cells, but much fewer genes in HUMEC. Importantly, we found that the cell proliferation, cell cycle, and DNA repair pathways are significantly suppressed whereas cellular stress response and apoptotic pathways increase in AS6-treated MCF7 cells. Together, we provide the first evidence of differential effects of AS6 on normal and cancerous breast epithelial cells, suggesting that AS6 at moderate concentrations induces cell cycle arrest and apoptosis through modulating genome-wide gene expression, leading to compromised DNA repair and increased genome instability selectively in human breast cancer cells.

genetics↗

bioRxiv2020

BRCA1-BARD1 regulates transcription through modulating topoisomerase IIβ

RNA polymerase II (Pol II)-dependent transcription in stimulus-inducible genes requires topoisomerase II{beta} (TOP2B)-mediated DNA strand break and the activation of DNA damage response signaling in humans. Here, we report a novel function of the breast cancer 1 (BRCA1)-BRCA1 associated ring domain 1 (BARD1) complex, in this process. We found that BRCA1 is phosphorylated at S1524 by the kinases ATM and ATR during gene activation and that this event is essential for productive transcription. Our in vitro biochemical analyses showed TOP2B and BARD1 interaction and colocalization in the EGR1 transcription start site (TSS) and that the BRCA1-BARD1 complex ubiquitinates TOP2B, which appears to stabilize TOP2B protein in the cell and binding to DNA. Intriguingly, BRCA1 phosphorylation at S1524 controls this interaction. In addition, genomic analyses indicated colocalization between TOP2B and BRCA1 in a large number of protein-coding genes. Together, these findings reveal the novel function of the BRCA1-BARD1 complex in gene expression and in the regulation of TOP2B during Pol II transcription. Significance StatementMaintaining genomic integrity against cellular and extracellular genotoxic elements is essential for normal cell growth and function. Recent studies indicated that stimulus-induced transcription provokes topoisomerase II{beta}-mediated DNA strand break and DNA damage response signaling, requiring DNA repair to be coupled with transcription. Here, we present a novel role for the BRCA1-BARD1 complex in regulating the transcription of serum-inducible genes and the stability of topoisomerase II{beta}. The mechanism involving topoisomerase II{beta} ubiquitination by the BRCA1-BARD1 complex and the phosphorylation of BRCA1 S1524 upon transcriptional activation appears to function as a switch to the reaction. Our findings provide the first evidence of functional interaction between the BRCA1-BARD1 complex and topoisomerase II{beta} in transcription in humans.

molecular biology↗

bioRxiv2020

Meta-Prism 2.0: Enabling algorithm for ultra-fast, accurate and memory-efficient search among millions of microbial community samples

MotivationMicrobial community samples and sequencing data have been accumulated at a speed faster than ever, with tens of thousands of samples been sequenced each year. Mining such a huge amount of multi-source heterogeneous data is becoming more and more difficult. Among several sample mining bottlenecks, efficient and accurate search of samples is one of the most prominent: Faced with millions of samples in the data repository, traditional sample comparison and search approaches fall short in speed and accuracy. ResultsHere we proposed Meta-Prism 2.0, a microbial community sample search method based on smart pair-wise sample comparison, which pushed the time and memory efficiency to a new limit, without the compromise of accuracy. Based on memory-saving data structure, time-saving instruction pipeline, and boost scheme optimization, Meta-Prism 2.0 has enabled ultra-fast, accurate and memory-efficient search among millions of samples. Meta-Prism 2.0 has been put to test on several datasets, with largest containing one million samples. Results have shown that firstly, as a distance-based method, Meta-Prism 2.0 is not only faster than other distance-based methods, but also faster than unsupervised methods. Its 0.00001s per sample pair search speed, as well as 8GB memory needs for searching against one million samples, have enabled it to be the most efficient method for sample comparison. Additionally, Meta-Prism 2.0 could achieve the comparison accuracy and search precision that are comparable or better than other contemporary methods. Thirdly, Meta-Prism 2.0 can precisely identify the original biome for samples, thus enabling sample source tracking. ConclusionIn summary, Meta-Prism 2.0 can perform accurate searches among millions of samples with very low memory cost and fast speed, enabling knowledge discovery from samples at a massive scale. It has changed the traditional resource-intensive sample comparison and search scheme to a cheap and effective procedure, which could be conducted by researchers everyday even on a laptop, for insightful sample search and knowledge discovery. Meta-Prism 2.0 could be accessed at: https://github.com/HUST-NingKang-Lab/Meta-Prism-2.0.

bioinformatics↗

bioRxiv2020

Ontology-Aware Deep Learning Enables Ultrafast, Accurate and Interpretable Source Tracking among Sub-Million Microbial Community Samples from Hundreds of Niches

The taxonomical structure of microbial community sample is highly habitat-specific, making it possible for source tracking niches where samples are originated. Current methods face challenges when the number of samples and niches are magnitudes more than current in use, under which circumstances they are unable to accurately source track samples in a timely manner, rendering them difficult in knowledge discovery from sub-million heterogeneous samples. Here, we introduce a deep learning method based on Ontology-aware Neural Network approach, ONN4MST (https://github.com/HUST-NingKang-Lab/ONN4MST), which takes into consideration the ontology structure of niches and the relationship of samples from these ontologically-organized niches. ONN4MSTs superiority in accuracy, speed and robustness have been proven, for example with an accuracy of 0.99 and AUC of 0.97 in a microbial source tracking experiment that 125,823 samples and 114 niches were involved. Moreover, ONN4MST has been utilized on several source tracking applications, showing that it could provide highly-interpretable results from samples with previously less-studied niches, detect microbial contaminants, and identify similar samples from ontologically-remote niches, with high fidelity.

bioinformatics↗