Biology subjects

Song, C.

Publications and source records attributed to Song, C..

At least 127 records · Page 7Linked to original sources

bioRxiv2022

Characterization and identification of a novel daidzein reductase involved in (S)-equol biosynthesis in Clostridium C1

(S)-equol is an isoflavone with high estrogen-like activity and no toxic effects in the human body, and is only produced by some gut bacteria in vivo. It plays an important role in maintaining individual health, however, the dearth of resources associated with (S)-equol-producing bacteria has seriously restricted the production and application of (S)-equol. We report here a novel functional gene C1-07020 that was identified from a chick (S)-equol-producing bacterium (Clostridium C1). We found that recombinant protein of C1-07020 possessed similar function to daidzein reductase (DZNR), which can convert daidzein (DZN) into R/S-dihydrodaidzein (R/S-DHD). Interestingly, C1-07020 can reverse convert (R/S)-DHD (DHD oxidases) into DZN even without cofactors or anaerobic conditions. Additionally, high concentrations of (S)-equol can directly promote DHD oxidase but inhibit DZNR activity. Molecular docking and site-directed mutagenesis revealed that the amino acid Arg 75 was the active site of DHD oxidases. Subsequently, an engineered E. coli strain based on C1-07020 was constructed and showed higher yield of (S)-equol than the engineered bacteria from our previous work. Metagenomics analysis and PCR detection surprisingly revealed that C1-07020 and related bacteria may be prevalent in the gut of humans and animals and their (S)-equol production state may cause differed between (S)-equol producer and non-producer. Overall, a novel DZNR from Clostridium C1 was found and identified in this study, and its bidirectional enzyme activities and wide distribution in the gut of humans and animals provide alternative strategies for revealing the individual regulatory mechanisms of (S)-equol-producing bacteria. Importance(S)-equol is a final product of DZN that metabolized by some enteric bacteria. Although (S)-equol played very important roles in maintaining human health, larger differences in equol production varied between different populations. Here, a novel DZNR gene C1-07020, which related to (S)-equol production, was reported. The bidirectional enzyme functions and wide distribution of C1-07020 in human and animal gut provided additional insights into the metabolic regulation of (S)-equol. Additionally, C1-07020 can be used for improving the production of (S)-equol in vitro.

microbiology↗

bioRxiv2021

Along the Bos Taurus genome, uncover candidate Imprinting Control Regions

In mammals, Imprinting Control Regions (ICRs) regulate a subset of genes in a parent-of-origin-specific manner. In both human and mouse, previous studies identified a set of CpG-rich motifs that occurred as clusters in ICRs and germline Differentially Methylated Regions (gDMRs). These motifs consist of the ZFP57 binding site (ZFBS) overlapping a subset of MLL binding units known as MLL morphemes. Furthermore, by creating plots for displaying the density of these overlaps, it became possible to locate known and candidate ICRs in mouse and human genomic DNA. Since genomic imprinting impacts many developmental and key physiological processes, we performed genome-wide analyses to create plots displaying the density of the CpG-rich motifs (ZFBS-morph overlaps) along Bos Taurus chromosomal DNA. We tailored our datasets so that they could be displayed on the UCSC genome browser (the build bosTau8). On the genome browser, we could view the ZFP57 binding sites, the ZFBS-morph overlaps, and peaks in the density-plots in the context of cattle RefSeq Genes, Non-Cow RefSeq Genes, CpG islands, and Single nucleotide polymorphisms (SNPs). Our datasets revealed the correspondence of peaks in plots to known and deduced ICRs in Bos Taurus genomic DNA. We illustrate that by uploading our datasets onto the UCSC genome browser, we could discover candidate ICRs in cattle DNA. In enlarged views, we could pinpoint the genes in the vicinity of candidate ICRs and thus discover potential imprinted genes.

genomics↗

bioRxiv2021

A magnetic field prevents alcoholic liver disease by reducing oxidative stress

The radical-pair recombination change will affect the generation of free radicals, which can be regulated by static magnetic fields (SMFs) in a SMF setting dependent way. It is well known that alcohol consumption leads to significantly increased free radical levels and health risks, which lacks effective treatment method besides alcohol abstinence. Here we compared different SMF settings and found that a downward SMF of [~]0.1 T with magnetic flux of [~]4.5x10-3 Wb could effectively alleviate alcohol-induced liver damage and lipid accumulation, and improve liver function. The inflammation, reactive oxygen species (ROS) level and oxidative stress were significantly reduced. EPR (electron paramagnetic resonance) experiments also confirmed the reduced amount of free radical by SMF treatment. Moreover, the lifespan of heavy alcohol drinking mice was also significantly changed due to the SMF effects on liver cell ROS level, DNA synthesis and liver cell regeneration. Our study shows that moderate SMFs with specific parameters have great promises to be developed into a physical method to reduce alcohol-induced liver damage in the future.

physiology↗

bioRxiv2021

A multi-class gene classifier for SARS-CoV-2 variants based on convolutional neural network

Surveillance of circulating variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of great importance in controlling the coronavirus disease 2019 (COVID-19) pandemic. We propose an alignment-free in silico approach for classifying SARS-CoV-2 variants based on their genomic sequences. A deep learning model was constructed utilizing a stacked 1-D convolutional neural network and multilayer perceptron (MLP). The pre-processed genomic sequencing data of the four SARS-CoV-2 variants were first fed to three stacked convolution-pooling nets to extract local linkage patterns in the sequences. Then a 2-layer MLP was used to compute the correlations between the input and output. Finally, a logistic regression model transformed the output and returned the probability values. Learning curves and stratified 10-fold cross-validation showed that the proposed classifier enables robust variant classification. External validation of the classifier showed an accuracy of 0.9962, precision of 0.9963, recall of 0.9963 and F1 score of 0.9962, outperforming other machine learning methods, including logistic regression, K-nearest neighbor, support vector machine, and random forest. By comparing our model with an MLP model without the convolution-pooling network, we demonstrate the essential role of convolution in extracting viral variant features. Thus, our results indicate that the proposed convolution-based multi-class gene classifier is efficient for the variant classification of SARS-CoV-2.

bioinformatics↗

bioRxiv2021

Particle morphology of medusavirus inside and outside the cells reveals a new maturation process of giant viruses

Medusavirus, a giant virus, is phylogenetically closer to eukaryotes than the other giant viruses and has been recently classified as an independent species. However, details of its morphology and maturation process in host cells remain unclear. Here, we investigated the particle morphology of medusavirus inside and outside infected cells using conventional transmission electron microscopy (C-TEM) and cryo-electron microscopy (cryo-EM). The C-TEM of amoeba infected with the medusavirus showed four types of particles: empty, DNA-full, and the corresponding intermediates. Time-dependent changes in the proportion and following intracellular localization of these particles suggested a new maturation process for the medusavirus. Empty particles and viral DNAs were produced independently in the cytoplasm and nucleus, respectively, and only empty particles located near the nucleus incorporated the viral DNA into the capsid. All four types of particles were also found outside the cells. The cryo-EM of these particles showed that the intact capsid structure, covered with three different types of spikes, was conserved among all particle types, although with minor size-related differences. The internal membrane exhibited a structural array similar to that of the capsid, interacted closely with the capsid, and displayed open membrane structures in the empty and empty-intermediate particles. This result suggests that the open structures in the internal membrane are used for an exchange of scaffold proteins and viral DNA during the maturation process. This new model of the maturation process of medusavirus provides insight into the structural and behavioral diversity of giant viruses. ImportanceGiant viruses exhibit diverse morphologies and maturation processes. In the present study, medusavirus showed four types of particle morphologies both inside and outside the infected cells, when propagated in the laboratory using amoeba culture. Time-course analysis of the medusavirus particles in the infected cells reveals a new maturation process. Empty viral particles and viral DNAs were produced independently in the cytoplasm and nucleus, and only the empty particles located near the nucleus incorporated the viral DNA. Consequently, many immature particles, along with mature virions, were released from the host cells. Except for showing a small change in size, the capsid structures were well preserved during the maturation process. The empty viral particles and corresponding intermediates showed open membrane structures, which are presumably used for exchanging scaffold proteins and viral DNAs.

microbiology↗

bioRxiv2021

ASF1 activation PI3K/AKT pathway regulates sexual and asexual development in filamentous ascomycete

Sexual and asexual reproduction is ubiquitous in eukaryotes. PI3K/AKT signaling pathway can modulate sexual reproduction in mammals. However, this signaling pathway modulating sexual and asexual reproduction in fungi is scarcely understood. SeASF1, a SeH4 chaperone, could manipulate sexual and asexual reproduction of Stemphylium eturmiunum. SeDJ-1, screened from Se{Delta}asf1 transcriptome, was confirmed to regulate sexual and asexual development by RNAi, of which the mechanism was demonstrated by detecting transcriptional levels and protein interactions of SeASF1, SeH4 and SeDJ-1 by qRT-PCR, and Y2H, Co-IP and Pull-down, respectively. SeASF1 coupling SeH4 bound SeDJ-1 to arouse the sexual and asexual activity. In S. eturmiunum genome, SeDJ-1 was upstream while SeGSK3 was downstream in PI3K/AKT signaling pathway. Moreover, SeDJ-1 interacted with SePI3K or SeGSK3 in vivo and in vitro. Significantly, SeDJ-1 or SePI3K could effectively stimulate sexual activity alone, but SePI3K could recover the sexual development of SiSeDJ-1. Meanwhile, SeDJ-1-M6 was a critical segment for interaction of SeDJ-1 with SePI3K. SeDJ-1-M6 played a critical role in irritating sexual reproduction in SiSePI3K, which further uncovered the regulated mechanism of SeDJ-1. Summarily, SeASF1 coupling SeH4 motivates SeDJ-1 to arouse SePI3K involved in sexual reproduction. Thus, SeASF1 can activate PI3K/AKT signaling pathway to regulate sexual and asexual development in filamentous ascomycete.

microbiology↗

bioRxiv2021

Sucrose-dependence of sugar uptake, quorum sensing and virulence of the rice blight pathogen Xanthomonas oryzae pv. oryzae

Withdrawal StatementThe authors have withdrawn their manuscript owing to potential issues with the qRT-PCR data and issues with accessing some of the raw data from one of the authors (FAIR principle requirements). Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

plant biology↗

bioRxiv2021

Proteome-wide screening for mitogen-activated protein kinase docking motifs and interactors

Essential functions of mitogen-activated protein kinases (MAPKs) depend on their capacity to selectively phosphorylate a limited repertoire of substrates. MAPKs harbor a conserved groove located outside of the catalytic cleft that binds to short linear sequence motifs found in substrates and regulators. However, the weak and transient nature of these "docking" interactions poses a challenge to defining MAPK interactomes and associated sequence motifs. Here, we describe a yeast-based genetic screening pipeline to evaluate large collections of MAPK docking sequences in parallel. Using this platform we analyzed a combinatorial library based on the docking sequences from the MAPK kinases MKK6 and MKK7, defining features critical for binding to the stress-activated MAPKs JNK1 and p38. We subsequently screened a library consisting of ~12,000 sequences from the human proteome, revealing a large number of MAPK-selective interactors, including many not conforming to previously defined docking motifs. Analysis of p38/JNK1 exchange mutants identified specific docking groove residues mediating selective binding. Finally, we verified that docking sequences identified in the screen could function in substrate recruitment in vitro and in cultured cells. Collectively, these studies establish an approach for characterization of MAPK docking sequences and provide a resource for future investigation of signaling downstream of p38 and JNK MAP kinases.

cell biology↗

bioRxiv2021

Strigo-D2 - a bio-sensor for monitoring the spatio-temporal pattern of strigolactone signaling in intact plants

Strigolactones (SLs) are a class of plant hormones modulating developmental programs in response to endogenous and exogenous stimuli and mediating biotic interactions. However, a comprehensive view on the spatio-temporal pattern of SL signaling has not been established and tools for a systematic in planta analysis do not exist. Here, we present Strigo-D2, a genetically encoded ratiometric SL signaling sensor, allowing the examination of SL signaling distribution with cellular resolution and its rapid response to altered SL levels in intact plants. By monitoring the abundance of a truncated and fluorescently labeled SUPPRESSOR OF MAX2 1-LIKE 6 (SMXL6) protein, a proteolytic target of the SL signaling machinery, we show that all cell types investigated have the capacity to respond to changes in SL levels but with very different dynamics. In particular, SL signaling is pronounced in vascular cells but low in guard cells and the meristematic region of the root. We also show that other hormones leave Strigo-D2 activity unchanged indicating that initial SL signaling steps work in isolation from other hormonal signaling pathways. Specificity and spatio-temporal resolution of Strigo-D2 underline the value of the sensor for monitoring SL signaling in a broad range of biological contexts and with highly instructive analytical depth.

plant biology↗

bioRxiv2021

GSA: An Independent Development Algorithm for Calling Copy Number and Detecting Homologous Recombination Deficiency (HRD) from Target Capture Sequencing

BackgroundThe gain or loss of large chromosomal regions or even whole chromosomes is termed as genomic scarring and can be observed as copy number variations resulting from the failure of DNA damage repair. ResultsIn this study, a new algorithm called Genomic Scar Analysis (GSA) has developed and validated to calculate homologous recombination deficiency (HRD) score. The two critical submodules were tree recursion (TR) segmentation and filtering, and the estimation and correction of the tumor purity and ploidy. Then, this study evaluated the rationality of segmentation and genotype identification by the GSA algorithm and compared with other two algorithms, PureCN and ASCAT, found that the segmentation result of GSA algorithm was more logical. In addition, the results indicated that the GSA algorithm had an excellent predictive effect on tumor purity and ploidy, if the tumor purity was more than 20%. Furtherly, this study evaluated the HRD scores and BRCA1/2 deficiency status of 195 clinical samples, and the results indicated that the accuracy was 0.98 (comparing with Affymetrix OncoScan assay) and the sensitivity was 95.2% (comparing with BRCA1/2 deficiency status), both were well-behaved. Finally, HRD scores and 16 genes mutations (TP53 and 15 HRR pathway genes) were analyzed in 17 cell lines, the results showed that there was higher frequency in HRR pathway genes in high HRD score samples. ConclusionsThis new algorithm, named as GSA, could effectively and accurately calculate the purity and ploidy of tumor samples through NGS data, and then reflect the degree of genomic instability and large-scale copy number variations of tumor samples.

bioinformatics↗

bioRxiv2021

The impact of mutation L138F/L210F on the Orai channel: a molecular dynamics simulation study

The calcium release-activated calcium (CRAC) channel, composed of the Orai channel and the STIM protein, plays a crucial role in maintaining the Ca2+ concentration in cells. Previous studies showed that the L138F mutation in the human Orai1 creates a constitutively open channel independent of STIM, causing severe myopathy, but how the L138F mutation activates Orai1 is still unclear. Here, based on the crystal structure of Drosophila melanogaster Orai (dOrai), molecular dynamics simulations for the wild-type (WT) and the L210F (corresponding to L138F in the human Orai1) mutant were conducted to investigate their structural and dynamical properties. The results showed that the L210F dOrai mutant tends to have a more hydrated hydrophobic region (V174 to F171), as well as more dilated basic region (K163 to R155) and selectivity filter (E178). Sodium ions were located deeper in the mutant than in the WT. Further analysis revealed two local but essential conformational changes that may be the key to the activation. A rotation of F210, a previously undescribed feature, was found to result in the opening of the K163 gate through hydrophobic interactions. At the same time, a counter-clockwise rotation of F171 occurred more frequently in the mutant, resulting in a wider hydrophobic gate with more hydration. Ultimately, the opening of the two gates may facilitate the opening of the Orai channel independent of STIM.

biophysics↗

bioRxiv2021

Desiccation-induced fibrous condensation of CAHS protein from an anhydrobiotic tardigrade

Anhydrobiosis is one of the most extensively studied forms of cryptobiosis that is induced in certain organisms as a response to desiccation. Anhydrobiotic species has been hypothesized to produce substances that can protect their biological components and/or cell membranes without water. In extremotolerant tardigrades, highly hydrophilic and heat-soluble protein families, cytosolic abundant heat-soluble (CAHS) proteins, have been identified, which are postulated to be integral parts of the tardigrades response to desiccation. However, the molecular mechanisms underlying these protein functions remain to be fully elucidated. In this study, we perfomed in vitro and in vivo characterizations of the self-assembling property of CAHS1 protein, a major isoform of CAHS proteins from Ramazzottius varieornatus, using a series of spectroscopic and microscopic techniques. Our in vitro observations showed that CAHS1 proteins homo-oligomerized via the C-terminal -helical region and formed a hydrogel as their concentration increased, and that these molecular assembling processes were reversible. Furthermore, our in vivo observations demonstrated that the overexpressed CAHS1 proteins formed condensates under desiccation-mimicking conditions. These data strongly suggested that, upon drying, the CAHS1 proteins form oligomers and eventually underwent sol-gel transition in tardigrade cytosols. Thus, it is proposed that the CAHS1 proteins form the cytosolic fibrous condensates, which presumably have variable mechanisms for the desiccation tolerance of tardigrades. These findings provide insights into the protective mechanisms involved in the anhydrobiosis of tardigrades.

biochemistry↗

bioRxiv2021

Exosome component 1 cleaves single-stranded DNA and sensitizes kidney renal clear cell carcinoma cells to poly(ADP-ribose) polymerase inhibitor

Targeting DNA repair pathway offers an important therapeutic strategy for cancers. However, the failure of DNA repair inhibitors to markedly benefit patients necessitates the development of new strategies. Here, we show that exosome component 1 (EXOSC1) promotes DNA damages and sensitizes kidney renal clear cell carcinoma (KIRC) cells to DNA repair inhibitor. Considering that endogenous source of mutation (ESM) constantly assaults genomic DNA and likely sensitize cancer cells to the inhibitor, we first analyzed the statistical relationship between the expression of individual genes and the mutations for KIRC. Among the candidates, EXOSC1 most notably promoted DNA damages and subsequent mutations via preferentially cleaving C site(s) in single-stranded DNA. Consistently, EXOSC1 was more significantly correlated with C>A transversions in coding strands than these in template strands in KIRC. Notably, KIRC patients with high EXOSC1 showed a poor prognosis, and EXOSC1 sensitized cancer cells to poly(ADP-ribose) polymerase inhibitor. These results show that EXOSC1 acts as an ESM in KIRC, and targeting EXOSC1 might be a potential therapeutic strategy.

cancer biology↗

bioRxiv2021

Nasal delivery of single-domain antibodies improve symptoms of SARS-CoV-2 infection in an animal model

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed particularly for treating life-threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited SARS-CoV-2 titers in infected lungs of Syrian hamsters without causing weight loss and cytokine induction. In vitro studies demonstrated that K-874A neutralized SARS-CoV-2 in both VeroE6/TMPRSS2 and human lung-derived alveolar organoid cells. Unlike other drug candidates, K-874A blocks viral membrane fusion rather than viral attachment. Cryo-electron microscopy revealed K-874A bound between the receptor binding domain and N-terminal domain of the virus S protein. Further, infected cells treated with K-874A produced fewer virus progeny that were less infective. We propose that direct administration of K-874A to the lung via a nebulizer could be a new treatment for preventing the reinfection of amplified virus in COVID-19 patients. Author summaryVaccines for COVID-19 are now available but therapeutic drugs are still needed to treat life-threatening cases and those who cannot be vaccinated. We discovered a new heavy-chain single-domain antibody that can effectively neutralize the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19. Unlike other drug candidates, which prevent the virus from attaching to the receptor on the host cell, this new antibody acts by blocking the virus membrane from fusing with the host cell membrane. We studied the behavior of the new antibody in vitro using VeroE6/TMPRSS2 cells and human lung organoids. When delivered through the nose to infected Syrian hamsters, we found that this antibody could prevent the typical symptoms caused by SARS-CoV-2. Our results are significant because delivering simple drugs directly to infected lungs using a nebulizer could increase the potency of the drugs while reducing the risk of immune reaction that could occur if the drugs escape or are delivered through the blood stream.

microbiology↗

bioRxiv2021

Caspase-dependent cleavage of DDX21 suppresses host innate immunity

DEAD (Glu-Asp-Ala-Glu)-box RNA helicases have been proven to contribute to antiviral innate immunity. DDX21 RNA helicase was identified as a nuclear protein involved in ribosomal RNA processing and RNA unwinding. DDX21 was also proved to be the scaffold protein in the complex of DDX1-DDX21-DHX36 which senses double strand RNA and initiates downstream innate immunity. Here, we identified that DDX21 undergoes caspase-dependent cleavage after virus infection and treatment with RNA/DNA ligands, especially for RNA virus and ligands. Caspase-3/6 cleave DDX21 at D126 and promotes its translocation from the nucleus to the cytoplasm in response to virus infection. The cytoplasmic cleaved DDX21 negatively regulates the IFN-{beta} signaling pathway by suppressing the formation of DDX1-DDX21-DHX36 complex. Thus, our data identify DDX21 as a regulator of immune balance and most importantly uncover a potential role of DDX21 cleavage in the innate immunity response towards virus. ImportanceInnate immunity serves as the first barrier against virus infection. DEAD (Glu-Asp-Ala-Glu)-box RNA helicases, originally considered to be involved RNA processing and RNA unwinding, have been shown to play an important role in anti-viral innate immunity. The precise regulation of innate immunity is critical for the host because the aberrant production of cytokines leads to unexpected pathological consequences. Here, we identified DDX21 was cleaved at D126 by virus infection and treatment with RNA/DNA ligands via the caspase-3/6-dependent pathway. The cytoplasmic cleaved DDX21 negatively regulates the IFN-{beta} signaling pathway by suppressing the formation of DDX1-DDX21-DHX36 complex. In sum, our data identify DDX21 as a regulator of immune balance and most importantly uncover a potential role of DDX21 cleavage in the innate immunity response towards virus.

microbiology↗

bioRxiv2021

Genomic and epigenomic adaptation in SP-R210 (Myo18A) isoform-deficient macrophages

1Macrophages play fundamental roles in regulation of inflammatory responses to pathogens, resolution of inflammation and tissue repair, and maintenance of tissue homeostasis. The long (L) and short (S) isoforms of SP-R210/MYO18A, a macrophage receptor for surfactant protein A (SP-A) and C1q, regulate basal and inflammatory macrophage phenotype at multiple gene expression, translational, and subcellular levels in addition to their SP-A and C1q-mediated functions; disruption of L renders macrophages hyper-inflammatory, although the underlying mechanism had previously been unexplored. We asked whether disruption of the L isoform led to the hyper-inflammatory state via alteration of global genomic responses. RNA sequencing analysis of SP-R210L(DN) macrophages revealed basal and influenza induced upregulation of genes associated with inflammatory pathways, including TLR, RIG-I, NOD, and cytoplasmic DNA signaling, whereas knockdown of both SP-R210 isoforms (L and S) only resulted in increased RIG-I and NOD signaling. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis showed increased genome-wide deposition of the pioneer transcription factor PU.1 in SP-R210L(DN) compared to WT cells. ChIP-seq analysis of histone H3 methylation showed alterations in both repressive (H3K9me3 and H3K27me3) and transcriptionally active (H3K9me3) histone marks. Influenza A virus (IAV) infection, which stimulates an array of cytosolic and TLR-mediated antiviral mechanisms, resulted in differential redistribution between proximal promoter and distal sites and decoupling of PU.1 binding from Toll-like receptor regulated gene promoters in SP-R210L(DN) cells. Our findings suggest that SP-R210L-deficient macrophages are poised with an open PU.1-primed chromatin conformation to rapidly respond to inflammatory and metabolic stimuli.

immunology↗

bioRxiv2021

Untangling the complexity of priority effects in multi-species communities

The history of species immigration can dictate how species interact in local communities, thereby causing historical contingency in community assembly. Since immigration history is rarely known, these historical influences, or priority effects, pose a major challenge in predicting community assembly. Here, we provide a graph-based, non-parametric, theoretical framework for understanding the predictability of community assembly as affected by priority effects. To develop this frame-work, we first show that the diversity of possible priority effects increases super-exponentially with the number of species. We then point out that, despite this diversity, the consequences of priority effects for multispecies communities can be classified into four basic types, each of which reduces community predictability: alternative stable states, alternative transient paths, compositional cycles, and the lack of escapes from compositional cycles to stable states. Using a neural network, we show that this classification of priority effects enables accurate explanation of community predictability, particularly when each species immigrates repeatedly. We also demonstrate the empirical utility of our theoretical framework by applying it to two experimentally derived assembly graphs of algal and ciliate communities. Based on these analyses, we discuss how the framework proposed here can help guide experimental investigation of the predictability of history-dependent community assembly.

ecology↗

bioRxiv2021

Deep neural network analysis employing diffusion basis spectrum imaging metrics as classifiers improves prostate cancer detection and grading

Structural and cellular complexity of prostatic histopathology limits the accuracy of noninvasive detection and grading of prostate cancer (PCa). We addressed this limitation by employing a novel diffusion basis spectrum imaging (DBSI) to derive structurally-specific diffusion fingerprints reflecting various underlying prostatic structural and cellular components. We further developed diffusion histology imaging (DHI) by combining DBSI-derived structural fingerprints with a deep neural network (DNN) algorithm to more accurately classify different histopathological features and predict tumor grade in PCa. We examined 243 patients suspected with PCa using in vivo DBSI. The in vivo DBSI-derived diffusion metrics detected coexisting prostatic pathologies distinguishing inflammation, PCa, and benign prostatic hyperplasia. DHI distinguished PCa from benign peripheral and transition zone tissues with over 95% sensitivity and specificity. DHI also demonstrated over 90% sensitivity and specificity for Gleason score noninvasively. We present DHI as a novel diagnostic tool capable of noninvasive detection and grading of PCa. One sentence summaryDiffusion histology imaging noninvasively and accurately detects and grades prostate cancer.

bioinformatics↗