Biology subjects

Yao, L.

Publications and source records attributed to Yao, L..

At least 109 records · Page 6Linked to original sources

bioRxiv2022

Capped nascent RNA sequencing reveals novel therapy-responsive enhancers in prostate cancer

Mounting evidence suggests that enhancer RNA (eRNA) transcription start sites (TSSs) provide higher sensitivity and specificity for enhancer identification than histone modifications and chromatin accessibility. The extent to which changes in eRNA transcription correspond to changes in enhancer activity, however, remains unclear. Here, we used precision run-on and capped RNA sequencing (PRO-cap) to assess changes in enhancer activity in response to treatment with the androgen receptor signaling inhibitor, enzalutamide (ENZ). We identified 6,189 high-confidence candidate enhancers in the human prostate cancer cell line, LNCaP; 853 of which demonstrated significant changes in activity in response to drug treatment. Notably, we found that 67% and 54% of drug-responsive enhancers did not show similar changes in activity in previous studies that utilized ChIP-seq and ATAC-seq, respectively. Strikingly, 79% of regions with increased eRNA transcription showed no other biochemical alterations, implying that PRO-cap can capture a set of precise changes in enhancer activity that classical approaches lack the sensitivity to detect. We performed in vivo functional validations of candidate enhancers and found that CRISPRi targeting of PRO-cap-specific drug-responsive enhancers impaired ENZ regulation of downstream target genes, suggesting that changes in eRNA TSSs mark true biological changes in enhancer activity with high sensitivity. Our study highlights the utility of using PRO-cap as a complementary approach to canonical biochemical methods for detecting precise changes in enhancer activity and, in particular, for better understanding disease progression and responses to treatment.

genomics↗

bioRxiv2022

An overlapped natural antisense lncRNA FCER1A-AS controls anaphylactic reaction by promoting FcϵRIα expression

Functioned as -subunit of the high-affinity immunoglobulin E receptor (Fc{varepsilon} RI), Fc{varepsilon} RI plays a central role in the pathogenesis of Ig-E-mediated allergy and other IgE-related disorders. Fc{varepsilon} RI is normally expressed only in limited spectrum of cells like basophils and mast cells, but the mechanism of controlling Fc{varepsilon} RI expression in these cells is less well understood. In this study, we found fully overlapped natural antisense transcript (NATs) of Fc{varepsilon} RI (FCER1A-AS) is co-expressed with cognate sense transcript (FCER1A-S) in IL-3 induced Fc{varepsilon} RI-expressing cells or in high Fc{varepsilon} RI-expressing cell line MC/9. When FCER1A-AS is selectively knocked down by CRISPR/RfxCas13d (CasRx) approach in MC/9, expression of mRNA and proteins of FCER1A-S is also markedly decreased. Furthermore, deficiency of FCER1A-AS along with lack of FCER1A-S expression is found in two different lines of gene-targeted mice in which FCER1A locus is disturbed at different sites. More importantly, the FCER1A-AS-deficient homozygous mice display similarly diminished anaphylactic reaction as FCER1A gene knockout mice. Thus, we uncovered in this investigation that the expression of FCER1A-S is positively regulated by co-expressed fully overlapped antisense transcript.

immunology↗

bioRxiv2022

Neuronopathic GBA1 L444P mutation accelerates glucosylsphingosine levels and formation of hippocampal alpha-synuclein inclusions

The most common genetic risk factor for Parkinsons disease (PD) is heterozygous mutations in the GBA1 gene which encodes for the lysosomal enzyme, glucocerebrosidase (GCase). GCase impairments are associated with an accumulation of abnormal -synuclein (-syn) called Lewy pathology, which characterizes PD. PD patients heterozygous for the GBA1 L444P mutation (GBA1+/L444P) have a 5.6-fold increased risk of cognitive impairments. In this study, we used GBA1+/L444P mice to determine the effects of this severe GBA1 mutation on lipid metabolism, expression of synaptic proteins, behavior, and -syn inclusion formation. GBA1+/L444P mice showed reduced GCase activity in limbic brain regions and expressed lower levels of hippocampal vGLUT1 compared to wildtype (GBA1+/+) mice. GBA+/L444P mice also demonstrated impaired fear conditioning, but no motor deficits. We show, using mass spectrometry, that mutant GCase and age increased levels of glucosylsphingosine (GlcSph), but not glucosylceramide (GlcCer), in the brains and serum of GBA1+/L444P mice. Aged GBA1+/+ mice also showed increased levels of GlcSph, and decreased GlcCer. To model disease pathology, templated -syn pathology was used. -Syn inclusions were increased in the hippocampus of GBA1+/L444P mice compared to GBA1+/+ mice, but not in the cortex, or substantia nigra pars compacta (SNc). Pathologic -syn did not cause a loss of dopamine neurons in the SNc. Treatment with a GlcCer synthase inhibitor prevented loss of cortical -syn inclusions, but not loss of dopamine neurons. Overall, these data suggest the critical importance to evaluate the contribution of hippocampal pathologic -syn and brain and serum glucosylsphingosine in synucleinopathies. SIGNIFICANCE STATEMENTSynucleinopathies, such as Parkinsons disease (PD) and Dementia with Lewy bodies (DLB), are both pathologically characterized by abnormal -synuclein (-syn). Mutant GBA1 is a risk factor for both PD and DLB where a reduction of glucocerebrosidase (GCase) activity is seen. Collectively, this indicates the significance of evaluating mutant GCase in synucleinopathies. Our data suggest the critical importance to evaluate the contribution of hippocampal pathologic -syn and brain and serum glucosylsphingosine (GlcSph) accumulation in synucleinopathies. Moreover, these pathologic outcomes may contribute to the nonmotor symptoms clinically observed in PD and DLB. Our findings highlight the importance of GlcSph as a relevant biomarker for future therapeutics.

neuroscience↗

bioRxiv2022

Bi-steric mTORC1-selective Inhibitors activate 4EBP1 reversing MYC-induced tumorigenesis and synergize with immunotherapy

The MYC oncogene is causally involved in the pathogenesis of most types of human cancer but it remains therapeutically untargeted. The mTORC1 protein complex regulates cap-dependent translation through 4EBP1 and S6K and thereby, downstream MYC protein expression. However, to date, agents such as rapalogs that selectively target mTORC1 (as compared to mTORC2) fail to reactivate 4EBP1 and thus, to block MYC in vivo. In contrast, agents that nonselectively inhibit both protein complexes of the mTOR pathway, mTORC1 and mTORC2, can activate 4EBP1, but often suffer from a lack of tolerability including in vivo hepatotoxicity and immunosuppression. Here, we report the anti-tumor activity of bi-steric mTORC1-selective inhibitors, including Revolution Medicines clinical candidate RMC-5552, that potently and selectively target mTORC1 over mTORC2. In an autochthonous transgenic mouse model of MYC-amplified and MYC-driven hepatocellular carcinoma (HCC), representative bi-steric mTORC1-selective inhibitors suppress translation initiation via activation of 4EBP1, thereby suppressing MYC protein expression and blocking tumor growth. Furthermore, in human HCC samples, the low levels of 4EBP1 and MYC is correlated with immune reactivation. Immunohistochemistry, CIBERSORT, and CODEX reveal that selective mTORC1 inhibition results in activation of both CD4+ T cell- and NKp46+ NK cell-mediated immune surveillance. Moreover, bi-steric mTORC1-selective inhibitors synergize with -PD-1 to induce sustained tumor regression, with immune cell degranulation and release of perforins and granzyme B. These agents also exhibit anti-tumor activity in human patient-derived xenografts of HCC, colorectal cancer, head and neck cancer, and ovarian cancer harboring genomic amplifications in MYC. We infer that selective mTORC1 inhibition is a potential therapeutic strategy to drive effective MYC inactivation in cancer, and the consequent restoration of immune surveillance against neoplasia.

cancer biology↗

bioRxiv2022

Comparing the folding landscapes of evolutionarily divergent procaspase-3

All caspases evolved from a common ancestor and subsequently developed into two general classes, inflammatory or apoptotic caspases. The caspase-hemoglobinase fold has been conserved throughout nearly one billion years of evolution and is utilized for both the monomeric and dimeric subfamilies of apoptotic caspases, called initiator and effector caspases, respectively. We compared the folding and assembly of procaspase-3b from zebrafish to that of human effector procaspases in order to examine the conservation of the folding landscape. Urea-induced equilibrium folding/unfolding of procaspase-3b showed a minimum three-state folding pathway, where the native dimer isomerizes to a partially folded dimeric intermediate, which then unfolds. A partially folded monomeric intermediate observed in the folding landscape of human procaspase-3 is not well-populated in zebrafish procaspase-3b. By comparing effector caspases from different species, we show that the effector procaspase dimer undergoes a pH-dependent conformational change, and that the conformational species in the folding landscape exhibit similar free energies. Together, the data show that the landscape for the caspase-hemoglobinase fold is conserved, yet it provides flexibility for species-specific stabilization or destabilization of folding intermediates resulting in changes in stability. The common pH-dependent conformational change in the native dimer, which yields an enzymatically inactive species, may provide an additional, albeit reversible, mechanism for controlling caspase activity in the cell.

biophysics↗

bioRxiv2021

A novel high-throughput assay using mixed genomic DNA for fast screening germline pathogenic variants in breast cancer susceptibility genes

The demand for genetic testing for breast cancer susceptibility genes is increasing for both breast cancer patients and healthy individuals. Here we established a novel high-throughput assay to detect germline pathogenic variants in breast cancer susceptibility genes. In general, up 10 to 50 individual genomic DNA samples were mixed together to create a mixed DNA sample and the mixed DNA sample was subjected to a next-generation multigene panel. Germline pathogenic variants in breast cancer susceptibility genes could be found in the mixed DNA sample; next, site-specific Sanger sequencing was performed to identify individuals who carried he pathogenic variant in the mixed samples. We found that the recall and precision rates were 89.9% and 92.9% when twenty individual genomic samples were mixed. Therefore, our new assay can increase an approximately 20-fold of efficacy to identify the pathogenic variants in breast cancer susceptibility genes in individuals when compared with current assay.

genetics↗

bioRxiv2021

KinasePhos 3.0: Redesign and Expansion of the Prediction on Kinase-specific Phosphorylation Sites

The purpose of this work is to enhance KinasePhos, a machine-learning-based kinase-specific phosphorylation site prediction tool. Experimentally verified kinase-specific phosphorylation data were collected from PhosphoSitePlus, UniProt, GPS 5.0, and Phospho.ELM. In total, 41,421 experimentally verified kinase-specific phosphorylation sites were identified. A total of 1380 unique kinases were identified, including 753 with existing classification information from KinBase and the remaining 627 annotated by building a phylogenetic tree. Based on this kinase classification, a total of 771 predictive models were built at the individual, family, and group levels, using at least 15 experimentally verified substrate sites in positive training datasets. The improved models were observed to be more effective than other prediction tools. For example, the prediction of sites phosphorylated by the Akt, CKT, and PKA families had accuracies of 94.5%, 92.5%, and 90.0%, respectively. The average prediction accuracy for all 771 models was 87.2%. For enhancing interpretability, the Shapley additive explanations (SHAP) method was employed to assess feature importance. The web interface of KinasePhos 3.0 has been redesigned with the goal of providing comprehensive annotations of kinase-specific phosphorylation sites on multiple proteins. Additionally, considering the large scale of phosphoproteomic data, a downloadable prediction tool is available at https://awi.cuhk.edu.cn/KinasePhos/index.html or https://github.com/tom-209/KinasePhos-3.0-executable-file.

bioinformatics↗

bioRxiv2021

Extrasynaptic NMDA receptors bidirectionally modulate intrinsic excitability of inhibitory neurons

The NMDA subtype glutamate receptors (NMDARs) play important roles in both physiological and pathological processes in the brain. Comparing to their critical roles in synaptic modifications and excitotoxicity in the excitatory neurons, much less is understood about the functional contributions of NMDARs to the inhibitory/GABAergic neurons. By using selective NMDAR inhibitors and potentiators, we here show that NMDARs bi-directionally modulate the intrinsic excitability (defined as spontaneous/evoked spiking activity and EPSP-spike coupling) in the inhibitory/GABAergic neurons. This modulation depends on GluN2C/2D-but not GluN2A/2B-containing NMDARs. We further show that NMDAR modulator EU1794-4 mostly enhances extrasynaptic NMDAR activity, and by using it we demonstrate a significant contribution of extrasynaptic NMDARs to the modulation of intrinsic excitability in the inhibitory neurons. Altogether, this bidirectional modulation of intrinsic excitability reveals a previously less appreciated importance of NMDARs in the second-to-second functioning of inhibitory/GABAergic neurons.

neuroscience↗

bioRxiv2021

A semisynthetic glycoconjugate provides expanded cross-serotype protection against Streptococcus pneumoniae

Streptococcus pneumoniae infections are the leading cause of child mortality globally. Current vaccines fail to induce a protective immune response towards a conserved part of the pathogen, resulting in new serotypes causing disease. Therefore, new vaccine strategies are urgently needed. Described is a two-pronged approach combining S.pneumoniae proteins, pneumolysin and PspA, with a precisely defined synthetic oligosaccharide, whereby the carrier protein acts as a serotype-independent antigen to provide additional protection. Proof of concept in mice and swine models revealed that the conjugates inhibit colonization of the nasopharynx, decrease the bacterial load and reduce disease severity in the bacteria challenged model. Immunization of piglets provided the first evidence for the immunogenicity and protective potential of synthetic glycoconjugate vaccine in a large animal model. A combination of synthetic oligosaccharides with proteins from the target pathogen opens the path to create broadly cross-protective ("universal") pneumococcal vaccines.

immunology↗

bioRxiv2021

Systematic comparison of experimental assays and analytical pipelines for identification of active enhancers genome-wide

Mounting evidence supports the idea that transcriptional patterns serve as more specific identifiers of active enhancers than histone marks1,2; however, the optimal strategy to identify active enhancers both experimentally and computationally has not been determined. In this study, we compared 13 genome-wide RNA sequencing assays in K562 cells and showed that the nuclear run-on followed by cap-selection assay (namely, GRO/PRO-cap) has significant advantages in eRNA detection and active enhancer identification. We also introduced a new analytical tool, Peak Identifier for Nascent-Transcript Sequencing (PINTS), to identify active promoters and enhancers genome-wide and pinpoint the precise location of the 5 transcription start sites (TSSs) within these regulatory elements. Finally, we compiled a comprehensive enhancer candidate compendium based on the detected eRNA TSSs available in 120 cell and tissue types. To facilitate the exploration and prioritization of these enhancer candidates, we also built a user-friendly web server (https://pints.yulab.org) for the compendium with various additional genomic and epigenomic annotations. With the knowledge of the best available assays and pipelines, this large-scale annotation of candidate enhancers will pave the road for selection and characterization of their functions in a time-, labor-, and cost-effective manner in the future.

genomics↗

bioRxiv2021

Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis

Extracellular matrix (ECM) stiffening with downstream activation of mechanosensitive pathways is strongly implicated in fibrosis. We previously reported that altered collagen nanoarchitecture is a key determinant of pathogenetic ECM structure-function in human fibrosis (Jones et al., 2018). Here, through human tissue, bioinformatic and ex vivo studies we show that hypoxia-inducible factor (HIF) pathway activation is a critical pathway for this process regardless of oxygen status (pseudohypoxia). Whilst TGF{beta} increased rate of fibrillar collagen synthesis, HIF pathway activation was required to dysregulate post-translational modification of fibrillar collagen, promoting bone-type cross-linking, altering collagen nanostructure, and increasing tissue stiffness. In vitro, knock down of Factor Inhibiting HIF (FIH) or oxidative stress caused pseudohypoxic HIF activation in normal fibroblasts. In contrast, endogenous FIH activity was reduced in fibroblasts from patients with lung fibrosis in association with significantly increased normoxic HIF pathway activation. In human lung fibrosis tissue, HIF mediated signalling was increased at sites of active fibrogenesis whilst subpopulations of IPF lung mesenchymal cells had increases in both HIF and oxidative stress scores. Our data demonstrate that oxidative stress can drive pseudohypoxic HIF pathway activation which is a critical regulator of pathogenetic collagen structure-function in fibrosis.

cell biology↗

bioRxiv2021

Multi-omics prediction of oat agronomic and seed nutritional traits across environments and in distantly related populations

Multi-omics prediction has been shown to be superior to genomic prediction with genome-wide DNA-based genetic markers (G) for predicting phenotypes. However, most of the existing studies were based on historical datasets from one environment; therefore, they were unable to evaluate the efficiency of multi-omics prediction in multi-environment trials and distantly-related populations. To fill those gaps, we designed a systematic experiment to collect omics data and evaluate 17 traits in two oat breeding populations planted in single and multiple environments. In the single-environment trial, transcriptomic BLUP (T), metabolomic BLUP (M), G+T, G+M and G+T+M models showed greater prediction accuracy than GBLUP for 5, 10, 11, 17 and 17 traits, respectively, and metabolites generally performed better than transcripts when combined with SNPs. In the multi-environment trial, multi-trait models with omics data outperformed both counterpart multi-trait GBLUP models and single-environment omics models, and the highest prediction accuracy was achieved when modeling genetic covariance as an unstructured covariance model. We also demonstrated that omics data can be used to prioritize loci from one population with omics data to improve genomic prediction in a distantly-related population using a two-kernel linear model that accommodated both likely casual loci with large-effect and loci that explain little or no phenotypic variance. We propose that the two-kernel linear model is superior to most genomic prediction models that assume each variant is equally likely to affect the trait and can be used to improve prediction accuracy for any trait with prior knowledge of genetic architecture.

genetics↗

bioRxiv2021

Spatial drivers and pre-cancer populations collaborate with the microenvironment in untreated and chemo-resistant pancreatic cancer

Pancreatic Ductal Adenocarcinoma (PDAC) is a lethal disease with limited treatment options and poor survival. We studied 73 samples from 21 patients (7 treatment-naive and 14 treated with neoadjuvant regimens), analyzing distinct spatial units and performing bulk proteogenomics, single cell sequencing, and cellular imaging. Spatial drivers, including mutant KRAS, SMAD4, and GNAQ, were associated with differential phosphosignaling and metabolic responses compared to wild type. Single cell subtyping discovered 12 of 21 tumors with mixed basal and classical features. Trefoil factor family members were upregulated in classical populations, while the basal populations showed enhanced expression of mesenchymal genes, including VIM and IGTB1. Acinar-ductal metaplasia (ADM) populations, present in 95% of patients, with 46% reduction of driver mutation fractions compared to tumor populations, exhibited suppressive and oncogenic features linked to morphologic states. We identified coordinated expression of TIGIT in exhausted and regulatory T cells and Nectin receptor expression in tumor cells. Higher expression of angiogenic and stress response genes in dendritic cells compared to tumor cells suggests they have a pro-tumorigenic role in remodeling the microenvironment. Treated samples contain a three-fold enrichment of inflammatory CAFs when compared to untreated samples, while other CAF subtypes remain similar. A subset of tumor and/or ADM-specific biomarkers showed differential expression between treatment groups, and several known drug targets displayed potential cross-cell type reactivities. This resolution that spatially defined single cell omics provides reveals the diversity of tumor and microenvironment populations in PDAC. Such understanding may lead to more optimal treatment regimens for patients with this devastating disease. HIGHLIGHTSO_LIAcinar-ductal metaplasia (ADM) cells represent a genetic and morphologic transition state between acinar and tumor cells. C_LIO_LIInflammatory cancer associated fibroblasts (iCAFs) are a major component of the PDAC TME and are significantly higher in treated samples C_LIO_LIReceptor-ligand analysis reveals tumor cell-TME interactions through NECTIN4-TIGIT C_LIO_LITumor and ADM cell proteogenomics differ between treated and untreated samples, with unique and shared potential drug targets C_LI

cancer biology↗

bioRxiv2021

ADAM10- and presenilin 1/γ-secretase-dependent cleavage of PTPRT mitigates neurodegeneration of Alzheimer's disease

PTPRT (receptor-type tyrosine-protein phosphatase T), as a brain-specific type 1 transmembrane protein, plays an important function in neurodevelopment and synapse formation. However, whether PTPRT-dependent signaling is involved in Alzheimers disease (AD) remains elusive. Here, we identified that PTPRT intracellular domain (PICD), which was released from ADAM10- and presenilin 1-/{gamma}-secretase-dependent cleavage of PTPRT, efficiently translocated to the nucleus via a conserved nuclear localization signal. Inhibition of nuclear localization of PICD via the mutation of its nuclear localization signal (NLS) leads to accumulation of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), which is a substrate of PTPRT and eventually resulted in neuronal cell death. Consistently, RNA sequencing reveals that expression of the PICD alone can profoundly alter the expression of genes associated with synapse function and dephosphorylation, phosphatase and cell adhesion. Unexpectedly, the downregulated levels of Ptprt mRNA and protein were found in both human and mouse AD brains. Finally, overexpression of PICD alone not only significantly decreases the level of phosph-STAT3Y705 and A{beta} deposition in the hippocampus of APP/PS1 mice, but also improves synaptic function and behavioral deficits in APP/PS1 mice. Our findings suggest that a novel role of the ADAM 10- and presenilin 1-/{gamma}-secretase-dependent cleavage of PTPRT in the events can mitigate neurodegeneration of AD and moderate Alzheimers pathogenesis.

neuroscience↗

bioRxiv2021

Human gut bacteria produce TH17-modulating bile acid metabolites

The microbiota plays a pivotal role in gut immune homeostasis. Bacteria influence the development and function of host immune cells, including T helper cells expressing interleukin-17a (TH17 cells). We previously reported that the bile acid metabolite 3-oxolithocholic acid (3-oxoLCA) inhibits TH17 cell differentiation1. While it was suggested that gut-residing bacteria produce 3-oxoLCA, the identity of such bacteria was unknown. Furthermore, it was not clear whether 3-oxoLCA and other immunomodulatory bile acids are associated with gut inflammatory pathologies in humans. Using a high-throughput screen, we identified human gut bacteria and corresponding enzymes that convert the secondary bile acid lithocholic acid into 3-oxoLCA as well as the abundant gut metabolite isolithocholic acid (isoLCA). Like 3-oxoLCA, isoLCA suppressed TH17 differentiation by inhibiting ROR{gamma}t (retinoic acid receptor-related orphan nuclear receptor {gamma}t), a key TH17 cell-promoting transcription factor. Levels of both 3-oxoLCA and isoLCA and the 3-hydroxysteroid dehydrogenase (3-HSDH) genes required for their biosynthesis were significantly reduced in patients with inflammatory bowel diseases (IBD). Moreover, levels of these bile acids were inversely correlated with expression of TH17 cell-associated genes. Overall, our data suggest that bacterially produced TH17 cell-inhibitory bile acids may reduce the risk of autoimmune and inflammatory disorders such as IBD.

immunology↗

bioRxiv2021

A Bacterial Bile Acid Metabolite Modulates Treg Activity through the Nuclear Hormone Receptor NR4A1

Bile acids act as signaling molecules that regulate immune homeostasis, including the differentiation of CD4+ T cells into distinct T cell subsets. The bile acid metabolite isoallolithocholic acid (isoalloLCA) enhances the differentiation of anti-inflammatory regulatory T cells (Treg cells) by facilitating the formation of a permissive chromatin structure in the promoter region of the transcription factor forkhead box P3 (Foxp3). Here, we identify gut bacteria that synthesize isoalloLCA from 3-oxolithocholic acid and uncover a gene cluster responsible for the conversion in members of the abundant human gut bacterial phylum Bacteroidetes. We also show that the nuclear hormone receptor NR4A1 is required for the effect of isoalloLCA on Treg cells. Moreover, the levels of isoalloLCA and its biosynthetic genes are significantly reduced in patients with inflammatory bowel diseases, suggesting that isoalloLCA and its bacterial producers may play a critical role in maintaining immune homeostasis in humans.

immunology↗

bioRxiv2020

MEMS directed evolution of two cytochrome P450 enzymes revealing distinct active-sites for convergent function

Directed evolution (DE) inspired by natural evolution (NE) has been achieving tremendous successes in protein/enzyme engineering. However, the conventional one-protein-for-one-task DE cannot match the multi-proteins-for-multi-tasks NE in terms of screening throughput and efficiency, thus often failing to meet the fast-growing demands for biocatalysts with desired properties. In this study, we design a novel multi-enzyme-for-multi-substrate (MEMS) DE model and establish the proof-of-concept by running a NE-mimicking and higher-throughput screening on the basis of two-P450s-against-seven-substrates (2Px7S) in one pot. With the significantly improved throughput and hit-rate, we witness a series of convergent evolution events of the two archetypal cytochrome P450 enzymes (P450 BM3 and P450cam) in laboratory. Further structural analysis of the two functionally convergent P450 variants provide important insights into how distinct active-sites can reach a common catalytic goal.

biochemistry↗

bioRxiv2020

The Wood Image Analysis and Dataset (WIAD): open-access visual analysis tools to advance the ecological data revolution

O_LIEcological data is collected and shared at an increasingly rapid pace, but it is often shared in inconsistent and untraceable processed forms. Images of wood contain a wealth of information such as colours and textures but are most commonly reduced to ring-width measurements before they can be shared in various common file formats. Archiving digital images of wood samples in libraries, that have been developed for ecological analysis and are publicly available, remains the exception. C_LIO_LIWe developed the Wood Image Analysis and Dataset (WIAD) an open-source application including a web-interface to integrate basic visual analysis of wood samples, such as increment cores, thin sections or x-ray films, basic data processing, and archiving of the images and derived data to facilitate transparency and reproducibility in studies using visual characteristics of wood. C_LIO_LIWIAD provides user-friendly tools to manipulate images of wood samples, mark and measure wood characteristics such as growth increments, density fluctuations, early- and latewood widths, and fire scars, and to visualise, process, and archive images, metadata, and the derived data. C_LIO_LIWIAD constitutes a step towards the reproducible automation of tree-ring analysis, while establishing an open-source foundation to create improved community developed repositories which would enable novel ecological studies harnessing the wealth of existing visual data. C_LI

plant biology↗