The Polygenic Score Catalog: new functionality and tools to enable FAIR research.

Polygenic scores (PGS) have transformed human genetic research and have multiple potential clinical applications, including risk stratification for disease prevention and prediction of treatment response. Here, we present a series of recent enhancements to the PGS Catalog (www.PGSCatalog.org), the largest findable, accessible, interoperable, and reusable (FAIR) repository of PGS. These include expansions in data content and ancestral diversity as well as the addition of new features. We further present the PGS Catalog Calculator (pgsc_calc, https://github.com/PGScatalog/pgsc_calc), an open-source, scalable and portable pipeline to reproducibly calculate PGS that securely democratizes equitable PGS applications by implementing genetic ancestry estimation and score normalization using reference data. With the PGS Catalog & calculator users can now quantify an individual's genetic predisposition for hundreds of common diseases and clinically relevant traits. Taken together, these updates and tools facilitate the next generation of PGS, thus lowering barriers to the clinical studies necessary to identify where PGS may be integrated into clinical practice.

The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource.

The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to >200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for >45 000 published GWAS across >5000 human traits, and >40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.

A joint NCBI and EMBL-EBI transcript set for clinical genomics and research.

Comprehensive genome annotation is essential to understand the impact of clinically relevant variants. However, the absence of a standard for clinical reporting and browser display complicates the process of consistent interpretation and reporting. To address these challenges, Ensembl/GENCODE1 and RefSeq2 launched a joint initiative, the Matched Annotation from NCBI and EMBL-EBI (MANE) collaboration, to converge on human gene and transcript annotation and to jointly define a high-value set of transcripts and corresponding proteins. Here, we describe the MANE transcript sets for use as universal standards for variant reporting and browser display. The MANE Select set identifies a representative transcript for each human protein-coding gene, whereas the MANE Plus Clinical set provides additional transcripts at loci where the Select transcripts alone are not sufficient to report all currently known clinical variants. Each MANE transcript represents an exact match between the exonic sequences of an Ensembl/GENCODE transcript and its counterpart in RefSeq such that the identifiers can be used synonymously. We have now released MANE Select transcripts for 97% of human protein-coding genes, including all American College of Medical Genetics and Genomics Secondary Findings list v3.0 (ref. 3) genes. MANE transcripts are accessible from major genome browsers and key resources. Widespread adoption of these transcript sets will increase the consistency of reporting, facilitate the exchange of data regardless of the annotation source and help to streamline clinical interpretation.

Use of a new zwitterionic cellulose derivative for removal of crystal violet and orange II from aqueous solutions.

This study describes the synthesis of a new bioadsorbent with zwitterionic characteristics and its successful application for removal of a cationic dye (crystal violet, CV) and an anionic dye (orange II, OII) from single component aqueous systems. The new bi-functionalized cellulose derivative (MC3) was produced by chemical modification of cellulose with succinic anhydride and choline chloride to introduce carboxylic and quaternary ammonium functional groups on the cellulose surface. MC3 was characterized by several wet chemical and spectroscopic methods. The effects of solution pH, contact time, and initial solute concentration on removal of CV and OII by MC3 were investigated. Studies of the desorption and re-adsorption of the dyes were also carried out. The isotherms for adsorption of CV and OII on MC3 were satisfactorily fitted using the Konda and Langmuir models. MC3 showed experimental maximum adsorption capacities of 2403 mg g-1 for CV and 201 mg g-1 for OII. The desorption and re-adsorption results showed that MC3 could be reused in successive adsorption cycles, which is essential for minimizing process costs and waste generation. The findings showed that MC3 is a versatile biosorbent capable of efficiently removing both cationic and anionic dyes.

Application of pyridine-modified chitosan derivative for simultaneous adsorption of Cu(II) and oxyanions of Cr(VI) from aqueous solution.

The bioadsorbent C1, which is a chitosan derivative prepared in a one-step synthesis, was successfully used to adsorb Cr(VI) and Cu(II) simultaneously. Here, for the first time the simultaneous adsorption of a cation and an anion was modeled using the Corsel model for kinetics and the Real Adsorbed Solution Theory model for equilibrium data. Batch studies of the adsorption of Cu(II) and Cr(VI) in single and binary aqueous solutions were performed as a function of initial solute concentration, contact time, and solution pH. The maximum adsorption capacities of C1 in single and binary aqueous solutions were 1.84 and 1.13 mmol g-1 for Cu(II) and 3.86 and 0.98 mmol g-1 for Cr(VI), respectively. The reuse of C1 was investigated, with Cu(II) ions being almost completely desorbed and fully re-adsorbed. For Cr(VI), the desorption was incomplete resulting in a lower re-adsorption. Energy-dispersive X-ray spectroscopy was used for mapping the distributions of Cr(VI) and Cu(II) adsorbed on the C1 surface in single and binary adsorption systems. Isothermal titration calorimetry experiments were performed for Cr(VI) and Cu(II) adsorption in single solutions. The thermodynamic parameters of adsorption showed that the adsorption of both metal ions was enthalpically driven, but entropically unfavorable.

Ensembl Genomes 2020-enabling non-vertebrate genomic research.

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of interfaces to genomic data across the tree of life, including reference genome sequence, gene models, transcriptional data, genetic variation and comparative analysis. Data may be accessed via our website, online tools platform and programmatic interfaces, with updates made four times per year (in synchrony with Ensembl). Here, we provide an overview of Ensembl Genomes, with a focus on recent developments. These include the continued growth, more robust and reproducible sets of orthologues and paralogues, and enriched views of gene expression and gene function in plants. Finally, we report on our continued deeper integration with the Ensembl project, which forms a key part of our future strategy for dealing with the increasing quantity of available genome-scale data across the tree of life.

Ensembl 2020.

The Ensembl (https://www.ensembl.org) is a system for generating and distributing genome annotation such as genes, variation, regulation and comparative genomics across the vertebrate subphylum and key model organisms. The Ensembl annotation pipeline is capable of integrating experimental and reference data from multiple providers into a single integrated resource. Here, we present 94 newly annotated and re-annotated genomes, bringing the total number of genomes offered by Ensembl to 227. This represents the single largest expansion of the resource since its inception. We also detail our continued efforts to improve human annotation, developments in our epigenome analysis and display, a new tool for imputing causal genes from genome-wide association studies and visualisation of variation within a 3D protein model. Finally, we present information on our new website. Both software and data are made available without restriction via our website, online tools platform and programmatic interfaces (available under an Apache 2.0 license) and data updates made available four times a year.

Trimellitated sugarcane bagasse: A versatile adsorbent for removal of cationic dyes from aqueous solution. Part II: Batch and continuous adsorption in a bicomponent system.

In the second part of this series of studies, the bicomponent adsorption of safranin-T (ST) and auramine-O (AO) on trimellitated sugarcane bagasse (STA) was evaluated using equimolar dye aqueous solutions at two pH values. Bicomponent batch adsorption was investigated as a function of contact time, solution pH and initial concentration of dyes. Bicomponent kinetic data were fitted by the pseudo-first-order and pseudo-second-order models and the competitive model of Corsel. Bicomponent equilibrium data were fitted by the real adsorbed solution theory model. The antagonistic interactions between ST and AO in the adsorption systems studied contributed to obtain values of maximum adsorption capacity in mono- (Qmax,mono) and bicomponent (Qmax,multi) lower than unity (Qmax,multi/Qmax,mono at pH 4.5 for ST of 0.75 and AO of 0.37 and at pH 7 for ST of 0.94 and AO of 0.43). Mono- and bicomponent adsorption of dyes in a fixed-bed column was evaluated at pH 4.5. The breakthrough curves were fitted by the Thomas and Bohart-Adams original models. Desorption of ST in a fixed-bed column was studied. The results obtained from the bicomponent batch and continuous adsorption showed that the presence of ST most affected the AO adsorption than the presence of AO affected the ST adsorption.

Synthesis and application of sugarcane bagasse cellulose mixed esters. Part II: Removal of Co2+ and Ni2+ from single spiked aqueous solutions in batch and continuous mode.

Sugarcane bagasse cellulose succinate trimellitate (SBST) was prepared by a one-pot synthesis method. The synthesis of this novel mixed ester was investigated by a 23-factorial design. The parameters investigated were time, temperature, and succinic anhydride mole fraction (χSA). The responses evaluated were the adsorption capacity (qCo2+ and qNi2+), weight gain (wg), and number of carboxylic acid groups (nT,COOH). 13C Multiple Cross-Polarization solid-state NMR spectroscopy, 1H NMR relaxometry, and Fourier-transform infrared spectroscopy were used to elucidate the SBST structure. The best SBST reaction conditions were 100 °C, 660 min, and χSA of 0.2, which yielded SBST with a wg of 57.1%, nT,COOH of 4.48 mmol g-1, and qCo2+ and qNi2+ of 0.900 and 0.963 mmol g-1, respectively. The maximum adsorption capacities (Qmax) (pH 5.75, 25 °C) estimated by the Redlich-Peterson model for Co2+ and Ni2+ were 1.16 and 1.29 mmol g-1. The ΔadsH° values for Co2+ and Ni2+ adsorption obtained by isothermal titration calorimetry were 8.03 and 6.94 kJ mol-1. Regeneration and reuse of SBST were investigated and the best conditions applied for fixed-bed column adsorption in five consecutive cycles. SBST was fully desorbed and Qmax values for Co2+ (0.95 mmol g-1) and Ni2+ (1.02 mmol g-1) were estimated using the Bohart-Adams model.

Synthesis and application of sugarcane bagasse cellulose mixed esters. Part I: Removal of Co2+ and Ni2+ from single spiked aqueous solutions in batch mode using sugarcane bagasse cellulose succinate phthalate.

Sugarcane bagasse cellulose mixed ester succinate phthalate (SBSPh) was synthesized by a novel one-pot reaction method. The effects of temperature, time and mole fraction of succinic anhydride (χSA) on the responses weight gain (wg), number of carboxylic acid groups (nT,COOH), and adsorption capacity (q) of Co2+ and Ni2+ were evaluated by a 23 experimental design. The chemical structure of the material was elucidated by Fourier transform infrared, 13C Multiple Cross-Polarization solid-state NMR spectroscopy and 1H NMR relaxometry. The best SBSPh synthesis condition (100 °C, 11 h, χSA of 0.2) yielded a wg of 59.1%, nT,COOH of 3.41 mmol g-1, and values of qCo2+ and qNi2+ of 0.348 and 0.346 mmol g-1, respectively. The Sips model fitted better the equilibrium data, and the maximum adsorption capacities (pH 5.75 and 25 °C) estimated by this model were 0.62 and 0.53 mmol g-1 for Co2+ and Ni2+, respectively. The ΔadsH° values estimated by isothermal titration calorimetry were 8.43 and 7.79 kJ mol-1 for Co2+ and Ni2+, respectively. Desorption and re-adsorption efficiencies were evaluated by a 22 experimental design, which showed that SBSPh adsorbent can be recovered and reused without significant loss of adsorption capacity.

Ensembl 2019.

The Ensembl project (https://www.ensembl.org) makes key genomic data sets available to the entire scientific community without restrictions. Ensembl seeks to be a fundamental resource driving scientific progress by creating, maintaining and updating reference genome annotation and comparative genomics resources. This year we describe our new and expanded gene, variant and comparative annotation capabilities, which led to a 50% increase in the number of vertebrate genomes we support. We have also doubled the number of available human variants and added regulatory regions for many mouse cell types and developmental stages. Our data sets and tools are available via the Ensembl website as well as a through a RESTful webservice, Perl application programming interface and as data files for download.

Ensembl variation resources.

The major goal of sequencing humans and many other species is to understand the link between genomic variation, phenotype and disease. There are numerous valuable and well-established variation resources, but collating and making sense of non-homogeneous, often large-scale data sets from disparate sources remains a challenge. Without a systematic catalogue of these data and appropriate query and annotation tools, understanding the genome sequence of an individual and assessing their disease risk is impossible. In Ensembl, we substantially solve this problem: we develop methods to facilitate data integration and broad access; aggregate information in a consistent manner and make it available a variety of standard formats, both visually and programmatically; build analysis pipelines to compare variants to comprehensive genomic annotation sets; and make all tools and data publicly available.

Bifunctionalized chitosan: A versatile adsorbent for removal of Cu(II) and Cr(VI) from aqueous solution.

This study describes the chemical modification of chitosan to produce a novel bifunctionalized adsorbent material (C4) for the removal of Cu2+ and oxyanions of Cr6+ from a single aqueous solution. The chemical modifications allowed C4 to be insoluble under acidic conditions, improving the chemical properties of the modified chitosan in aqueous solution. C4 adsorbent was synthesized by reaction of the amino group of chitosan with 2-pyridinecarboxaldehyde, a reduction of imine group, followed by esterification with EDTA dianhydride (EDTAD). C4 was characterized by solid-state 13C nuclear magnetic resonance, infrared spectroscopy, and elemental analysis. The adsorption studies of Cu2+ and oxyanions of Cr6+ in a batch mode were evaluated as a function of the contact time (kinetics), solution pH, and initial metal ion concentration. The maximum adsorption capacities (Qmax) of C4 for the adsorption of Cu2+ (pH 5.5) and Cr6+ (pH 2.0) were 2.60 and 3.50 mmol/g, respectively. The reusability of the recovered C4 adsorbent was also evaluated.

Modeling adsorption of copper(II), cobalt(II) and nickel(II) metal ions from aqueous solution onto a new carboxylated sugarcane bagasse. Part II: Optimization of monocomponent fixed-bed column adsorption.

In the second part of this series of studies, the monocomponent adsorption of Cu2+, Co2+ and Ni2+ onto STA adsorbent in a fixed-bed column was investigated and optimized using a 22 central composite design. The process variables studied were: initial metal ion concentration and spatial time, and the optimized responses were: adsorption capacity of the bed (Qmax), efficiency of the adsorption process (EAP), and effective use of the bed (H). The higher Qmax for Cu2+, Co2+ and Ni2+ were 1.060, 0.800 and 1.029 mmol/g, respectively. The breakthrough curves were modeled by the original Thomas and Bohart-Adams models. The changes in enthalpy (ΔadsH°) of adsorption of the metal ions onto STA were determined by isothermal titration calorimetry (ITC). The values of ΔadsH° were in the range of 3.0-6.8 kJ/mol, suggesting that the adsorption process involved physisorption. Desorption (Edes) and re-adsorption (Ere-ads) of metal ions from the STA adsorbent were also investigated in batch mode, and the optimum conditions were applied for three cycles of adsorption/desorption in a fixed bed column. For these cycles, the lowest values of Edes and Ere-ads were 95 and 92.3%, respectively, showing that STA is a promising candidate for real applications on a large scale.

Trimellitated sugarcane bagasse: A versatile adsorbent for removal of cationic dyes from aqueous solution. Part I: Batch adsorption in a monocomponent system.

Trimellitated-sugarcane bagasse (STA) was used as an environmentally friendly adsorbent for removal of the basic dyes auramine-O (AO) and safranin-T (ST) from aqueous solutions at pH 4.5 and 7.0. Dye adsorption was evaluated as a function of STA dosage, agitation speed, solution pH, contact time, and initial dye concentration. Pseudo-first- and pseudo-second-order, Elovich, intraparticle diffusion, and Boyd models were used to model adsorption kinetics. Langmuir, Dubinin-Radushkevich, Redlich-Peterson, Sips, Hill-de Boer, and Fowler-Guggenheim models were used to model adsorption isotherms, while a Scatchard plot was used to evaluate the existence of different adsorption sites. Maximum adsorption capacities for removal of AO and ST were 1.005 and 0.638 mmol g-1 at pH 4.5, and 1.734 and 1.230 mmol g-1 at pH 7.0, respectively. Adsorption enthalpy changes obtained by isothermal titration calorimetry (ITC) ranged from -21.07 ±â€¯0.25 to -7.19 ±â€¯0.05 kJ mol-1, indicating that both dyes interacted with STA by physisorption. Dye desorption efficiencies ranged from 41 to 51%, and re-adsorption efficiencies ranged from 66 to 87%, showing that STA can be reused in new adsorption cycles. ITC data combined with isotherm studies allowed clarification of adsorption interactions.

Synthesis and application of a new carboxylated cellulose derivative. Part III: Removal of auramine-O and safranin-T from mono- and bi-component spiked aqueous solutions.

In the third part of this series of studies, the adsorption of the basic textile dyes auramine-O (AO) and safranin-T (ST) on a carboxylated cellulose derivative (CTA) were evaluated in mono- and bi-component spiked aqueous solutions. Adsorption studies were developed as a function of solution pH, contact time, and initial dye concentration. Adsorption kinetic data were modeled by monocomponent kinetic models of pseudo-first- (PFO), pseudo-second-order (PSO), intraparticle diffusion, and Boyd, while the competitive kinetic model of Corsel was used to model bicomponent kinetic data. Monocomponent adsorption equilibrium data were modeled by the Langmuir, Sips, Fowler-Guggenhein, Hill de-Boer, and Konda models, while the IAST and RAST models were used to model bicomponent equilibrium data. Monocomponent maximum adsorption capacities for AO and ST at pH 4.5 were 2.841 and 3.691 mmol g-1, and at pH 7.0 were 5.443 and 4.074 mmol g-1, respectively. Bicomponent maximum adsorption capacities for AO and ST at pH 7.0 were 1.230 and 3.728 mmol g-1. Adsorption enthalpy changes (ΔadsH) were obtained using isothermal titration calorimetry. The values of ΔadsH ranged from -18.83 to -5.60 kJ mol-1, suggesting that physisorption controlled the adsorption process. Desorption and re-adsorption of CTA was also evaluated.

Synthesis, characterisation and application of pyridine-modified chitosan derivatives for the first non-racemic Cu-catalysed Henry reaction.

The preparation, characterisation and application of two pyridine-modified chitosan derivatives (C1 and C2) containing Cu(OAc)2 adsorbed as catalysts for the conversion of benzaldehyde into 2-nitro-1-phenylethanol are described. Quantitative solid-state 13C multiple-contact cross-polarization, magic-angle-spinning, nuclear magnetic resonance (MC-CP MAS NMR) measurements confirmed the successful grafting of 2-pyridinecarboxaldehyde and 6-methylpyridine-2-carboxaldehyde to the chitosan backbone and indicated that 47(±2)% of the NH2 groups were grafted for both C1 and C2. The use of C1-Cu(OAc)2 as a catalyst in the nitroaldol reaction led to 96(±1)% conversion and 19(±4)% enantiomeric excess (ee), while the use of C2-Cu(OAc)2 as a catalyst also promoted the nitroaldol reaction, affording almost quantitatively the expected 2-nitro-1-phenylethanol (98(±1)%) with 14.5(±1.5)% ee.

Ensembl 2018.

The Ensembl project has been aggregating, processing, integrating and redistributing genomic datasets since the initial releases of the draft human genome, with the aim of accelerating genomics research through rapid open distribution of public data. Large amounts of raw data are thus transformed into knowledge, which is made available via a multitude of channels, in particular our browser (http://www.ensembl.org). Over time, we have expanded in multiple directions. First, our resources describe multiple fields of genomics, in particular gene annotation, comparative genomics, genetics and epigenomics. Second, we cover a growing number of genome assemblies; Ensembl Release 90 contains exactly 100. Third, our databases feed simultaneously into an array of services designed around different use cases, ranging from quick browsing to genome-wide bioinformatic analysis. We present here the latest developments of the Ensembl project, with a focus on managing an increasing number of assemblies, supporting efforts in genome interpretation and improving our browser.

Optimization of cellulose and sugarcane bagasse oxidation: Application for adsorptive removal of crystal violet and auramine-O from aqueous solution.

Cellulose (Cel) and sugarcane bagasse (SB) were oxidized with an H3PO4-NaNO2 mixture to obtain adsorbent materials with high contents of carboxylic groups. The oxidation reactions of Cel and SB were optimized using design of experiments (DOE) and response surface methodology (RSM). The optimized synthesis conditions yielded Cox and SBox with 4.8mmol/g and 4.5mmol/g of carboxylic acid groups, respectively. Cox and SBox were characterized by FTIR, TGA, PZC and solid-state 13C NMR. The adsorption of the model cationic dyes crystal violet (CV) and auramine-O (AO) on Cox and SBox in aqueous solution was investigated as a function of the solution pH, the contact time and the initial dye concentration. The adsorption of CV and AO on Cox was described by the Elovich equation and the pseudo-first-order kinetic model respectively, while the adsorption of CV and AO on SBox was described by the pseudo-second-order kinetic model. Adsorption isotherms were well fitted by the Langmuir and Konda models, with maximum adsorption capacities (Qmax) of 1117.8mg/g of CV and 1223.3mg/g of AO on Cox and 1018.2mg/g of CV and 682.8mg/g of AO on SBox. Desorption efficiencies were in the range of 50-52% and re-adsorption capacities varied from 65 to 81%, showing the possibility of reuse of both adsorbent materials.