High-depth African genomes inform human migration and health.

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals-comprising 50 ethnolinguistic groups, including previously unsampled populations-to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon-but in other genes, variants denoted as 'likely pathogenic' in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health.

SysBiolPGWAS: simplifying post-GWAS analysis through the use of computational technologies and integration of diverse omics datasets.

MOTIVATION: Post-genome-wide association studies (pGWAS) analysis is designed to decipher the functional consequences of significant single-nucleotide polymorphisms (SNPs) in the era of GWAS. This can be translated into research insights and clinical benefits such as the effectiveness of strategies for disease screening, treatment and prevention. However, the setup of pGWAS (pGWAS) tools can be quite complicated, and it mostly requires big data. The challenge however is, scientists are required to have sufficient experience with several of these technically complex and complicated tools in order to complete the pGWAS analysis. RESULTS: We present SysBiolPGWAS, a pGWAS web application that provides a comprehensive functionality for biologists and non-bioinformaticians to conduct several pGWAS analyses to overcome the above challenges. It provides unique functionalities for analysis involving multi-omics datasets and visualization using various bioinformatics tools. SysBiolPGWAS provides access to individual pGWAS tools and a novel custom pGWAS pipeline that integrates several individual pGWAS tools and data. The SysBiolPGWAS app was developed to be a one-stop shop for pGWAS analysis. It targets researchers in the area of the human genome and performs its analysis mainly in the autosomal chromosomes. AVAILABILITY AND IMPLEMENTATION: SysBiolPGWAS web app was developed using JavaScript/TypeScript web frameworks and is available at: https://spgwas.waslitbre.org/. All codes are available in this GitHub repository https://github.com/covenant-university-bioinformatics.

Chemistry and Pharmacological diversity of Benzothiazepine - Excellent pathway to drug discovery.

In this era of sporadic advancement in science and technology, a substantial amount of intervention is being set in motion to reduce health-related diseases. Discoveries from researchers have pinpointed the usefulness of heterocyclic compounds, amongst which benzothiazepine (BTZ) derivatives have been synthesized for their various pharmacological activities. This also contributes to their undeniable application in therapeutic medicine for the development of efficacious drugs. BTZs are compounds with a benzene ring fused with a thiazepine ring. This work contains several methods that have been used to synthesize 1,3-, 1,4-, 1,5-, and 4-1-benzothiazepine derivatives. In addition, up-to-date information about the crucial pharmacological activities of BTZ derivatives has been reviewed in this present study to appreciate their druggable potential in therapeutic medicine for drug development. Drug design and development have further been simplified with the implementation of computer aided approaches to predict biological interactions which can help in the design of several derivatives. Hence, the structural activity relationship (SAR), ADMET and the molecular docking studies of BTZ derivatives were discussed to further establish their interactions and safety in biological systems. This present work aims to expound on the reported chemistry and pharmacological propensity of BTZ moiety in relation to other relevant moieties to validate their potential as excellent pharmacophores in drug design and development.

Plant genomics in Africa: present and prospects.

Plants are the world's most consumed goods. They are of high economic value and bring many health benefits. In most countries in Africa, the supply and quality of food will rise to meet the growing population's increasing demand. Genomics and other biotechnology tools offer the opportunity to improve subsistence crops and medicinal herbs in the continent. Significant advances have been made in plant genomics, which have enhanced our knowledge of the molecular processes underlying both plant quality and yield. The sequencing of complex genomes of African plant species, facilitated by the continuously evolving next-generation sequencing technologies and advanced bioinformatics approaches, has provided new opportunities for crop improvement. This review summarizes the achievements of genome sequencing projects of endemic African plants in the last two decades. We also present perspectives and challenges for future plant genomic studies that will accelerate important plant breeding programs for African communities. These challenges include a lack of basic facilities, a lack of sequencing and bioinformatics facilities, and a lack of skills to design genomics studies. However, it is imperative to state that African countries have become key players in the plant genome revolution and genome derived-biotechnology. Therefore, African governments should invest in public plant genomics research and applications, establish bioinformatics platforms and training programs, and stimulate university and industry partnerships to fully deploy plant genomics, particularly in the fields of agriculture and medicine.

H3ABioNet, a sustainable pan-African bioinformatics network for human heredity and health in Africa.

The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants, and microbiota occurs in Africa, yet genomic research outputs from the continent are limited. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive the development of genomic research for human health in Africa, and through recognition of the critical role of bioinformatics in this process, spurred the establishment of H3ABioNet, a pan-African bioinformatics network for H3Africa. The limitations in bioinformatics capacity on the continent have been a major contributory factor to the lack of notable outputs in high-throughput biology research. Although pockets of high-quality bioinformatics teams have existed previously, the majority of research institutions lack experienced faculty who can train and supervise bioinformatics students. H3ABioNet aims to address this dire need, specifically in the area of human genetics and genomics, but knock-on effects are ensuring this extends to other areas of bioinformatics. Here, we describe the emergence of genomics research and the development of bioinformatics in Africa through H3ABioNet.

Assessing computational genomics skills: Our experience in the H3ABioNet African bioinformatics network.

The H3ABioNet pan-African bioinformatics network, which is funded to support the Human Heredity and Health in Africa (H3Africa) program, has developed node-assessment exercises to gauge the ability of its participating research and service groups to analyze typical genome-wide datasets being generated by H3Africa research groups. We describe a framework for the assessment of computational genomics analysis skills, which includes standard operating procedures, training and test datasets, and a process for administering the exercise. We present the experiences of 3 research groups that have taken the exercise and the impact on their ability to manage complex projects. Finally, we discuss the reasons why many H3ABioNet nodes have declined so far to participate and potential strategies to encourage them to do so.

Bioinformatics education--perspectives and challenges out of Africa.

The discipline of bioinformatics has developed rapidly since the complete sequencing of the first genomes in the 1990s. The development of many high-throughput techniques during the last decades has ensured that bioinformatics has grown into a discipline that overlaps with, and is required for, the modern practice of virtually every field in the life sciences. This has placed a scientific premium on the availability of skilled bioinformaticians, a qualification that is extremely scarce on the African continent. The reasons for this are numerous, although the absence of a skilled bioinformatician at academic institutions to initiate a training process and build sustained capacity seems to be a common African shortcoming. This dearth of bioinformatics expertise has had a knock-on effect on the establishment of many modern high-throughput projects at African institutes, including the comprehensive and systematic analysis of genomes from African populations, which are among the most genetically diverse anywhere on the planet. Recent funding initiatives from the National Institutes of Health and the Wellcome Trust are aimed at ameliorating this shortcoming. In this paper, we discuss the problems that have limited the establishment of the bioinformatics field in Africa, as well as propose specific actions that will help with the education and training of bioinformaticians on the continent. This is an absolute requirement in anticipation of a boom in high-throughput approaches to human health issues unique to data from African populations.

Computational biology and bioinformatics in Nigeria.

Over the past few decades, major advances in the field of molecular biology, coupled with advances in genomic technologies, have led to an explosive growth in the biological data generated by the scientific community. The critical need to process and analyze such a deluge of data and turn it into useful knowledge has caused bioinformatics to gain prominence and importance. Bioinformatics is an interdisciplinary research area that applies techniques, methodologies, and tools in computer and information science to solve biological problems. In Nigeria, bioinformatics has recently played a vital role in the advancement of biological sciences. As a developing country, the importance of bioinformatics is rapidly gaining acceptance, and bioinformatics groups comprised of biologists, computer scientists, and computer engineers are being constituted at Nigerian universities and research institutes. In this article, we present an overview of bioinformatics education and research in Nigeria. We also discuss professional societies and academic and research institutions that play central roles in advancing the discipline in Nigeria. Finally, we propose strategies that can bolster bioinformatics education and support from policy makers in Nigeria, with potential positive implications for other developing countries.

Computational Studies on 6-Pyruvoyl Tetrahydropterin Synthase (6-PTPS) of Plasmodium falciparum.

6-Pyruvoyl tetrahydropterin synthase (6-PTPS) is a lyase involved in the synthesis of tetrahydrobiopterin. In Plasmodium species where dihydroneopterin aldolase (DHNA) is absent, it acts in the folate biosynthetic pathway necessary for the growth and survival of the parasite. The 6-pyruvoyl tetrahydropterin synthase of Plasmodium falciparum (PfPTPS) has been identified as a potential antimalarial drug target. This study identified potential inhibitors of PfPTPS using molecular docking techniques. Molecular docking and virtual screening of 62 compounds including the control to the deposited Protein Data Bank (PDB) structure was carried out using AutoDock Vina in PyRx. Five of the compounds, N,N-dimethyl-N'-[4-oxo-6-(2,2,5-trimethyl-1,3-dioxolan-4-yl)-3H-pteridin-2-yl]methanimidamide (140296439), 2-amino-6-[(1R)-3-cyclohexyl-1-hydroxypropyl]-3H-pteridin-4-one (140296495), 2-(2,3-dihydroxypropyl)-8,9-dihydro-6H-pyrimido[2,1-b]pteridine-7,11-dione (144380406), 2-(dimethylamino)-6-[(2,2-dimethyl-1,3-dioxolan-4-yl)-hydroxymethyl]-3H-pteridin-4-one (135573878), and [1-acetyloxy-1-(2-methyl-4-oxo-3H-pteridin-6-yl)propan-2-yl] acetate (136075207), showed better binding affinity than the control ligand, biopterin (135449517), and were selected and screened. Three conformers of 140296439 with the binding energy of -7.2, -7.1, and -7.0 kcal/mol along with 140296495 were better than the control at -5.7 kcal/mol. In silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies predicted good pharmacokinetic properties of all the compounds while reporting a high risk of irritant toxicity in 140296439 and 144380406. The study highlights the five compounds, 140296439, 140296495, 144380406, 135573878 and 136075207, as potential inhibitors of PfPTPS and possible compounds for antimalarial drug development.

Correction: Heuristic-enabled active machine learning: A case study of predicting essential developmental stage and immune response genes in Drosophila melanogaster.

[This corrects the article DOI: 10.1371/journal.pone.0288023.].

In Silico Design of Potential Small-Molecule Antibiotic Adjuvants against Salmonella typhimurium Ortho Acetyl Sulphydrylase Synthase to Address Antimicrobial Resistance.

The inhibition of O-acetyl sulphydrylase synthase isoforms has been reported to represent a promising approach for the development of antibiotic adjuvants. This occurs via the organism developing an unpaired oxidative stress response, causing a reduction in antibiotic resistance in vegetative and swarm cell populations. This consequently increases the effectiveness of conventional antibiotics at lower doses. This study aimed to predict potential inhibitors of Salmonella typhimurium ortho acetyl sulphydrylase synthase (StOASS), which has lower binding energy than the cocrystalized ligand pyridoxal 5 phosphate (PLP), using a computer-aided drug design approach including pharmacophore modeling, virtual screening, and in silico ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) evaluation. The screening and molecular docking of 4254 compounds obtained from the PubChem database were carried out using AutoDock vina, while a post-screening analysis was carried out using Discovery Studio. The best three hits were compounds with the PubChem IDs 118614633, 135715279, and 155773276, possessing binding affinities of -9.1, -8.9, and -8.8 kcal/mol, respectively. The in silico ADMET prediction showed that the pharmacokinetic properties of the best hits were relatively good. The optimization of the best three hits via scaffold hopping gave rise to 187 compounds, and they were docked against StOASS; this revealed that lead compound 1 had the lowest binding energy (-9.3 kcal/mol) and performed better than its parent compound 155773276. Lead compound 1, with the best binding affinity, has a hydroxyl group in its structure and a change in the core heterocycle of its parent compound to benzimidazole, and pyrimidine introduces a synergistic effect and consequently increases the binding energy. The stability of the best hit and optimized compound at the StOASS active site was determined using RMSD, RMSF, radius of gyration, and SASA plots generated from a molecular dynamics simulation. The MD simulation results were also used to monitor how the introduction of new functional groups of optimized compounds contributes to the stability of ligands at the target active site. The improved binding affinity of these compounds compared to PLP and their toxicity profile, which is predicted to be mild, highlights them as good inhibitors of StOASS, and hence, possible antimicrobial adjuvants.

Structure-based design, and development of amidinyl, amidoximyl and hydroxamic acid based organic molecules as novel antimalarial drug candidates.

Malaria remains a significant global health concern causing numerous fatalities and the emergence of antimalarial drug resistance highlights the urgent need for novel therapeutic options with innovative mechanisms of action and targets. This study aimed to design potential inhibitors of Plasmodium falciparum 6-pyruvoyltetrahydropterin synthase (PfPTPS), synthesize them, and experimentally validate their efficacy as antimalarial agents. A structure-based approach was employed to design a series of novel derivatives, including amidinyl, amidoximyl and hydroxamic acid analogs (1c, 1d, 2b, and 3b), with a focus on their ability to bind to the Zn2+ present in the active site of PfPTPS. The syntheses of these compounds were accomplished through various multi-step synthetic pathways and their structural identities were confirmed using 1H and 13C NMR spectra, mass spectra, and elemental analysis. The compounds were screened for their antiplasmodial activity against the NF54 strain of P. falciparum and in vitro cytotoxicity testing was performed using L-6 cells. The in vivo acute toxicity of the compounds was evaluated in mice. Docking studies of the compounds with the 3D structure of PfPTPS revealed their strong binding affinities, with compound 3b exhibiting notable metal-acceptor interaction with the Zn2+ in the protein binding pocket thereby positioning it as a lead compound for PfPTPS inhibition. The in vitro antiplasmodial studies revealed moderate efficacies against the Pf NF54 strain, particularly compounds 1d and 3b which displayed IC50 < 0.2 µM. No significant cytotoxicity was noted on the L-6 rat cell line. Moreover, in vivo studies suggested that compound 3b exhibited both safety and efficacy in treating rodent malaria. The identified lead compound in this study represents a possible candidate for antimalarial drug development and can be further explored in the search for alternative antifolate drugs to combat the malaria menace.

Personalizing medicine in Africa: current state, progress and challenges.

Personalized medicine has been identified as a powerful tool for addressing the myriad of health issues facing different health systems globally. Although recent studies have expanded our understanding of how different factors such as genetics and the environment play significant roles in affecting the health of individuals, there are still several other issues affecting their translation into personalizing health interventions globally. Since African populations have demonstrated huge genetic diversity, there is a significant need to apply the concepts of personalized medicine to overcome various African-specific health challenges. Thus, we review the current state, progress, and challenges facing the adoption of personalized medicine in Africa with a view to providing insights to critical stakeholders on the right approach to deploy.

Pharmacophore-Aided Virtual Screening and Molecular Dynamics Simulation Identifies TrkB Agonists for Treatment of CDKL5-Deficiency Disorders.

Therapeutic intervention in cyclin-dependent kinase-like 5 (CDKL5) deficiency disorders (CDDs) has remained a concern over the years. Recent advances into the mechanistic interplay of signalling pathways has revealed the role of deficient tropomyosin receptor kinase B (TrkB)/phospholipase C γ1 signalling cascade in CDD. Novel findings showed that in vivo administration of a TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), resulted in a remarkable reversal in the molecular pathologic mechanisms underlying CDD. Owing to this discovery, this study aimed to identify more potent TrkB agonists than 7,8-DHF that could serve as alternatives or combinatorial drugs towards effective management of CDD. Using pharmacophore modelling and multiple database screening, we identified 691 compounds with identical pharmacophore features with 7,8-DHF. Virtual screening of these ligands resulted in identification of at least 6 compounds with better binding affinities than 7,8-DHF. The in silico pharmacokinetic and ADMET studies of the compounds also indicated better drug-like qualities than those of 7,8-DHF. Postdocking analyses and molecular dynamics simulations of the best hits, 6-hydroxy-10-(2-oxo-1-azatricyclo[7.3.1.05,13]trideca-3,5(13),6,8-tetraen-3-yl)-8-oxa-13,14,16-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1,3,6,9,11,15-hexaen-5-one (PubChem: 91637738) and 6-hydroxy-10-(8-methyl-2-oxo-1H-quinolin-3-yl)-8-oxa-13,14,16-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1,3,6,9,11,15-hexaen-5-one (PubChem ID: 91641310), revealed unique ligand interactions, validating the docking findings. We hereby recommend experimental validation of the best hits in CDKL5 knock out models before consideration as drugs in CDD management.

Mathematical modeling of malaria transmission dynamics in humans with mobility and control states.

Malaria importation is one of the hypothetical drivers of malaria transmission dynamics across the globe. Several studies on malaria importation focused on the effect of the use of conventional malaria control strategies as approved by the World Health Organization (WHO) on malaria transmission dynamics but did not capture the effect of the use of traditional malaria control strategies by vigilant humans. In order to handle the aforementioned situation, a novel system of Ordinary Differential Equations (ODEs) was developed comprising the human and the malaria vector compartments. Analysis of the system was carried out to assess its quantitative properties. The novel computational algorithm used to solve the developed system of ODEs was implemented and benchmarked with the existing Runge-Kutta numerical solution method. Furthermore, simulations of different vigilant conditions useful to control malaria were carried out. The novel system of malaria models was well-posed and epidemiologically meaningful based on its quantitative properties. The novel algorithm performed relatively better in terms of model simulation accuracy than Runge-Kutta. At the best model-fit condition of 98% vigilance to the use of conventional and traditional malaria control strategies, this study revealed that malaria importation has a persistent impact on malaria transmission dynamics. In lieu of this, this study opined that total vigilance to the use of the WHO-approved and traditional malaria management tools would be the most effective control strategy against malaria importation.

Heuristic-enabled active machine learning: A case study of predicting essential developmental stage and immune response genes in Drosophila melanogaster.

Computational prediction of absolute essential genes using machine learning has gained wide attention in recent years. However, essential genes are mostly conditional and not absolute. Experimental techniques provide a reliable approach of identifying conditionally essential genes; however, experimental methods are laborious, time and resource consuming, hence computational techniques have been used to complement the experimental methods. Computational techniques such as supervised machine learning, or flux balance analysis are grossly limited due to the unavailability of required data for training the model or simulating the conditions for gene essentiality. This study developed a heuristic-enabled active machine learning method based on a light gradient boosting model to predict essential immune response and embryonic developmental genes in Drosophila melanogaster. We proposed a new sampling selection technique and introduced a heuristic function which replaces the human component in traditional active learning models. The heuristic function dynamically selects the unlabelled samples to improve the performance of the classifier in the next iteration. Testing the proposed model with four benchmark datasets, the proposed model showed superior performance when compared to traditional active learning models (random sampling and uncertainty sampling). Applying the model to identify conditionally essential genes, four novel essential immune response genes and a list of 48 novel genes that are essential in embryonic developmental condition were identified. We performed functional enrichment analysis of the predicted genes to elucidate their biological processes and the result evidence our predictions. Immune response and embryonic development related processes were significantly enriched in the essential immune response and embryonic developmental genes, respectively. Finally, we propose the predicted essential genes for future experimental studies and use of the developed tool accessible at http://heal.covenantuniversity.edu.ng for conditional essentiality predictions.

In silico Structure Prediction, Molecular Docking, and Dynamic Simulation of Plasmodium falciparum AP2-I Transcription Factor.

Plasmodium falciparum Apicomplexan Apetala 2 Invasion (PfAP2-I) transcription factor (TF) is a protein that regulates the expression of a subset of gene families involved in P. falciparum red blood cell (RBC) invasion. Inhibiting PfAP2-I TF with small molecules represents a potential new antimalarial therapeutic target to combat drug resistance, which this study aims to achieve. The 3D model structure of PfAP2-I was predicted ab initio using ROBETTA prediction tool and was validated using Save server 6.0 and MolProbity. Computed Atlas of Surface Topography of proteins (CASTp) 3.0 was used to predict the active sites of the PfAP2-I modeled structure. Pharmacophore modeling of the control ligand and PfAP2-I modeled structure was carried out using the Pharmit server to obtain several compounds used for molecular docking analysis. Molecular docking and postdocking studies were conducted using AutoDock vina and Discovery studio. The designed ligands' toxicity predictions and in silico drug-likeness were performed using the SwissADME predictor and OSIRIS Property Explorer. The modeled protein structure from the ROBETTA showed a validation result of 96.827 for ERRAT, 90.2% of the amino acid residues in the most favored region for the Ramachandran plot, and MolProbity score of 1.30 in the 98th percentile. Five (5) best hit compounds from molecular docking analysis were selected based on their binding affinity (between -8.9 and -11.7 Kcal/mol) to the active site of PfAP2-I and were considered for postdocking studies. For the absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties, compound MCULE-7146940834 had the highest drug score (0.63) and drug-likeness (6.76). MCULE-7146940834 maintained a stable conformation within the flexible protein's active site during simulation. The good, estimated binding energies, drug-likeness, drug score, and molecular dynamics simulation interaction observed for MCULE-7146940834 against PfAP2-I show that MCULE-7146940834 can be considered a lead candidate for PfAP2-I inhibition. Experimental validations should be carried out to ascertain the efficacy of these predicted best hit compounds.

Synthesis, in silico and in vitro antimicrobial efficacy of substituted arylidene-based quinazolin-4(3H)-one motifs.

Introduction: Quinazolin-4(3H)-one derivatives have attracted considerable attention in the pharmacological profiling of therapeutic drug targets. The present article reveals the development of arylidene-based quinazolin-4(3H)-one motifs as potential antimicrobial drug candidates. Methods: The synthetic pathway was initiated through thermal cyclization of acetic anhydride on anthranilic acid to produce 2-methyl-4H-3,1-benzoxazan-4-one 1, which (upon condensation with hydrazine hydrate) gave 3-amino-2-methylquinazolin-4(3H)-one 2. The reaction of intermediate 2 at its amino side arm with various benzaldehyde derivatives furnished the final products, in the form of substituted benzylidene-based quinazolin-4(3H)-one motifs 3a-l, and with thiophene-2-carbaldehyde to afford 3 m. The purified targeted products 3a-m were effectively characterized for structural authentication using physicochemical parameters, microanalytical data, and spectroscopic methods, including IR, UV, and 1H- and 13C-NMR, as well as mass spectral data. The substituted arylidene-based quinazolin-4(3H)-one motifs 3a-m were screened for both in silico and in vitro antimicrobial properties against selected bacteria and fungi. The in silico studies carried out consisted of predicted ADMET screening, molecular docking, and molecular dynamics (MD) simulation studies. Furthermore, in vitro experimental validation was performed using the agar diffusion method, and the standard antibacterial and antifungal drugs used were gentamicin and ketoconazole, respectively. Results and discussion: Most of the compounds possessed good binding affinities according to the molecular docking studies, while MD simulation revealed their levels of structural stability in the protein-ligand complexes. 2-methyl-3-((thiophen-2-ylmethylene)amino) quinazolin-4(3H)-one 3 m emerged as both the most active antibacterial agent (with an minimum inhibitory concentration (MIC) value of 1.95 µg/mL) against Staphylococcus aureus and the most active antifungal agent (with an MIC value of 3.90 µg/mL) against Candida albicans, Aspergillus niger, and Rhizopus nigricans.

A deep population reference panel of tandem repeat variation.

Tandem repeats (TRs) represent one of the largest sources of genetic variation in humans and are implicated in a range of phenotypes. Here we present a deep characterization of TR variation based on high coverage whole genome sequencing from 3,550 diverse individuals from the 1000 Genomes Project and H3Africa cohorts. We develop a method, EnsembleTR, to integrate genotypes from four separate methods resulting in high-quality genotypes at more than 1.7 million TR loci. Our catalog reveals novel sequence features influencing TR heterozygosity, identifies population-specific trinucleotide expansions, and finds hundreds of novel eQTL signals. Finally, we generate a phased haplotype panel which can be used to impute most TRs from nearby single nucleotide polymorphisms (SNPs) with high accuracy. Overall, the TR genotypes and reference haplotype panel generated here will serve as valuable resources for future genome-wide and population-wide studies of TRs and their role in human phenotypes.