Baobab Index

Sickle cell disease (SCD) is one of the most common monogenic diseases in humans with multiple phenotypic expressions that can manifest as both acute and chronic complications. Although described more than a century ago, challenges in comprehensive disease management and collaborative research on this disease are compounded by the complex molecular and clinical phenotypes of SCD, environmental and psychosocial factors, limited therapeutic options and ambiguous terminology. This ambiguous terminology has hampered the integration and interoperability of existing SCD knowledge, and SCD research translation. The SCD Ontology (SCDO), which is a community-driven integrative and universal knowledge representation system for SCD, overcomes this issue by providing a controlled vocabulary developed by a group of experts in both SCD and ontology design. SCDO is the first and most comprehensive standardized human- and machine-readable resource that unambiguously represents terminology and concepts about SCD for researchers, patients and clinicians. It is built around the central concept 'hemoglobinopathy', allowing inclusion of non-SCD haemoglobinopathies, such as thalassaemias, which may interfere with or influence SCD phenotypic manifestations. This collaboratively developed ontology constitutes a comprehensive knowledge management system and standardized terminology of various SCD-related factors. The SCDO will promote interoperability of different research datasets, facilitate seamless data sharing and collaborations, including meta-analyses within the SCD community, and support the development and curation of data-basing and clinical informatics in SCD.

The sensitivity of tropical forest carbon to climate is a key uncertainty in predicting global climate change. Although short-term drying and warming are known to affect forests, it is unknown if such effects translate into long-term responses. Here, we analyze 590 permanent plots measured across the tropics to derive the equilibrium climate controls on forest carbon. Maximum temperature is the most important predictor of aboveground biomass (-9.1 megagrams of carbon per hectare per degree Celsius), primarily by reducing woody productivity, and has a greater impact per °C in the hottest forests (>32.2°C). Our results nevertheless reveal greater thermal resilience than observations of short-term variation imply. To realize the long-term climate adaptation potential of tropical forests requires both protecting them and stabilizing Earth's climate.

The spread of Plasmodium falciparum isolates carrying mutations in the kelch13 (Pfkelch13) gene associated with artemisinin resistance (PfART-R) in southeast Asia threatens malaria control and elimination efforts. Emergence of PfART-R in Africa would result in a major public health problem. In this systematic review, we investigate the frequency and spatial distribution of Pfkelch13 mutants in Africa, including mutants linked to PfART-R in southeast Asia. Seven databases were searched (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline, and Web of Science) for relevant articles about polymorphisms of the Pfkelch13 gene in Africa before January, 2019. Following PRISMA guidelines, 53 studies that sequenced the Pfkelch13 gene of 23 100 sample isolates in 41 sub-Saharan African countries were included. The Pfkelch13 sequence was highly polymorphic (292 alleles, including 255 in the Pfkelch13-propeller domain) but with mutations occurring at very low relative frequencies. Non-synonymous mutations were found in only 626 isolates (2·7%) from west, central, and east Africa. According to WHO, nine different mutations linked to PfART-R in southeast Asia (Phe446Ile, Cys469Tyr, Met476Ile, Arg515Lys, Ser522Cys, Pro553Leu, Val568Gly, Pro574Leu, and Ala675Val) were detected, mainly in east Africa. Several other Pfkelch13 mutations, such as those structurally similar to southeast Asia PfART-R mutations, were also identified, but their relevance for drug resistance is still unknown. This systematic review shows that Africa, thought to not have established PfART-R, reported resistance-related mutants in the past 5 years. Surveillance using PfART-R molecular markers can provide valuable decision-making information to sustain the effectiveness of artemisinin in Africa.

Many cultivated coffee varieties descend from Coffea canephora, commonly known as Robusta coffee. The Congo Basin has a century-long history of Robusta coffee cultivation and breeding, and is hypothesized to be the region of origin of many of the cultivated Robusta varieties. Since little is known about the genetic composition of C. canephora in this region, we assessed the genetic diversity of wild and cultivated C. canephora shrubs in the Democratic Republic of the Congo. Using 18 microsatellite markers, we studied the genetic composition of wild and backyard-grown C. canephora shrubs in the Tshopo and Ituri provinces and multiple accessions from the INERA Yangambi Coffee Collection. We assessed genetic clustering patterns, genetic diversity, and genetic differentiation between populations. Genetic differentiation was relatively strong between wild and cultivated C. canephora shrubs, and both gene pools harbored multiple unique alleles. Strong genetic differentiation was also observed between wild populations. The level of genetic diversity in wild populations was similar to that of the INERA Yangambi Coffee Collection, but local wild genotypes were mostly missing from that collection. Shrubs grown in the backyards were genetically similar to the breeding material from INERA Yangambi. Most C. canephora that is grown in local backyards originated from INERA breeding programs, while a few shrubs were obtained directly from surrounding forests. The INERA Yangambi Coffee Collection could benefit from an enrichment with local wild genotypes to increase the genetic resources available for breeding purposes and to support ex situ conservation.

The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species' population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate 'intactness scores': the remaining proportion of an 'intact' reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region's major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems.

The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.

Leaf traits are known to be strong predictors of plant performance and can be expected to (co)vary along environmental gradients. We investigated the variation, integration, environmental relationships and evolutionary history of leaf functional traits in the genus Coffea, typically a rainforest understorey shrub, across Africa. A better understanding of the adaptive processes involved in leaf trait evolution can inform the use and conservation of coffee genetic resources in a changing climate. We used phylogenetic comparative methods to investigate the evolution of six leaf traits measured from herbarium specimens of 58 African Coffea species. We added environmental data and data on maximum plant height for each species to test trait-environment correlations in various (sub)clades, and we compared continuous trait evolution models to identify variables driving trait diversification. Substantial leaf trait variation was detected across the genus Coffea in Africa, which was mostly interspecific. Of these traits, stomatal size and stomatal density exhibited a clear trade-off. We observed low densities of large stomata in early-branching lineages and higher densities of smaller stomata in more recent taxa, which we hypothesize to be related to declining CO2 levels since the mid-Miocene. Brownian motion evolution was rejected in favor of white noise or Ornstein-Uhlenbeck models for all traits, implying these traits are adaptively significant rather than driven by pure drift. The evolution of leaf area was likely driven by precipitation, with smaller leaves in drier climates across the genus. Generally, Coffea leaf traits appear to be evolutionarily labile and governed by stabilizing selection, though evolutionary patterns and correlations differ depending on the traits and clades considered. Our study highlights the importance of a phylogenetic perspective when studying trait relationships across related taxa, as well as the consideration of various taxonomic ranges.

Inherited retinal disorders (IRD) are a highly heterogeneous group of retinal diseases often characterized by progressive bilateral degeneration of rod and cone photoreceptors. Very little information is available on the genotype and phenotype of IRD in Central Africa. We investigated genetic causes of IRD in a well-characterized group of patients from the Democratic Republic of Congo (DRC). Ten patients, from eight families, with a clinical diagnosis of IRD in Kinshasa (DRC) were investigated. Each patient underwent general, dysmorphological and ophthalmic examination. DNA was extracted in the Centre for Human Genetics of the University of Kinshasa and clinical Whole Genome Sequencing (cWGS) was performed at Illumina Clinical Service Laboratory through the Illumina iHope program. The eight probands comprised 4 males and 4 females aged between 17.5 and 76 years. Nyctalopia and reduced visual acuity were the main complaints. All patients had normal hearing and were nondysmorphic. Fundus examination revealed bone-spicule pigment in all patients. Twelve plausible causal variants were identified in six genes: ADAM9, RP1, MERTK, CYP4V2, USH2A, and IFT140. One SNV and one intragenic CNV were novel. The SNV was assumed to be in trans with an intragenic SNV in three families, consistent with the well-known autosomal recessive inheritance for IRD in those genes. We report on the first cohort of African IRD patients investigated by cWGS. Our results indicate that also in Congolese patients, the spectrum of causal genes is broad and we expand the spectrum of causal variants in known IRD genes. This report demonstrates the power of cWGS, especially for genetically heterogeneous diseases.

Clade I monkeypox virus is endemic in DR Congo. We aim to describe the epidemiological trends of the cocirculating subclades Ia and Ib mpox outbreaks in Kinshasa, DR Congo. This retrospective observational study included suspected and laboratory-confirmed mpox cases reported between Jan 1, 2023, and Oct 31, 2024, in Kinshasa. Skin lesion swabs or blood samples were collected as part of a routine countrywide mpox surveillance programme. To confirm the diagnosis of mpox, all samples were tested at the Institut National de Recherche Biomédicale (INRB) using real-time PCR. Whole-genome sequencing was conducted for phylogenomic analysis and assessment of APOBEC3 type mutations. Samples that remained unassigned to subclade Ia or Ib after whole-genome sequencing and real-time PCR were labelled as an unknown subclade. As part of routine disease surveillance, 1479 suspected mpox cases were reported in Kinshasa. Samples were collected from 1314 suspected mpox cases and tested by PCR at the INRB. 440 (34%) of 1314 suspected cases had PCR confirmed mpox, with the first confirmed mpox case detected on Aug 18, 2023. 262 (60%) of 440 cases were male, 172 (39%) were female, and six (1%) were unknown, and the median age was 26 years (IQR 19-34). The epidemiological curve suggests two distinct periods during the 2023-24 outbreaks in Kinshasa. Between Aug 18, 2023, and June 30, 2024 (period 1), 218 suspected mpox cases underwent investigation and 24 (11%) were PCR confirmed as mpox; all cases were identified as subclade Ia. After a decline in suspected and confirmed cases in early 2024, the first confirmed subclade Ib mpox case in Kinshasa was reported on July 1, 2024. Between July 1 and Oct 31, 2024 (period 2), 1096 suspected mpox cases were reported and 416 (38%) were PCR confirmed as mpox. In-depth epidemiological case investigations during period 1 identified three small, self-limiting transmission chains between August and September, 2023. Case investigation data were available for 127 cases with PCR confirmed mpox, including clinical symptom data available for 61 (64%) of 95 with subclade Ia. The most commonly reported symptoms were fever (49 [80%] of 61) and skin rash (48 [79%]). The most common lesion locations were genital or anorectal (35 [64%] of 55 cases with available data). Case investigation data were available for 32 cases with subclade Ib mpox, including clinical symptom data available for 21 (66%) with subclade Ib. The most commonly reported symptoms were skin rash (18 [86%] of 21) and fever (12 [57%]). Genital or anorectal involvement was reported in 13 (68%) of 19 cases with available lesion location data. Genomic analysis shows five separate self-limiting clusters of subclade Ia (group II sampled from August, 2023, to August, 2024) and two larger clusters (occurring from July, 2024, to October, 2024, in period 2) belonging to subclade Ia (group II) and subclade Ib. 32 (68%) of 47 mutations for subclade Ia cluster outbreak and 28 (72%) of 39 mutations for subclade Ib outbreak were consistent with APOBEC3 driven changes. Sustained human-to-human transmission occurred after repeated self-limiting introductions of subclade Ia documented since 2023, which has cocirculated with subclade Ib in Kinshasa from July, 2024. Increased APOBEC3 driven changes in the new subclade Ia lineage support a shift towards human-to-human transmission. These findings reveal important changes in mpox transmission dynamics and suggests that any monkeypox virus subclade has the potential to cause sustained human outbreaks when favourable transmission conditions are met. Belgian Directorate-General for Development Cooperation and Humanitarian Aid; the Research Foundation Flanders; Institute of Tropical Medicine Structurele Onderzoeksfinanciering (Flemish Government; Science, Technology, and Innovation); Global Health European and Developing Countries Clinical Trials Partnership 3 Joint Undertaking; the US Department of Defense Threat Reduction Agency; the US Department for Agriculture Research Service; Canadian Institutes of Health Research; International Development Research Centre; US National Institute of Allergy and Infectious Diseases, National Institutes of Health; and Wellcome Trust.