Distribution and asymptotic behavior of the phylogenetic transfer distance.

The transfer distance (TD) was introduced in the classification framework and studied in the context of phylogenetic tree matching. Recently, Lemoine et al. (Nature 556(7702):452-456, 2018. https://doi.org/10.1038/s41586-018-0043-0 ) showed that TD can be a powerful tool to assess the branch support on large phylogenies, thus providing a relevant alternative to Felsenstein's bootstrap. This distance allows a reference branch[Formula: see text] in a reference tree [Formula: see text] to be compared to a branch b from another tree T (typically a bootstrap tree), both on the same set of n taxa. The TD between these branches is the number of taxa that must be transferred from one side of b to the other in order to obtain [Formula: see text]. By taking the minimum TD from [Formula: see text] to all branches in T we define the transfer index, denoted by [Formula: see text], measuring the degree of agreement of T with [Formula: see text]. Let us consider a reference branch [Formula: see text] having p tips on its light side and define the transfer support (TS) as [Formula: see text]. Lemoine et al. (2018) used computer simulations to show that the TS defined in this manner is close to 0 for random "bootstrap" trees. In this paper, we demonstrate that result mathematically: when T is randomly drawn, TS converges in probability to 0 when n tends to [Formula: see text]. Moreover, we fully characterize the distribution of [Formula: see text] on caterpillar trees, indicating that the convergence is fast, and that even when n is small, moderate levels of branch support cannot appear by chance.

The Transcription Factor 7-Like 2-Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Axis Connects Mitochondrial Biogenesis and Metabolic Shift with Stem Cell Commitment to Hepatic Differentiation.

Increasing evidence supports that modifications in the mitochondrial content, oxidative phosphorylation (OXPHOS) activity, and cell metabolism influence the fate of stem cells. However, the regulators involved in the crosstalk between mitochondria and stem cell fate remains poorly characterized. Here, we identified a transcriptional regulatory axis, composed of transcription factor 7-like 2 (TCF7L2) (a downstream effector of the Wnt/ß-catenin pathway, repressed during differentiation) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) (the master regulator of mitochondrial biogenesis, induced during differentiation), coupling the loss of pluripotency and early commitment to differentiation, to the initiation of mitochondrial biogenesis and metabolic shift toward OXPHOS. PGC-1α induction during differentiation is required for both mitochondrial biogenesis and commitment to the hepatocytic lineage, and TCF7L2 repression is sufficient to increase PGC-1α expression, mitochondrial biogenesis and OXPHOS activity. We further demonstrate that OXPHOS activity is required for the differentiation toward the hepatocytic lineage, thus providing evidence that bi-directional interactions control stem cell differentiation and mitochondrial abundance and activity. Stem Cells 2017;35:2184-2197.

Designing a course model for distance-based online bioinformatics training in Africa: The H3ABioNet experience.

Africa is not unique in its need for basic bioinformatics training for individuals from a diverse range of academic backgrounds. However, particular logistical challenges in Africa, most notably access to bioinformatics expertise and internet stability, must be addressed in order to meet this need on the continent. H3ABioNet (www.h3abionet.org), the Pan African Bioinformatics Network for H3Africa, has therefore developed an innovative, free-of-charge "Introduction to Bioinformatics" course, taking these challenges into account as part of its educational efforts to provide on-site training and develop local expertise inside its network. A multiple-delivery-mode learning model was selected for this 3-month course in order to increase access to (mostly) African, expert bioinformatics trainers. The content of the course was developed to include a range of fundamental bioinformatics topics at the introductory level. For the first iteration of the course (2016), classrooms with a total of 364 enrolled participants were hosted at 20 institutions across 10 African countries. To ensure that classroom success did not depend on stable internet, trainers pre-recorded their lectures, and classrooms downloaded and watched these locally during biweekly contact sessions. The trainers were available via video conferencing to take questions during contact sessions, as well as via online "question and discussion" forums outside of contact session time. This learning model, developed for a resource-limited setting, could easily be adapted to other settings.

Molecular and serological diagnosis of multiple bacterial zoonoses in febrile outpatients in Garissa County, north-eastern Kenya.

Bacterial zoonoses are diseases caused by bacterial pathogens that can be naturally transmitted between humans and vertebrate animals. They are important causes of non-malarial fevers in Kenya, yet their epidemiology remains unclear. We investigated brucellosis, Q-fever and leptospirosis in the venous blood of 216 malaria-negative febrile patients recruited in two health centres (98 from Ijara and 118 from Sangailu health centres) in Garissa County in north-eastern Kenya. We determined exposure to the three zoonoses using serological (Rose Bengal test for Brucella spp., ELISA for C. burnetti and microscopic agglutination test for Leptospira spp.) and real-time PCR testing and identified risk factors for exposure. We also used non-targeted metagenomic sequencing on nine selected patients to assess the presence of other possible bacterial causes of non-malarial fevers. Considerable PCR positivity was found for Brucella (19.4%, 95% confidence intervals [CI] 14.2-25.5) and Leptospira spp. (1.7%, 95% CI 0.4-4.9), and high endpoint titres were observed against leptospiral serovar Grippotyphosa from the serological testing. Patients aged 5-17 years old had 4.02 (95% CI 1.18-13.70, p-value = 0.03) and 2.42 (95% CI 1.09-5.34, p-value = 0.03) times higher odds of infection with Brucella spp. and Coxiella burnetii than those of ages 35-80. Additionally, patients who sourced water from dams/springs, and other sources (protected wells, boreholes, bottled water, and water pans) had 2.39 (95% CI 1.22-4.68, p-value = 0.01) and 2.24 (1.15-4.35, p-value = 0.02) times higher odds of exposure to C. burnetii than those who used unprotected wells. Streptococcus and Moraxella spp. were determined using metagenomic sequencing. Brucellosis, leptospirosis, Streptococcus and Moraxella infections are potentially important causes of non-malarial fevers in Garissa. This knowledge can guide routine diagnosis, thus helping lower the disease burden and ensure better health outcomes, especially in younger populations.

Complete Genome Sequencing and Comparative Phylogenomics of Nine African Swine Fever Virus (ASFV) Isolates of the Virulent East African p72 Genotype IX without Viral Sequence Enrichment.

African swine fever virus (ASFV) is endemic to African wild pigs (Phacochoerus and Potamochoerus), in which viral infection is asymptomatic, and Ornithodoros soft ticks. However, ASFV causes a lethal disease in Eurasian domestic pigs (Sus scrofa). While Sub-Saharan Africa is believed to be the original home of ASFV, publicly available whole-genome ASFV sequences show a strong bias towards p72 Genotypes I and II, which are responsible for domestic pig pandemics outside Africa. To reduce this bias, we hereby describe nine novel East African complete genomes in p72 Genotype IX and present the phylogenetic analysis of all 16 available Genotype IX genomes compared with other ASFV p72 clades. We also document genome-level differences between one specific novel Genotype IX genome sequence (KE/2013/Busia.3) and a wild boar cell-passaged derivative. The Genotype IX genomes clustered with the five available Genotype X genomes. By contrast, Genotype IX and X genomes were strongly phylogenetically differentiated from all other ASFV genomes. The p72 gene region, on which the p72-based virus detection primers are derived, contains consistent SNPs in Genotype IX, potentially resulting in reduced sensitivity of detection. In addition to the abovementioned cell-adapted variant, eight novel ASFV Genotype IX genomes were determined: five from viruses passaged once in primary porcine peripheral blood monocytes and three generated from DNA isolated directly from field-sampled kidney tissues. Based on this methodological simplification, genome sequencing of ASFV field isolates should become increasingly routine and result in a rapid expansion of knowledge pertaining to the diversity of African ASFV at the whole-genome level.

Establishing African genomics and bioinformatics programs through annual regional workshops.

The African BioGenome Project (AfricaBP) Open Institute for Genomics and Bioinformatics aims to overcome barriers to capacity building through its distributed African regional workshops and prioritizes the exchange of grassroots knowledge and innovation in biodiversity genomics and bioinformatics. In 2023, we implemented 28 workshops on biodiversity genomics and bioinformatics, covering 11 African countries across the 5 African geographical regions. These regional workshops trained 408 African scientists in hands-on molecular biology, genomics and bioinformatics techniques as well as the ethical, legal and social issues associated with acquiring genetic resources. Here, we discuss the implementation of transformative strategies, such as expanding the regional workshop model of AfricaBP to involve multiple countries, institutions and partners, including the proposed creation of an African digital database with sequence information relating to both biodiversity and agriculture. This will ultimately help create a critical mass of skilled genomics and bioinformatics scientists across Africa.

Chromosome-level genome assembly and population genomic resource to accelerate orphan crop lablab breeding.

Under-utilised orphan crops hold the key to diversified and climate-resilient food systems. Here, we report on orphan crop genomics using the case of Lablab purpureus (L.) Sweet (lablab) - a legume native to Africa and cultivated throughout the tropics for food and forage. Our Africa-led plant genome collaboration produces a high-quality chromosome-scale assembly of the lablab genome. Our assembly highlights the genome organisation of the trypsin inhibitor genes - an important anti-nutritional factor in lablab. We also re-sequence cultivated and wild lablab accessions from Africa confirming two domestication events. Finally, we examine the genetic and phenotypic diversity in a comprehensive lablab germplasm collection and identify genomic loci underlying variation of important agronomic traits in lablab. The genomic data generated here provide a valuable resource for lablab improvement. Our inclusive collaborative approach also presents an example that can be explored by other researchers sequencing indigenous crops, particularly from low and middle-income countries (LMIC).

Genomics of Adaptations in Ungulates.

Ungulates are a group of hoofed animals that have long interacted with humans as essential sources of food, labor, clothing, and transportation. These consist of domesticated, feral, and wild species raised in a wide range of habitats and biomes. Given the diverse and extreme environments inhabited by ungulates, unique adaptive traits are fundamental for fitness. The documentation of genes that underlie their genomic signatures of selection is crucial in this regard. The increasing availability of advanced sequencing technologies has seen the rapid growth of ungulate genomic resources, which offers an exceptional opportunity to understand their adaptive evolution. Here, we summarize the current knowledge on evolutionary genetic signatures underlying the adaptations of ungulates to different habitats.

Comparative Analysis of SLA-1, SLA-2, and DQB1 Genetic Diversity in Locally-Adapted Kenyan Pigs and Their Wild Relatives, Warthogs.

Swine leukocyte antigen (SLA) plays a central role in controlling the immune response by discriminating self and foreign antigens and initiating an immune response. Studies on SLA polymorphism have demonstrated associations between SLA allelic variants, immune response, and disease resistance. The SLA polymorphism is due to host-pathogen co-evolution resulting in improved adaptation to diverse environments making SLA a crucial genomic region for comparative diversity studies. Although locally-adapted African pigs have small body sizes, they possess increased resilience under harsh environmental conditions and robust immune systems with reported tolerance to some diseases, including African swine fever. However, data on the SLA diversity in these pigs are not available. We characterized the SLA of unrelated locally-adapted domestic pigs from Homa Bay, Kenya, alongside exotic pigs and warthogs. We undertook SLA comparative diversity of the functionally expressed SLA class I (SLA-1, SLA-2) and II (DQB1) repertoires in these three suids using the reverse transcription polymerase chain reaction (RT-PCR) sequence-based typing (SBT) method. Our data revealed higher genetic diversity in the locally-adapted pigs and warthogs compared to the exotic pigs. The nucleotide substitution rates were higher in the peptide-binding regions of the SLA-1, SLA-2, and DQB1 loci, indicative of adaptive evolution. We obtained high allele frequencies in the three SLA loci, including some breed-specific private alleles, which could guide breeders to increase their frequency through selection if confirmed to be associated with enhanced resilience. Our study contributes to the growing body of knowledge on genetic diversity in free-ranging animal populations in their natural environment, availing the first DQB1 gene data from locally-adapted Kenyan pigs.