The COVID-19 pandemic has ushered in high-throughput sequencing technology as an essential public health tool. Scaling up and operationalizing genomics in Africa is crucial as enhanced capacity for genome sequencing could address key health problems relevant to African populations. High-quality genomics research can be leveraged to improve diagnosis, understand the aetiology of unexplained illnesses, improve surveillance of infectious diseases and inform efficient control and therapeutic methods of known, rare and emerging infectious diseases. Achieving these within Africa requires strong commitment from stakeholders. A roadmap is needed to guide training of scientists, infrastructural development, research funding, international collaboration as well as promote public-private partnerships. Although the COVID-19 pandemic has significantly boosted genomics capacity in Africa, the continent still lags other regions. Here, we highlighted key initiatives in genomics research and efforts to address health challenges facing the diverse and fast-growing populations on the continent. We explore the scalability of genomic tools and techniques to tackle a broader range of infectious diseases in Africa, a continent that desperately requires a boost from genomic science.

Molecular biology has revealed that complex life phenomena can be treated as the result of many gene interactions. Investigating these interactions and understanding the intrinsic mechanisms of biological systems using gene expression data have attracted a lot of attention. As a typical gene regulatory network (GRN) inference method, the S-system has been utilized to deal with small-scale network identification. However, it is extremely difficult to optimize it to infer medium-to-large networks. This paper proposes a novel parallel swarm intelligent algorithm, PGRNIG, to optimize the parameters of the S-system. We employed the clone selection strategy to improve the whale optimization algorithm (CWOA). To enhance the time efficiency of CWOA optimization, we utilized a parallel CWOA (PCWOA) based on the compute unified device architecture (CUDA) platform. Decomposition strategy and L1 regularization were utilized to reduce the search space and complexity of GRN inference. We applied the PGRNIG algorithm on three synthetic datasets and two real time-series expression datasets of the species of Escherichia coli and Saccharomyces cerevisiae. Experimental results show that PGRNIG could infer the gene regulatory network more accurately than other state-of-the-art methods with a convincing computational speed-up. Our findings show that CWOA and PCWOA have faster convergence performances than WOA.

The traditional way for discovering genes which drive cancer (namely cancer drivers) neglects the dynamic information of cancer development, even though it is well known that cancer progresses dynamically. To enhance cancer driver discovery, we expand cancer driver concept to dynamic cancer driver as a gene driving one or more bio-pathological transitions during cancer progression. Our method refers to the fact that cancer should not be considered as a single process but a compendium of altered biological processes causing the disease to develop over time. Reciprocally, different drivers of cancer can potentially be discovered by analysing different bio-pathological pathways. We propose a novel approach for causal inference of genes driving one or more core processes during cancer development (i.e. dynamic cancer driver). We use the concept of pseudotime for inferring the latent progression of samples along a biological transition during cancer and identifying a critical event when such a process is significantly deviated from normal to carcinogenic. We infer driver genes by assessing the causal effect they have on the process after such a critical event. We have applied our method to single-cell and bulk sequencing datasets of breast cancer. The evaluation results show that our method outperforms well-recognized cancer driver inference methods. These results suggest that including information of the underlying dynamics of cancer improves the inference process (in comparison with using static data), and allows us to discover different sets of driver genes from different processes in cancer. R scripts and datasets can be found at https://github.com/AndresMCB/DynamicCancerDriver.

The elevated levels of inflammatory cytokines have attracted much attention during the treatment of COVID-19 patients. The conclusions of current observational studies are often controversial in terms of the causal effects of COVID-19 on various cytokines because of the confounding factors involving underlying diseases. To resolve this problem, we conducted a Mendelian randomization analysis by integrating the GWAS data of COVID-19 and 41 cytokines. As a result, the levels of 2 cytokines were identified to be promoted by COVID-19 and had unsignificant pleiotropy. In comparison, the levels of 10 cytokines were found to be inhibited and had unsignificant pleiotropy. Among down-regulated cytokines, CCL2, CCL3 and CCL7 were members of CC chemokine family. We then explored the potential molecular mechanism for a significant causal association at a single cell resolution based on single-cell RNA data, and discovered the suppression of CCL3 and the inhibition of CCL3-CCR1 interaction in classical monocytes (CMs) of COVID-19 patients. Our findings may indicate that the capability of COVID-19 in decreasing the chemotaxis of lymphocytes by inhibiting the CCL3-CCR1 interaction in CMs.

Tongue squamous cell carcinoma (TSCC) is considered the most common malignant tumor among the oral squamous cell carcinomas with a poor prognosis. Understanding the underlying molecular mechanisms that underpin TSCC and its treatments is the focus of the research. Deregulated expression of microRNAs (miRNAs) has recently been implicated in various biological processes linked to cancer. Therefore, in this study, we attempted to investigate miRNAs and their targets expressed in TSCC, which could be involved in its oncogenesis. We performed next-generation sequencing of small RNAs and transcriptomes in H357 TSCC cell line and human oral keratinocytes as a control to find miRNAs and mRNAs that are differentially expressed (DE), which were then supplemented with additional expression datasets from databases, yielding 269 DE miRNAs and 2094 DE genes. The target prediction followed by pathway and disease function analysis revealed that the DE targets were significantly associated with the key processes and pathways, such as apoptosis, epithelial-mesenchymal transition, endocytosis and vascular endothelial growth factor signaling pathways. Furthermore, the top 12 DE targets were chosen based on their involvement in more than one cancer-related pathway, of which 6 genes are targeted by miR-128-3p. Real-time quantitative PCR validation of this miRNA and its targets in H357 and SCC9 TSCC cells confirmed their possible targeting from their reciprocal expression, with MAP2K7 being a critical target that might be involved in oncogenesis and progression of TSCC by acting as a tumor suppressor. Further research is underway to understand how miR-128-3p regulates oncogenesis in TSCC via MAP2K7 and associated pathways.