Repurposing an integrated national influenza platform for genomic surveillance of SARS-CoV-2 in Ghana: a molecular epidemiological analysis.

BACKGROUND: Genomic surveillance of SARS-CoV-2 is crucial for monitoring the spread of COVID-19 and guiding public health decisions, but the capacity for SARS-CoV-2 testing and sequencing in Africa is low. We integrated SARS-CoV-2 surveillance into an existing influenza surveillance network with the aim of providing insights into SARS-CoV-2 transmission and genomics in Ghana. METHODS: In this molecular epidemiological analysis, which is part of a wider multifaceted prospective observational study, we collected national SARS-CoV-2 test data from 35 sites across 16 regions in Ghana from Sept 1, 2020, to Nov 30, 2021, via the Ghanaian integrated influenza and SARS-CoV-2 surveillance network. SARS-CoV-2-positive samples collected through this integrated national influenza surveillance network and from international travellers arriving in Accra were sequenced with Oxford Nanopore Technology sequencing and the ARTIC tiled amplicon method. The sequence lineages were typed with pangolin and the phylogenetic analysis was conducted with IQ-Tree2 and TreeTime. FINDINGS: During the study period, 5495 samples were submitted for diagnostic testing through the national influenza surveillance network (2121 [46·1%] of 4021 samples with complete demographic data were from female individuals and 2479 [53·9%] of 4021 samples were from male individuals). We also obtained 2289 samples from travellers who arrived in Accra and had a positive lateral flow test, of whom 1626 (71·0%, 95% CI 69·1-72·9) were confirmed to be SARS-CoV-2 positive. Co-circulation of influenza and SARS-CoV-2 in Ghana was detected, with increased cases of influenza in November, 2020, November, 2021, and January and June, 2021. In 4124 samples from individuals with influenza-like illness, SARS-CoV-2 was identified in 583 (14·1%, 95% CI 13·1-15·2) samples and influenza in 356 (8·6%, 7·8-9·5). Conversely, in 476 samples from individuals with of severe acute respiratory illness, SARS-CoV-2 was detected in 58 (12·2%, 9·5-15·5) samples and influenza in 95 (19·9%, 16·5-23·9). We detected four waves of SARS-CoV-2 infections in Ghana; each wave was driven by a different variant: B.1 and B.1.1 were the most prevalent lineages in wave 1, alpha (B.1.1.7) was responsible for wave 2, delta (B.1.617.2) and its sublineages (closely related to delta genomes from India) were responsible for wave 3, and omicron variants were responsible for wave 4. We detected omicron variants among 47 (32%) of 145 samples from travellers during the start of the omicron spread in Ghana (wave 4). INTERPRETATION: This study shows the value of repurposing existing influenza surveillance platforms to monitor SARS-CoV-2. Influenza continued to circulate in Ghana in 2020 and 2021, and remained a major cause of severe acute respiratory illness. We detected importations of SARS-CoV-2 variants into Ghana, including those that did or did not lead to onward community transmission. Investment in strengthening national influenza surveillance platforms in low-income and middle-income countries has potential for ongoing monitoring of SARS-CoV-2 and future pandemics. FUNDING: The EDCTP2 programme supported by the EU.

Revealing nuclear receptor hub modules from Basal-like breast cancer expression networks.

Nuclear receptors are a class of transcriptional factors. Together with their co-regulators, they regulate development, homeostasis, and metabolism in a ligand-dependent manner. Their ability to respond to environmental stimuli rapidly makes them versatile cellular components. Their coordinated activities regulate essential pathways in normal physiology and in disease. Due to their complexity, the challenge remains in understanding their direct associations in cancer development. Basal-like breast cancer is an aggressive form of breast cancer that often lacks ER, PR and Her2. The absence of these receptors limits the treatment for patients to the non-selective cytotoxic and cytostatic drugs. To identify potential drug targets it is essential to identify the most important nuclear receptor association network motifs in Basal-like subtype progression. This research aimed to reveal the transcriptional network patterns, in the hope to capture the underlying molecular state driving Basal-like oncogenesis. In this work, we illustrate a multidisciplinary approach of integrating an unsupervised machine learning clustering method with network modelling to reveal unique transcriptional patterns (network motifs) underlying Basal-like breast cancer. The unsupervised clustering method provides a natural stratification of breast cancer patients, revealing the underlying heterogeneity in Basal-like. Identification of gene correlation networks (GCNs) from Basal-like patients in both the TCGA and METABRIC databases revealed three critical transcriptional regulatory constellations that are enriched in Basal-like. These represent critical NR components implicated in Basal-like breast cancer transcription. This approach is easily adaptable and applicable to reveal critical signalling relationships in other diseases.