Somatic genetic aberrations in benign breast disease and the risk of subsequent breast cancer

It is largely unknown how the development of breast cancer (BC) is transduced by somatic genetic alterations in the benign breast. Since benign breast disease is an established risk factor for BC, we established a case-control study of women with a history of benign breast biopsy (BBB). Cases developed BC at least one year after BBB and controls did not develop BC over an average of 17 years following BBB. 135 cases were matched to 69 controls by age and type of benign change: non-proliferative or proliferation without atypia (PDWA). Whole-exome sequencing (WES) was performed for the BBB. Germline DNA (available from n = 26 participants) was utilized to develop a mutation-calling pipeline, to allow differentiation of somatic from germline variants. Among the 204 subjects, two known mutational signatures were identified, along with a currently uncatalogued signature that was significantly associated with triple negative BC (TNBC) (p = 0.007). The uncatalogued mutational signature was validated in 109 TNBCs from TCGA (p = 0.001). Compared to non-proliferative samples, PDWA harbors more abundant mutations at PIK3CA pH1047R (p < 0.001). Among the 26 BBB whose somatic copy number variation could be assessed, deletion of MLH3 is significantly associated with the mismatch repair mutational signature (p < 0.001). Matched BBB-cancer pairs were available for ten cases; several mutations were shared between BBB and cancers. This initial study of WES of BBB shows its potential for the identification of genetic alterations that portend breast oncogenesis. In future larger studies, robust personalized breast cancer risk indicators leading to novel interception paradigms can be assessed

Using an Unsupervised Clustering Model to Detect the Early Spread of SARS-CoV-2 Worldwide

Deciphering the population structure of SARS-CoV-2 is critical to inform public health management and reduce the risk of future dissemination. With the continuous accruing of SARS-CoV-2 genomes worldwide, discovering an effective way to group these genomes is critical for organizing the landscape of the population structure of the virus. Taking advantage of recently published state-of-the-art machine learning algorithms, we used an unsupervised deep learning clustering algorithm to group a total of 16,873 SARS-CoV-2 genomes. Using single nucleotide polymorphisms as input features, we identified six major subtypes of SARS-CoV-2. The proportions of the clusters across the continents revealed distinct geographical distributions. Comprehensive analysis indicated that both genetic factors and human migration factors shaped the specific geographical distribution of the population structure. This study provides a different approach using clustering methods to study the population structure of a never-seen-before and fast-growing species such as SARS-CoV-2. Moreover, clustering techniques can be used for further studies of local population structures of the proliferating virus

Additional file 1: of Discovering causal interactions using Bayesian network scoring and information gain

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