While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genomewide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/ South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.Latin America | population genetics | Salvador SCAALA | Bambuí Cohort Study of Ageing | Pelotas Birth Cohort Study L atin Americans, who are classical models of the effects of admixture in human populations (1, 2), remain underrepresented in studies of human genomic diversity, notwithstanding recent studies (3, 4). Indeed, no large genome-wide study on admixed South Americans has been conducted so far. Brazil is the largest and most populous Latin-American country. Its over 200 million inhabitants are the product of post-Columbian admixture between Amerindians, Europeans colonizers or immigrants, and African slaves (1). Interestingly, Brazil was the destiny of nearly 40% of the African diaspora, receiving seven times more slaves than the United States (nearly 4 million vs. 600,000).Here, we present results of the EPIGEN Brazil Initiative (https:// epigen.grude.ufmg.br), the most comprehensive up-to-date genomic analysis of a Latin-American population. We genotyped nearly 2.2 million SNPs in 6,487 admixed individuals from three population-based cohorts from different regions with distinct demographic and socioeconomic backgrounds and sequenced the whole genome of 30 individuals from these populations at an To whom correspondence should be addressed. Email: edutars@ic...

The Transatlantic Slave Trade transported more than 9 million Africans to the Americas between the early 16th and the mid-19th centuries. We performed a genome-wide analysis using 6,267 individuals from 25 populations to infer how different African groups contributed to North-, South-American, and Caribbean populations, in the context of geographic and geopolitical factors, and compared genetic data with demographic history records of the Transatlantic Slave Trade. We observed that West-Central Africa and Western Africa-associated ancestry clusters are more prevalent in northern latitudes of the Americas, whereas the South/East Africa-associated ancestry cluster is more prevalent in southern latitudes of the Americas. This pattern results from geographic and geopolitical factors leading to population differentiation. However, there is a substantial decrease in the between-population differentiation of the African gene pool within the Americas, when compared with the regions of origin from Africa, underscoring the importance of historical factors favoring admixture between individuals with different African origins in the New World. This between-population homogenization in the Americas is consistent with the excess of West-Central Africa ancestry (the most prevalent in the Americas) in the United States and Southeast-Brazil, with respect to historical-demography expectations. We also inferred that in most of the Americas, intercontinental admixture intensification occurred between 1750 and 1850, which correlates strongly with the peak of arrivals from Africa. This study contributes with a population genetics perspective to the ongoing social, cultural, and political debate regarding ancestry, admixture, and the mestizaje process in the Americas.

Western South America was one of the worldwide cradles of civilization. The well-known Inca Empire was the tip of the iceberg of an evolutionary process that started 11,000 to 14,000 years ago. Genetic data from 18 Peruvian populations reveal the following: 1) The between-population homogenization of the central southern Andes and its differentiation with respect to Amazonian populations of similar latitudes do not extend northward. Instead, longitudinal gene flow between the northern coast of Peru, Andes, and Amazonia accompanied cultural and socioeconomic interactions revealed by archeology. This pattern recapitulates the environmental and cultural differentiation between the fertile north, where altitudes are lower, and the arid south, where the Andes are higher, acting as a genetic barrier between the sharply different environments of the Andes and Amazonia. 2) The genetic homogenization between the populations of the arid Andes is not only due to migrations during the Inca Empire or the subsequent colonial period. It started at least during the earlier expansion of the Wari Empire (600 to 1,000 years before present). 3) This demographic history allowed for cases of positive natural selection in the high and arid Andes vs. the low Amazon tropical forest: in the Andes, a putative enhancer inHAND2-AS1(heart and neural crest derivatives expressed 2 antisense RNA1, a noncoding gene related to cardiovascular function) and rs269868-C/Ser1067 inDUOX2(dual oxidase 2, related to thyroid function and innate immunity) genes and, in the Amazon, the gene encoding for the CD45 protein, essential for antigen recognition by T and B lymphocytes in viral–host interaction.

Mitochondria are organelles that perform major roles in cellular operation. Thus, alterations in mitochondrial genome (mtGenome) may lead to mitochondrial dysfunction and cellular deregulation, influencing carcinogenesis. Gastric cancer (GC) is one of the most incident and mortal types of cancer in Brazil, particularly in the Amazon region. Here, we sequenced and compared the whole mtGenome extracted from FFPE tissue samples of GC patients (tumor and internal control – IC) and cancer-free individuals (external control – EC) from this region. We found 3-fold more variants and up to 9-fold more heteroplasmic regions in tumor when compared to paired IC samples. Moreover, tumor presented more heteroplasmic variants when compared to EC, while IC and EC showed no significant difference when compared to each other. Tumor also presented substantially more variants in the following regions: MT-RNR1, MT-ND5, MT-ND4, MT-ND2, MT-DLOOP1 and MT-CO1. In addition, our haplogroup results indicate an association of Native American ancestry (particularly haplogroup C) to gastric cancer development. To the best of our knowledge, this is the first study to sequence the whole mtGenome from FFPE samples and to apply mtGenome analysis in association to GC in Brazil.

box What is already known about this subject? ► Computer-assisted systems for health image analysis have improved the medical decision-making process for diagnosing and analysing the progression of various diseases. ► Diseases affecting gastric tissue are a worldwide health problem. ► Deep learning applications presented good results in different domains, however its application on gastric tissue analysis is recent, poorly analysed, and standardised. What are the new findings? ► We provide a literature categorisation, based on the method and related tasks, identifying the most widely adopted deep learning architecture and data source used. ► This is the first systematic review dedicated to map gastric tissue deep learning applications covering a broad spectrum, also listing and evaluating open source tools. ► We identified gaps evaluation metrics, image collection availability and, consequently, implications for experimental reproducibility.How might it impact on clinical practice in the foreseeable future?► Deep learning applications can provide greater and more efficient workflow support and extraction of important information from histological images, consequently, replicable studies need to be conducted clearly, and transparently, also providing the data used.AbSTrACT background In recent years, deep learning has gained remarkable attention in medical image analysis due to its capacity to provide results comparable to specialists and, in some cases, surpass them. Despite the emergence of deep learning research on gastric tissues diseases, few intensive reviews are addressing this topic.Method We performed a systematic review related to applications of deep learning in gastric tissue disease analysis by digital histology, endoscopy and radiology images.Conclusions This review highlighted the high potential and shortcomings in deep learning research studies applied to gastric cancer, ulcer, gastritis and non-malignant diseases. Our results demonstrate the effectiveness of gastric tissue analysis by deep learning applications. Moreover, we also identified gaps of evaluation metrics, and image collection availability, therefore, impacting experimental reproducibility.

EPIGEN-Brazil is one of the largest Latin American initiatives at the interface of human genomics, public health, and computational biology. Here, we present two resources to address two challenges to the global dissemination of precision medicine and the development of the bioinformatics know-how to support it. To address the underrepresentation of non-European individuals in human genome diversity studies, we present the EPIGEN-5M+1KGP imputation panel-the fusion of the public 1000 Genomes Project (1KGP) Phase 3 imputation panel with haplotypes derived from the EPIGEN-5M data set (a product of the genotyping of 4.3 million SNPs in 265 admixed individuals from the EPIGEN-Brazil Initiative). When we imputed a target SNPs data set (6487 admixed individuals genotyped for 2.2 million SNPs from the EPIGEN-Brazil project) with the EPIGEN-5M+1KGP panel, we gained 140,452 more SNPs in total than when using the 1KGP Phase 3 panel alone and 788,873 additional high confidence SNPs ( ≥ 0.8). Thus, the major effect of the inclusion of the EPIGEN-5M data set in this new imputation panel is not only to gain more SNPs but also to improve the quality of imputation. To address the lack of transparency and reproducibility of bioinformatics protocols, we present a conceptual Scientific Workflow in the form of a website that models the scientific process (by including publications, flowcharts, masterscripts, documents, and bioinformatics protocols), making it accessible and interactive. Its applicability is shown in the context of the development of our EPIGEN-5M+1KGP imputation panel. The Scientific Workflow also serves as a repository of bioinformatics resources.

53 4169-007, Portugal. 54 21 CIBIO/InBIO: Research Center in Biodiversity and Genetic Resources, Vairão, 4485-55 661, Portugal. 56 Abstract 76 The Transatlantic Slave Trade transported more than 9 million Africans to the Americas 77 between the early 16th and the mid-19th centuries. We performed genome-wide 78 analysis of 6,267 individuals from 22 populations and observed an enrichment in West-79 African ancestry in northern latitudes of the Americas, whereas South/East African 80 ancestry is more prevalent in southern South-America. This pattern results from distinct 81 geographic and geopolitical factors leading to population differentiation. However, we 82 observed a decrease of 68% in the African gene pool between-population diversity 83 within the Americas when compared to the regions of origin from Africa, underscoring 84 the importance of historical factors favoring admixture between individuals with 85 different African origins in the New World. This is consistent with the excess of West-86 Central Africa ancestry (the most prevalent in the Americas) in the US and Southeast-87 Brazil, respect to historical-demography expectations. Also, in most of the Americas, 88 admixture intensification occurred between 1,750 and 1,850, which correlates strongly 89 with the peak of arrivals from Africa. This study contributes with a population genetics 90 perspective to the ongoing social, cultural and political debate regarding ancestry, race, 91 and admixture in the Americas.92 93 Significance Statement 94 Differently from most genetic studies, that have estimated the overall African ancestry 95 in the Americas, we perform a finer geographic analysis and infer how different African 96 groups contributed to North-, South-American and Caribbean populations, in the 97 context of geographic and geopolitical factors. We also perform a formal comparison of 98 information from demographic history records of the Transatlantic Slave Trade with 99 inferences based on genomic diversity of current populations. Our approach reveals the 100 6 distinct regional African ancestry roots of different populations from North-, South-101 America and the Caribe and other important aspects of the historical process of 102 mestizaje and its dynamics in the American continent. 103 104 157(from Ghana, mean: 18%) ( Fig. 2A and B, SI Appendix, Table S3). 158The Western Africa-associated ancestry cluster has its highest proportions in Puerto 159 Ricans (38% of African ancestry), Colombians (27%) and US African-Americans (19-160 20%, purple in Fig. 1, SI Appendix, Table S1), while Brazilians have the lowest 161 proportion (<9%), limited to a Mandinka-like (Gambia) contribution and with no 162

Mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) are complex diseases with their molecular architecture not elucidated. APOE, Amyloid Beta Precursor Protein (APP), and Presenilin-1 (PSEN1) are well-known genes associated with both MCI and AD. Recently, epigenetic alterations and dysregulated regulatory elements, such as microRNAs (miRNAs), have been reported associated with neurodegeneration. In this study, differential expression analysis (DEA) was performed for genes and miRNAs based on microarray and RNA-Seq data. Global gene profile of healthy individuals, early and late mild cognitive impairment (EMCI and LMCI, respectively), and AD was obtained from ADNI Cohort. miRNA global profile of healthy individuals and AD patients was extracted from public RNA-Seq data. DEA performed with limma package on ADNI Cohort data highlighted eight differential expressed (DE) genes (AGER, LINC00483, MMP19, CATSPER1, ARFGAP1, GPER1, PHLPP2, TRPM2) (false discovery rate (FDR) p-value < 0.05) between EMCI and LMCI patients. Previous molecular studies showed associations between these genes with dementia and neurological-related pathways. Five dysregulated miRNAs were identified by DEA performed with RNA-Seq data and edgeR (FDR p-value < 0.002). All reported miRNAs in AD interact with the aforementioned genes. Our integrative transcriptomic analysis was able to identify a set of miRNA–gene interactions that may be involved in cognitive and neurodegeneration processes.