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UKBB_noPCsA GWAS for human height in the UK Biobank. Linear regression without any structure correction---with only genotype, age, sex and sequencing array as covariates (unrelated British ancestry individuals only). See the paper for the plink command and more details.UKBB_sib_gwasA GWAS for human height in the UK Biobank sibs. Family-based sib-pair analysis. See the paper for the plink command and more details.IRL-GBR allele frequency differencesLogistic regression using self-identified as "White British" or "White Irish" in the UK Biobank were compared with distinct phenotype labels. See paper for plink command line and more details.BvI.nocovar.Irish.glm.logistic.gzGBR-TSI allele frequency differencesIndividuals from the GBR and TSI populations from 1000G Phase 3 were assigned binary phenotype labels and a chi square test was performed for allele frequency differences. See paper for the plink command line and more details.gwas.hwe1e6.geno05.nocovar.chisq.British.assoc.gzUK Biobank Acknowledgement Several recent papers have reported strong signals of selection on European polygenic height scores. These analyses used height effect estimates from the GIANT consortium and replication studies. Here, we describe a new analysis based on the the UK Biobank (UKB), a large, independent dataset. We find that the signals of selection using UKB effect estimates are strongly attenuated or absent. We also provide evidence that previous analyses were confounded by population stratification. Therefore, the conclusion of strong polygenic adaptation now lacks support. Moreover, these discrepancies highlight (1) that methods for correcting for population stratification in GWAS may not always be sufficient for polygenic trait analyses, and (2) that claims of differences in polygenic scores between populations should be treated with caution until these issues are better understood.

Objectives: Traditionally, summarization of research themes and trends within a given discipline was accomplished by manual review of scientific works in the field. However, with the ushering in of the age of “big data”, new methods for discovery of such information become necessary as traditional techniques become increasingly difficult to apply due to the exponential growth of document repositories. Our objectives are to develop a pipeline for unsupervised theme extraction and summarization of thematic trends in document repositories, and to test it by applying it to a specific domain. Methods: To that end, we detail a pipeline, which utilizes machine learning and natural language processing for unsupervised theme extraction, and a novel method for summarization of thematic trends, and network mapping for visualization of thematic relations. We then apply this pipeline to a collection of anesthesiology abstracts. Results: We demonstrate how this pipeline enables discovery of major themes and temporal trends in anesthesiology research and facilitates document classification and corpus exploration. Discussion: The relation of prevalent topics and extracted trends to recent events in both anesthesiology, and healthcare in general, demonstrates the pipeline’s utility. Furthermore, the agreement between the unsupervised thematic grouping and human-assigned classification validates the pipeline’s accuracy and demonstrates another potential use. Conclusion: The described pipeline enables summarization and exploration of large document repositories, facilitates classification, aids in trend identification. A more robust and user-friendly interface will facilitate the expansion of this methodology to other domains. This will be the focus of future work for our group. Rusanov et alData from "Trends in anesthesiology research: A machine learning approach to theme discovery and summarization" by Rusanov, Alexander, Miotto, Riccardo, Weng, Chunhua

UK Biobank custom height association statistics on ~700k genotyped SNPsThe zip file contains six files: (1) ukb_cal_v2_height_allancestry_10pcs_assoc_linear.tsv (2) ukb_cal_v2_height_allancestry_nopcs_assoc_linear.tsv (3) ukb_cal_v2_height_britishancestry_10pcs_assoc_linear.tsv (4) ukb_cal_v2_height_britishancestry_nopcs_assoc_linear.tsv (5) ukb_cal_v2_height_sibs_perm_qfam.tsv (6) ukb_cal_v2_height_wbsibs_perm_qfam.tsv (1) - (4) are height GWAS estimates on all samples / white British samples using 10 PCs as covariates or no PCs as covariates. Sex was included as covariate in all analyses. (3) is equivalent to the UK Biobank height GWAS from the Neale lab. The remaining small differences can be explained by genotype differences in the UK Biobank imputed data and genotyped data. (5) and (6) are family based estimates from 20166 sibling pairs of any ancestry (5) and 17358 sibling pairs where both siblings are of white British ancestry (6) in the UK Biobank. Pairs of samples with IBS0 > 0.0018 and Kinship coefficient > 0.185 were identified as sibling pairs. For the analyses in Sohail, Maier et al., only the subset of ~300,000 SNPs with SDS scores was used. For a description of the columns in files (1)-(4) please see the PLINK documentation for the ‘--linear’ command. Column “A2” has been added and denotes the non-effect allele. For a description of the columns in files (5) and (6) please see the PLINK documentation for the ‘--qfam’ command. Column “A2” has been added and denotes the non-effect allele. “EMP1” and “NP” refer to permutation p-value and number of permutations, respectively. Please note: These data are derived from the UK Biobank Resource under Application Number 18597.sohail_maier_2018.zip Genetic predictions of height differ among human populations and these differences have been interpreted as evidence of polygenic adaptation. These differences were first detected using SNPs genome-wide significantly associated with height, and shown to grow stronger when large numbers of sub-significant SNPs were included, leading to excitement about the prospect of analyzing large fractions of the genome to detect polygenic adaptation for multiple traits. Previous studies of height have been based on SNP effect size measurements in the GIANT Consortium meta-analysis. Here we repeat the analyses in the UK Biobank, a much more homogeneously designed study. We show that polygenic adaptation signals based on large numbers of SNPs below genome-wide significance are extremely sensitive to biases due to uncorrected population structure. More generally, our results imply that typical constructions of polygenic scores are sensitive to population structure and that population-level differences should be interpreted with caution.

The exact timing, route, and process of the initial peopling of the Americas remains uncertain despite much research. Archaeological evidence indicates the presence of humans as far as southern Chile by 14.6 thousand years ago (ka), shortly after the Pleistocene ice sheets blocking access from eastern Beringia began to retreat. Genetic estimates of the timing and route of entry have been constrained by the lack of suitable calibration points and low genetic diversity of Native Americans. We sequenced 92 whole mitochondrial genomes from pre-Columbian South American skeletons dating from 8.6 to 0.5 ka, allowing a detailed, temporally calibrated reconstruction of the peopling of the Americas in a Bayesian coalescent analysis. The data suggest that a small population entered the Americas via a coastal route around 16.0 ka, following previous isolation in eastern Beringia for ~2.4 to 9 thousand years after separation from eastern Siberian populations. Following a rapid movement throughout the Americas, limited gene flow in South America resulted in a marked phylogeographic structure of populations, which persisted through time. All of the ancient mitochondrial lineages detected in this study were absent from modern data sets, suggesting a high extinction rate. To investigate this further, we applied a novel principal components multiple logistic regression test to Bayesian serial coalescent simulations. The analysis supported a scenario in which European colonization caused a substantial loss of pre-Columbian lineages. xml files for BEAST1.8.0A total of 370 whole mitochondrial genomes (WMGs) corresponding to Native Central and South American populations were collected from published studies. Of note, the large dataset of 215 Mexican WMGs from Kumar et al. 2011 was not used to prevent an over-representation of Mexican samples. We randomly selected three replicate datasets of 87 sequences, all of which contained exclusively the five Native American haplogroups A2, B2, C1, D1, and D4h3a (table S3). We added 20 East Siberian individuals from sister lineages within haplogroups A, B, C and D in order to estimate the time of the split between Siberian and American lineages. We also added the 92 ancient WMGs from the study, as well as the Anzick-1 mitogenome, to obtain three replicate datasets of 200 sequences. The Anzick-1 WMG was included as it added a deep time calibration at 12.6 kya, was the only ancient D4h3a sequence available, and because the Anzick-1 individual can reasonably be considered a descendant of the first wave of colonizers.xml_files_for_BEAST1.8.0.zip

We have generated and made publicly available two very large networks of molecular interactions: 49,493 mouse-specific and 52,518 human-specific interactions. These networks were generated through automated analysis of 368,331 full-text research articles and 8,039,972 article abstracts from the PubMed database, using the GeneWays system. Our networks cover a wide spectrum of molecular interactions, such as bind, phosphorylate, glycosylate, and activate; 207 of these interaction types occur more than 1,000 times in our unfiltered, multi-species data set. Because mouse and human genes are linked through an orthological relationship, human and mouse networks are amenable to straightforward, joint computational analysis. Using our newly generated networks and known associations between mouse genes and cerebellar malformation phenotypes, we predicted a number of new associations between genes and five cerebellar phenotypes (small cerebellum, absent cerebellum, cerebellar degeneration, abnormal foliation, and abnormal vermis). Using a battery of statistical tests, we showed that genes that are associated with cerebellar phenotypes tend to form compact network clusters. Further, we observed that cerebellar malformation phenotypes tend to be associated with highly connected genes. This tendency was stronger for developmental phenotypes and weaker for cerebellar degeneration. Data from: Looking at Cerebellar Malformations through Text-Mined Interactomes of Mice and HumansSee original publication and documentation files included in this archive. Archive format is POSIX 'tar' archive compressed using GNU zip (gzip). The included data files are tab-separated ASCII. Some Matlab scripts are provided.iossifov-2009.tgz