ترغب بنشر مسار تعليمي؟ اضغط هنا

PCA and K-Means decipher genome

60   0   0.0 ( 0 )
 نشر من قبل Alexander Gorban
 تاريخ النشر 2005
  مجال البحث علم الأحياء
والبحث باللغة English




اسأل ChatGPT حول البحث

In this paper, we aim to give a tutorial for undergraduate students studying statistical methods and/or bioinformatics. The students will learn how data visualization can help in genomic sequence analysis. Students start with a fragment of genetic text of a bacterial genome and analyze its structure. By means of principal component analysis they ``discover that the information in the genome is encoded by non-overlapping triplets. Next, they learn how to find gene positions. This exercise on PCA and K-Means clustering enables active study of the basic bioinformatics notions. Appendix 1 contains program listings that go along with this exercise. Appendix 2 includes 2D PCA plots of triplet usage in moving frame for a series of bacterial genomes from GC-poor to GC-rich ones. Animated 3D PCA plots are attached as separate gif files. Topology (cluster structure) and geometry (mutual positions of clusters) of these plots depends clearly on GC-content.



قيم البحث

اقرأ أيضاً

The Roma people, living throughout Europe, are a diverse population linked by the Romani language and culture. Previous linguistic and genetic studies have suggested that the Roma migrated into Europe from South Asia about 1000-1500 years ago. Geneti c inferences about Roma history have mostly focused on the Y chromosome and mitochondrial DNA. To explore what additional information can be learned from genome-wide data, we analyzed data from six Roma groups that we genotyped at hundreds of thousands of single nucleotide polymorphisms (SNPs). We estimate that the Roma harbor about 80% West Eurasian ancestry-deriving from a combination of European and South Asian sources- and that the date of admixture of South Asian and European ancestry was about 850 years ago. We provide evidence for Eastern Europe being a major source of European ancestry, and North-west India being a major source of the South Asian ancestry in the Roma. By computing allele sharing as a measure of linkage disequilibrium, we estimate that the migration of Roma out of the Indian subcontinent was accompanied by a severe founder event, which we hypothesize was followed by a major demographic expansion once the population arrived in Europe.
The role of positive selection in human evolution remains controversial. On the one hand, scans for positive selection have identified hundreds of candidate loci and the genome-wide patterns of polymorphism show signatures consistent with frequent po sitive selection. On the other hand, recent studies have argued that many of the candidate loci are false positives and that most apparent genome-wide signatures of adaptation are in fact due to reduction of neutral diversity by linked recurrent deleterious mutations, known as background selection. Here we analyze human polymorphism data from the 1,000 Genomes project (Abecasis et al. 2012) and detect signatures of pervasive positive selection once we correct for the effects of background selection. We show that levels of neutral polymorphism are lower near amino acid substitutions, with the strongest reduction observed specifically near functionally consequential amino acid substitutions. Furthermore, amino acid substitutions are associated with signatures of recent adaptation that should not be generated by background selection, such as the presence of unusually long and frequent haplotypes and specific distortions in the site frequency spectrum. We use forward simulations to show that the observed signatures require a high rate of strongly adaptive substitutions in the vicinity of the amino acid changes. We further demonstrate that the observed signatures of positive selection correlate more strongly with the presence of regulatory sequences, as predicted by ENCODE (Gerstein et al. 2012), than the positions of amino acid substitutions. Our results establish that adaptation was frequent in human evolution and provide support for the hypothesis of King and Wilson (King and Wilson 1975) that adaptive divergence is primarily driven by regulatory changes.
Because biological processes can make different loci have different evolutionary histories, species tree estimation requires multiple loci from across the genome. While many processes can result in discord between gene trees and species trees, incomp lete lineage sorting (ILS), modeled by the multi-species coalescent, is considered to be a dominant cause for gene tree heterogeneity. Coalescent-based methods have been developed to estimate species trees, many of which operate by combining estimated gene trees, and so are called summary methods. Because summary methods are generally fast, they have become very popular techniques for estimating species trees from multiple loci. However, recent studies have established that summary methods can have reduced accuracy in the presence of gene tree estimation error, and also that many biological datasets have substantial gene tree estimation error, so that summary methods may not be highly accurate on biologically realistic conditions. Mirarab et al. (Science 2014) presented the statistical binning technique to improve gene tree estimation in multi-locus analyses, and showed that it improved the accuracy of MP-EST, one of the most popular coalescent-based summary methods. Statistical binning, which uses a simple statistical test for combinability and then uses the larger sets of genes to re-calculate gene trees, has good empirical performance, but using statistical binning within a phylogenomics pipeline does not have the desirable property of being statistically consistent. We show that weighting the recalculated gene trees by the bin sizes makes statistical binning statistically consistent under the multispecies coalescent, and maintains the good empirical performance. Thus, weighted statistical binning enables highly accurate genome-scale species tree estimation, and is also statistical consistent under the multi-species coalescent model.
The human-associated microbiome is closely tied to human health and is of substantial clinical interest. Metagenomics-based tools are emerging for clinical diagnostics, tracking the spread of diseases, and surveillance of potential pathogens. In some cases, these tools are overcoming limitations of traditional clinical approaches. Metagenomics has limitations barring the tools from clinical validation. Once these hurdles are overcome, clinical metagenomics will inform doctors of the best, targeted treatment for their patients and provide early detection of disease. Here we present an overview of metagenomics methods with a discussion of computational challenges and limitations.
77 - Olga Zolotareva 2020
Aggregating transcriptomics data across hospitals can increase sensitivity and robustness of differential expression analyses, yielding deeper clinical insights. As data exchange is often restricted by privacy legislation, meta-analyses are frequentl y employed to pool local results. However, if class labels are inhomogeneously distributed between cohorts, their accuracy may drop. Flimma (https://exbio.wzw.tum.de/flimma/) addresses this issue by implementing the state-of-the-art workflow limma voom in a privacy-preserving manner, i.e. patient data never leaves its source site. Flimma results are identical to those generated by limma voom on combined datasets even in imbalanced scenarios where meta-analysis approaches fail.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا