Some statistical issues in population genetics

Ph.DDOCTOR OF PHILOSOPH

clrDV: a differential variability test for RNA-Seq data based on the skew-normal distribution

Background Pathological conditions may result in certain genes having expression variance that differs markedly from that of the control. Finding such genes from gene expression data can provide invaluable candidates for therapeutic intervention. Under the dominant paradigm for modeling RNA-Seq gene counts using the negative binomial model, tests of differential variability are challenging to develop, owing to dependence of the variance on the mean. Methods Here, we describe clrDV, a statistical method for detecting genes that show differential variability between two populations. We present the skew-normal distribution for modeling gene-wise null distribution of centered log-ratio transformation of compositional RNA-seq data. Results Simulation results show that clrDV has false discovery rate and probability of Type II error that are on par with or superior to existing methodologies. In addition, its run time is faster than its closest competitors, and remains relatively constant for increasing sample size per group. Analysis of a large neurodegenerative disease RNA-Seq dataset using clrDV successfully recovers multiple gene candidates that have been reported to be associated with Alzheimer’s disease

Linking the effects of helminth infection, diet and the gut microbiota with human whole-blood signatures

Helminth infection and dietary intake can affect the intestinal microbiota, as well as the immune system. Here we analyzed the relationship between fecal microbiota and blood profiles of indigenous Malaysians, referred to locally as Orang Asli, in comparison to urban participants from the capital city of Malaysia, Kuala Lumpur. We found that helminth infections had a larger effect on gut microbial composition than did dietary intake or blood profiles. Trichuris trichiura infection intensity also had the strongest association with blood transcriptional profiles. By characterizing paired longitudinal samples collected before and after deworming treatment, we determined that changes in serum zinc and iron levels among the Orang Asli were driven by changes in helminth infection status, independent of dietary metal intake. Serum zinc and iron levels were associated with changes in the abundance of several microbial taxa. Hence, there is considerable interplay between helminths, micronutrients and the microbiota on the regulation of immune responses in humans

Three dispersal routes out of Africa: A puzzling biogeographical history in freshwater planarians

Aim Freshwater planarians may have a wide geographical range despite their assumed low vagility. Found across four continents, Dugesia may have either an ancient origin on a large palaeo landmass, followed by colonisation in different regions before continental fragmentation, or a more recent origin and subsequent transoceanic dispersal. We seek to resolve between these two hypotheses. Location Africa, Eurasia and Australasia. Taxon Genus Dugesia (Platyhelminthes: Tricladida: Dugesiidae). Methods We used data from the sequencing of six gene fragments and comprehensive taxonomic sampling of Dugesia from across its distribution range to reconstruct the phylogeny of this genus using maximum likelihood and bayesian inference methods. We conducted two phylogenetic dating analyses using Platyhelminthes fossils and palaeogeological events. Basing on the time-calibrated molecular phylogenetic framework we evaluated the contribution of vicariance and dispersal to the biogeographical evolution of Dugesia. By reconstructing the ancestral areas and present-day potential distribution using BioGeoBEARS and niche modelling, we elucidated the biogeographical history of the genus. Results The present-day distribution of Dugesia is a result of different vicariance and dispersal events. However, we also found evidence of transoceanic dispersal. Consistent with previous hypotheses, Dugesia dates to the Upper Jurassic in the Afro-Malagasy Gondwana region. We unveiled a novel biogeographical scenario for the genus, involving multiple events of colonisation in Eurasia from continental Africa via at least three dispersal routes. Main conclusions Dugesia is an ancient genus having reached its present distribution through a complex history of dispersal and vicariant events following its origin in southern Gondwana. Despite the low vagility of Dugesia, we found evidence of their overseas dispersal

Heatmap - analysis of GSE60450 data set

Heatmap clustering with ward.D algorithm for the samples and genes

Supplementary R code

Supplementary R codes to produce the volcano plot and heat map described in T.F. Khang reviewer report for Chen, Lun & Smyth (2016)

COI ITS 28SrRNA Dugesia data.zip

Compilation of multiple sequence alignments of COI, ITS-1, 28SrRNA from <i>Dugesia</i> species

Updated monogeneaGM R scripts

updated monogeneaGM R scripts that are compatible with geomorph version 3.0.0

concatenation.R

R script for concatenating multiple sequence alignment