simons_genome_diversity_oct_2016.Rnw

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  61
  62 \title[Simons Genome Div.]{Simons Genome Diversity Project}
  63 \author[Don Armstrong]{Don L. Armstrong}
  64 \institute[IGB]{Institute for Genomic Biology, Computing Genomes
  65   for Reproductive Health, University of Illinois, Urbana-Champaign}
  66
  67 \begin{document}
  68
  69 <<load.libraries,echo=FALSE,results="hide",warning=FALSE,message=FALSE,error=FALSE,cache=FALSE>>=
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  73   cairo_pdf(tempfile(), width = width, height = height, ...)
  74 })
  75 options(digits=2)
  76 library("data.table")
  77 library("ggplot2")
  78 library("reshape2")
  79 library("grid")
  80 library("xtable")
  81
  82 @
  83
  84 \IfFileExists{figures/relevant_xkcd.png}{\frame[plain]{\centering \includegraphics[width=\textwidth,height=0.8\textheight,keepaspectratio]{figures/relevant_xkcd.png}
  85
  86     \url{https://xkcd.com/1706/}}}
  87
  88 \frame[plain]{\titlepage
  89   \begin{center}
  90     Code and slides are here:
  91
  92     \qrcode[padding]{http://dla2.us/p/genomdiv2016}
  93
  94     \url{http://dla2.us/p/genomdiv2016}
  95    \end{center}
  96 }
  97
  98
  99 \frame[plain]{
 100    \begin{center}
 101      \includegraphics[width=\textwidth,height=0.8\textheight,keepaspectratio]{genome_diversity_paper/title.png}
 102    \end{center}
 103 }
 104
 105 \begin{frame}{Sampling}
 106   \begin{itemize}
 107   \item 142 populations from Africa, America, Oceania, South Asia,
 108     East Asia, and West Eurasia (mostly indigenous)
 109   \item 300 samples sequenced at 34-83 fold coverage by Illumina
 110   \item Aligned using BWA-MEM
 111   \item Genotyped using special version of GATK and Fermikit
 112   \item Data available in EBI ($n=279$, PRJEB9586) and dbGAP ($n=21$, ?)
 113   \end{itemize}
 114 \end{frame}
 115
 116
 117 \begin{frame}[fragile]{Alignment Pipeline}
 118   \begin{itemize}
 119   \item Aligned to the “decoy” version of the human reference
 120     (hs37d5); supposedly improves alignment in misassembled regions or
 121     regions with CNVs?
 122   \item PCR-free data, though they marked optical duplicates marked
 123     using samblaster
 124   \end{itemize}
 125 \begin{minted}{bash}
 126 ./htscmd bamshuf -Oun128 in.bam tmp-pre \
 127 | ./htscmd bam2fq -as aln-se.fq.gz - \
 128 | ./trimadap \
 129 | ./bwa mem -pt8 hs37d5.fa - \
 130 | ./samblaster \
 131 | samtools view -uS - \
 132 | samtools sort -@4 -m512M - out-pre
 133 \end{minted}
 134 \end{frame}
 135
 136 \begin{frame}[fragile]{Genotyping}
 137   \begin{itemize}
 138   \item Reference-bias; novel variants, GATK assumes reference is more
 139     likely which may not be the case. Use prior of
 140     $(0.4995,0.001,0.4995)$ instead of default
 141     $(0.9985,0.001,0.0005)$.
 142     \begin{itemize}
 143     \item Unclear what the effect of this change is on the calling
 144     \item Maybe worth thinking about?
 145     \end{itemize}
 146   \item Also used Fermikit; apparently has comparable call rates to
 147     GATK and platypus
 148   \end{itemize}
 149 \begin{minted}{bash}
 150   java -Xmx2g -jar GenomeAnalysisTK.jar \
 151   -T UnifiedGenotyper -I srt.aln.bam \
 152   -L CHR_ID -R hs37d5.fa -dcov 600 -glm SNP \
 153   -out_mode EMIT_ALL_SITES -stand_call_conf 5.0 \
 154   -stand_emit_conf 5.0 -inputPrior 0.0010 \
 155   -inputPrior 0.4995 -D dbsnp_138.b37.vcf \
 156   -o CHR_ID.vcf -A GCContent -A BaseCounts
 157 \end{minted}
 158 \end{frame}
 159
 160 \begin{frame}{Fermikit vs Platypus vs GATK}
 161   \begin{columns}
 162     \column{0.5\textwidth}
 163     \includegraphics[width=\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/supplemental-014.png}
 164     \column{0.5\textwidth}
 165   FermiKit and Platypus call 3.17M more sites than GATK, but unclear
 166   whether those are real sites or not; they go into this in much more
 167   detail than I've digested yet.
 168 \end{columns}
 169 \end{frame}
 170
 171 \begin{frame}{Relatedness of Populations}
 172   \begin{columns}
 173     \column{0.7\textwidth}
 174     \includegraphics[width=0.5\textwidth,height=0.8\textheight,keepaspectratio]{genome_diversity_paper/fig1a_1.png}
 175     \includegraphics[width=0.5\textwidth,height=0.8\textheight,keepaspectratio]{genome_diversity_paper/fig1a_2.png}
 176     \column{0.3\textwidth}
 177     \begin{itemize}
 178     \item Neighbor joining tree based on pairwise divergence per nucleotide
 179     \item Deepest splits are in African populations
 180     \end{itemize}
 181   \end{columns}
 182 \end{frame}
 183
 184 \begin{frame}{PCA and Relatedness}
 185   \begin{center}
 186     \includegraphics[width=\textwidth,height=0.6\textheight,keepaspectratio]{genome_diversity_paper/fig_ed4.png}
 187   \end{center}
 188   \begin{itemize}
 189   \item Greatest variation seen in the African populations (orange)
 190   \item Other populations are much more similar to eachother in
 191     general
 192   \item Hapmap likely under-measured variation in Africa
 193   \end{itemize}
 194 \end{frame}
 195
 196 \begin{frame}
 197   \begin{center}
 198     \includegraphics[width=\textwidth,height=0.6\textheight,keepaspectratio]{genome_diversity_paper/fig1b.png}
 199   \end{center}
 200   \begin{itemize}
 201   \item Pygmy populations have lower X heterozygosity than other African populations
 202   \item Seen even after removing the third of X which is subject to selection
 203   \item Suggests that it's driven by demographic history, and the
 204     reduced diversity is due to male-driven admixture (also in non-Africans)
 205   \end{itemize}
 206 \end{frame}
 207
 208 \begin{frame}{Neanderthal Ancestry}
 209   \begin{center}
 210     \includegraphics[width=\textwidth,height=0.6\textheight,keepaspectratio]{genome_diversity_paper/fig1c.png}
 211   \end{center}
 212   \begin{itemize}
 213   \item No populations studied have a higher Neanderthal ancestry than
 214     East Asians
 215   \end{itemize}
 216 \end{frame}
 217
 218 \begin{frame}{Denisovan Ancestry}
 219   \begin{center}
 220     \includegraphics[width=\textwidth,height=0.6\textheight,keepaspectratio]{genome_diversity_paper/fig1d.png}
 221   \end{center}
 222   \begin{itemize}
 223   \item Oceanian groups have as much as 5\% Denisovan ancestry
 224   \item Eurasian differences in ancestry; some South Asians may have
 225     higher Denisovan than other Eurasians
 226   \end{itemize}
 227 \end{frame}
 228 g
 229
 230 \begin{frame}{Variation missed by hapmap}
 231   \begin{center}
 232     \includegraphics[width=\textwidth,height=0.8\textheight,keepaspectratio]{genome_diversity_paper/fig_ed1.png}
 233   \end{center}
 234   \begin{itemize}
 235   \item Hapmap is missing up to 8\% of the heterozygous sites in parts
 236     of Africa
 237   \end{itemize}
 238 \end{frame}
 239
 240 \begin{frame}{Selected African cross-coalescence rate/Population Size}
 241   \begin{center}
 242     \includegraphics[width=0.5\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/fig2a.png}
 243     \includegraphics[width=0.5\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/fig2d.png}
 244   \end{center}
 245   \begin{itemize}
 246   \item Separation began around 200 kya for present-day hunter-gatherers
 247   \item Shared ancestors as recently as 100 kya
 248   \end{itemize}
 249 \end{frame}
 250
 251 \begin{frame}{Central African rainforest hunter-gatherer}
 252   \begin{center}
 253     \includegraphics[width=0.5\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/fig2b.png}
 254     \includegraphics[width=0.5\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/fig2e.png}
 255   \end{center}
 256   \begin{itemize}
 257   \item Within africa separation begins around 100 kya
 258   \item Still intermixing between Biaka (CAR, DRC), Bantu, and Luhya (Western Kenya)
 259   \end{itemize}
 260 \end{frame}
 261
 262 \begin{frame}{Ancient, non-african}
 263   \begin{center}
 264     \includegraphics[width=0.5\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/fig2c.png}
 265     \includegraphics[width=0.5\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/fig2f.png}
 266   \end{center}
 267   \begin{itemize}
 268   \item Separation begins around 50 kya
 269   \end{itemize}
 270 \end{frame}
 271
 272 \begin{frame}{Best-fitting admixture Graph}
 273   \begin{center}
 274     \includegraphics[width=0.5\textwidth,height=0.8\textheight,keepaspectratio]{genome_diversity_paper/fig3.png}
 275   \end{center}
 276   \begin{itemize}
 277   \item Present day populations have negligible ancestry from an early
 278     dispersal of modern humans out of africa
 279   \end{itemize}
 280 \end{frame}
 281
 282
 283 \begin{frame}{Conclusions}
 284   \begin{itemize}
 285   \item Dispersal of human populations -- little evidence of ancestry
 286     from an early dispersal of modern humans
 287   \item Possible acceleration in the rate of mutations among non-Africans
 288   \item No evidence for species-wide selective sweeps around
 289     $\approx 50$ kya (start of modern human behavior in archaeological
 290     record) [Did not see that all pairs of modern humans shared a
 291     common ancestor $\lt 100$ kya.
 292   \item Great resource for additional variants; maybe with H3A?
 293   \item Useful for my work with ancestral trees
 294   \end{itemize}
 295 \end{frame}
 296
 297 \section*{References}
 298
 299 \begin{frame}[plain]{References}
 300   \begin{center}
 301     \mbox{}\vspace{-\baselineskip}
 302     \printbibliography[heading=none]
 303   \end{center}
 304 \end{frame}
 305
 306 \end{document}