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\title[Simons Genome Div.]{Simons Genome Diversity Project}
\author[Don Armstrong]{Don L. Armstrong}
\institute[IGB]{Institute for Genomic Biology, Computing Genomes 
  for Reproductive Health, University of Illinois, Urbana-Champaign}

\begin{document}

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library("data.table")
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library("reshape2")
library("grid")
library("xtable")

@ 

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  \begin{center}
    Code and slides are here: 
    
    \qrcode[padding]{http://dla2.us/p/genomdiv2016}
    
    \url{http://dla2.us/p/genomdiv2016}
   \end{center}
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\frame[plain]{
   \begin{center}
     \includegraphics[width=\textwidth,height=0.8\textheight,keepaspectratio]{genome_diversity_paper/title.png}
   \end{center}
}

\begin{frame}{Sampling}
  \begin{itemize}
  \item 142 populations from Africa, America, Oceania, South Asia,
    East Asia, and West Eurasia (mostly indigenous)
  \item 300 samples sequenced at 34-83 fold coverage by Illumina
  \item Aligned using BWA-MEM
  \item Genotyped using special version of GATK and Fermikit
  \item Data available in EBI ($n=279$, PRJEB9586) and dbGAP ($n=21$, ?)
  \end{itemize}
\end{frame}


\begin{frame}[fragile]{Alignment Pipeline}
  \begin{itemize}
  \item Aligned to the “decoy” version of the human reference
    (hs37d5); supposedly improves alignment in misassembled regions or
    regions with CNVs?
  \item PCR-free data, though they marked optical duplicates marked
    using samblaster
  \end{itemize}
\begin{minted}{bash}
./htscmd bamshuf -Oun128 in.bam tmp-pre \
| ./htscmd bam2fq -as aln-se.fq.gz - \
| ./trimadap \
| ./bwa mem -pt8 hs37d5.fa - \
| ./samblaster \
| samtools view -uS - \
| samtools sort -@4 -m512M - out-pre
\end{minted}
\end{frame}

\begin{frame}[fragile]{Genotyping}
  \begin{itemize}
  \item Reference-bias; novel variants, GATK assumes reference is more
    likely which may not be the case. Use prior of
    $(0.4995,0.001,0.4995)$ instead of default
    $(0.9985,0.001,0.0005)$.
    \begin{itemize}
    \item Unclear what the effect of this change is on the calling
    \item Maybe worth thinking about?
    \end{itemize}
  \item Also used Fermikit; apparently has comparable call rates to
    GATK and platypus
  \end{itemize}
\begin{minted}{bash}
  java -Xmx2g -jar GenomeAnalysisTK.jar \
  -T UnifiedGenotyper -I srt.aln.bam \
  -L CHR_ID -R hs37d5.fa -dcov 600 -glm SNP \
  -out_mode EMIT_ALL_SITES -stand_call_conf 5.0 \
  -stand_emit_conf 5.0 -inputPrior 0.0010 \
  -inputPrior 0.4995 -D dbsnp_138.b37.vcf \
  -o CHR_ID.vcf -A GCContent -A BaseCounts
\end{minted}
\end{frame}

\begin{frame}{Fermikit vs Platypus vs GATK}
  \begin{columns}
    \column{0.5\textwidth}
    \includegraphics[width=\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/supplemental-014.png}
    \column{0.5\textwidth}
  FermiKit and Platypus call 3.17M more sites than GATK, but unclear
  whether those are real sites or not; they go into this in much more
  detail than I've digested yet.
\end{columns}
\end{frame}

\begin{frame}{Relatedness of Populations}
  \begin{columns}
    \column{0.7\textwidth}
    \includegraphics[width=0.5\textwidth,height=0.8\textheight,keepaspectratio]{genome_diversity_paper/fig1a_1.png}
    \includegraphics[width=0.5\textwidth,height=0.8\textheight,keepaspectratio]{genome_diversity_paper/fig1a_2.png}
    \column{0.3\textwidth}
    \begin{itemize}
    \item Neighbor joining tree based on pairwise divergence per nucleotide
    \item Deepest splits are in African populations
    \end{itemize}
  \end{columns}
\end{frame}

\begin{frame}{PCA and Relatedness}
  \begin{center}
    \includegraphics[width=\textwidth,height=0.6\textheight,keepaspectratio]{genome_diversity_paper/fig_ed4.png}
  \end{center}
  \begin{itemize}
  \item Greatest variation seen in the African populations (orange)
  \item Other populations are much more similar to eachother in
    general
  \item Hapmap likely under-measured variation in Africa
  \end{itemize}
\end{frame}

\begin{frame}
  \begin{center}
    \includegraphics[width=\textwidth,height=0.6\textheight,keepaspectratio]{genome_diversity_paper/fig1b.png}
  \end{center}
  \begin{itemize}
  \item Pygmy populations have lower X heterozygosity than other African populations
  \item Seen even after removing the third of X which is subject to selection
  \item Suggests that it's driven by demographic history, and the
    reduced diversity is due to male-driven admixture (also in non-Africans)
  \end{itemize}
\end{frame}

\begin{frame}{Neanderthal Ancestry}
  \begin{center}
    \includegraphics[width=\textwidth,height=0.6\textheight,keepaspectratio]{genome_diversity_paper/fig1c.png}
  \end{center}
  \begin{itemize}
  \item No populations studied have a higher Neanderthal ancestry than
    East Asians
  \end{itemize}
\end{frame}

\begin{frame}{Denisovan Ancestry}
  \begin{center}
    \includegraphics[width=\textwidth,height=0.6\textheight,keepaspectratio]{genome_diversity_paper/fig1d.png}
  \end{center}
  \begin{itemize}
  \item Oceanian groups have as much as 5\% Denisovan ancestry
  \item Eurasian differences in ancestry; some South Asians may have
    higher Denisovan than other Eurasians
  \end{itemize}
\end{frame}
g

\begin{frame}{Variation missed by hapmap}
  \begin{center}
    \includegraphics[width=\textwidth,height=0.8\textheight,keepaspectratio]{genome_diversity_paper/fig_ed1.png}
  \end{center}
  \begin{itemize}
  \item Hapmap is missing up to 8\% of the heterozygous sites in parts
    of Africa
  \end{itemize}
\end{frame}

\begin{frame}{Selected African cross-coalescence rate/Population Size}
  \begin{center}
    \includegraphics[width=0.5\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/fig2a.png}
    \includegraphics[width=0.5\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/fig2d.png}
  \end{center}
  \begin{itemize}
  \item Separation began around 200 kya for present-day hunter-gatherers
  \item Shared ancestors as recently as 100 kya
  \end{itemize}
\end{frame}

\begin{frame}{Central African rainforest hunter-gatherer}
  \begin{center}
    \includegraphics[width=0.5\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/fig2b.png}
    \includegraphics[width=0.5\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/fig2e.png}
  \end{center}
  \begin{itemize}
  \item Within africa separation begins around 100 kya
  \item Still intermixing between Biaka (CAR, DRC), Bantu, and Luhya (Western Kenya)
  \end{itemize}
\end{frame}

\begin{frame}{Ancient, non-african}
  \begin{center}
    \includegraphics[width=0.5\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/fig2c.png}
    \includegraphics[width=0.5\textwidth,height=0.7\textheight,keepaspectratio]{genome_diversity_paper/fig2f.png}
  \end{center}
  \begin{itemize}
  \item Separation begins around 50 kya
  \end{itemize}
\end{frame}

\begin{frame}{Best-fitting admixture Graph}
  \begin{center}
    \includegraphics[width=0.5\textwidth,height=0.8\textheight,keepaspectratio]{genome_diversity_paper/fig3.png}
  \end{center}
  \begin{itemize}
  \item Present day populations have negligible ancestry from an early
    dispersal of modern humans out of africa
  \end{itemize}
\end{frame}


\begin{frame}{Conclusions}
  \begin{itemize}
  \item Dispersal of human populations -- little evidence of ancestry
    from an early dispersal of modern humans
  \item Possible acceleration in the rate of mutations among non-Africans
  \item No evidence for species-wide selective sweeps around
    $\approx 50$ kya (start of modern human behavior in archaeological
    record) [Did not see that all pairs of modern humans shared a
    common ancestor $\lt 100$ kya.
  \item Great resource for additional variants; maybe with H3A?
  \item Useful for my work with ancestral trees
  \end{itemize}
\end{frame}

\section*{References}

\begin{frame}[plain]{References}
  \begin{center}
    \mbox{}\vspace{-\baselineskip}
    \printbibliography[heading=none]
  \end{center}
\end{frame}

\end{document}