\documentclass[12pt]{gsasthesis} % 10,11 and 12pt fonts allowed

%%%%%%%%%%%%%%%% PACKAGES USED BY WILL TOWNES %%%%%%%%%%%%%%%%
\usepackage{amssymb}
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\usepackage{lmodern}
\usepackage{textcomp}
\usepackage{adjustbox}
\PassOptionsToPackage{hyphens}{url}\usepackage{hyperref}
\usepackage{csvsimple}

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\usepackage{etex} % extend the number of registers

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\usepackage[margin={1.2in}]{geometry}
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% \usepackage[top=1in,bottom=1.5in,left=1in,right=1.5in,twoside]{geometry} The
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% \usepackage[top=1in,left=1in,vmarginratio=2:3,hmarginratio=2:5,twoside]{geometry}

% Appendix package. Not necessary, but it does make managing appendices easier
\usepackage[titletoc]{appendix}

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%\usepackage{rotating}

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%%%%%%%%%%%%%%%% COMPULSORY FIELDS %%%%%%%%%%%%%%%%

\title{Methods for Single Cell and Longevity Genomics} % needs to match title on DAC
\author{Frederick William Townes V} % full name as it appears on your GSAS record, needs
                          % to match name on DAC
\degreename{Doctor of Philosophy}
\degreefield{Biostatistics} % Official name of subject as listed in GSAS
                                % handbook
\department{The Department of Biostatistics} % official name of department
\degreemonth{May} % Month of Defense (i.e. month when DAC was signed)
\degreeyear{2019} % Year the DAC was signed
\principaladvisor{Professor Rafael Irizarry}

%%%%%%%%%%%%%%%% Operators used by Will Townes %%%%%%%%%%%%%%%%
\newcommand{\citep}{\cite}
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\urlstyle{same}

\begin{document}

\includepdf{Townes-Will-DAC.pdf}
\null
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\pagenumbering{roman} % GSAS wants roman page numbers for frontmatter


% the following four pages are required in that order. The first two pages are
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\addcontentsline{toc}{section}{Title page}
\thesistitlepage
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\begin{abstract}
Chapter 1: Single cell RNA-Seq (scRNA-Seq) profiles gene expression of individual cells. Recent scRNA-Seq datasets have incorporated unique molecular identifiers (UMIs). Using negative controls, we show UMI counts follow multinomial sampling with no zero-inflation. Current normalization procedures such as log of counts per million and feature selection by highly variable genes produce false variability in dimension reduction. We propose simple multinomial methods, including generalized principal component analysis (GLM-PCA) for non-normal distributions, and feature selection using deviance. These methods outperform current practice in a downstream clustering assessment using ground-truth datasets.

Chapter 2: For scRNA-Seq data lacking UMIs, we propose quasi UMIs: quantile normalization of read counts to a compound Poisson distribution empirically derived from UMI datasets. In an assessment using datasets for which both UMIs and read counts were available, quasi UMIs counts were closer to UMI counts than competing normalization methods such as census counts.

Chapter 3: Aging is a complex process with poorly understood genetic mechanisms. Recent studies have sought to classify genes as pro-longevity or anti-longevity using a variety of machine learning algorithms. However, assessments based on held-out test data are lacking. Further, it is not clear which types of features are best for improving classification accuracy and precision. Leveraging gene annotations for two model organisms from the GenAge database, we use gene ontology and publicly available gene expression datasets as features to systematically compare five popular classification algorithms. Elastic net regularized logistic regression (GLM-Net) performs well. Using GLM-Net, we make predictions for pro- and anti-longevity genes among those not found in GenAge.
\end{abstract}

% Center headings for table of contents, LOT, and LOF and make them smaller so
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% if you want the default. If you want more control, use the "tocloft" package.
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\renewcommand{\listtablename}{\protect\centering\protect\Large List of Tables}
\renewcommand{\listfigurename}{\protect\centering\protect\Large List of Figures}

%force include toc page in toc
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\tableofcontents % Table of contents

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% acknowledgement is optional. Comment out whatever you don't like
\listoftables
\listoffigures
\begin{acknowledgments}
  \input{thanks}
\end{acknowledgments}
%force include copyright page in toc
\addcontentsline{toc}{section}{Dedication}
\begin{dedication}
  To my wife, Tina
\end{dedication}


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\pagenumbering{arabic} % reset page numbering and switch to arabic

% Introductory chapter. Comment out if you don't have an intro chapter, but I
% think most committees expect you to have one.
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%\addcontentsline{toc}{chapter}{Introduction}
%\chapter*{Introduction}\label{ch:intro}
%\input{intro}

\chapter[Feature Selection and Dimension Reduction for Single Cell RNA-Seq based on a Multinomial Model] {Feature Selection and Dimension Reduction for Single Cell RNA-Seq based on a Multinomial Model\footnote{Co-authored with Stephanie Hicks, Martin Aryee, and Rafael Irizarry}}\label{ch:1}
\input{chapter1}

\chapter[Quantile Normalization of Single Cell RNA-Seq Read Counts without Unique Molecular Identifiers] {Quantile Normalization of Single Cell RNA-Seq Read Counts without Unique Molecular Identifiers\footnote{Co-authored with Rafael Irizarry}}\label{ch:2}
\input{chapter2}

\chapter[Identifying pro-longevity genes by integrating gene expression and curated annotations]{Identifying pro-longevity genes by integrating gene expression and curated annotations\footnote{Co-authored with Jeffrey Miller}}\label{ch:3}
\input{chapter3}

%%%%%%%%%%%%%%%% BACK MATTER %%%%%%%%%%%%%%%%

% Put appendices, bibliography, and supplemental materials here

% The bibliography may be single spaced within each entry, but must be
% double-spaced between each entry. Most bibliography styles leave space between
% entries, so that shouldn't be a problem.
\begin{singlespacing}
  % I like "References" better than "Bibliography"
  \renewcommand{\bibname}{References}
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  %\bibliography{references}
  \bibliography{/Users/townesf/Library/texmf/bibtex/bib/Zotero}
\end{singlespacing}

% Appendices from all chapters should go at the end
%\input{appendix}

\end{document}
