\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Inference of metabolic fluxes in nutrient-limited continuous cultures: A
Maximum Entropy Approach with minimum information}



\author[1]{Jose Pereiro}%
\author[2]{Jorge Fernandez-de-Cossio-Diaz}%
\author[3]{Roberto Mulet}%
\affil[1]{University of Havana}%
\affil[2]{Laboratory of Physics of the Ecole Normale Supérieure}%
\affil[3]{University of Havana Faculty of Physics}%


\vspace{-1em}



  
  \date{May 22, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
The study of cellular metabolism is often hindered by limitations in the
amount of exper- imental data available. Therefore computational methods
that exploit maximally the possible measurements, and are able to
extract relevant predictions from a minimum of information are always
welcome. Maximum Entropy (ME) inference has been succesfully applied to
genome-scale models of cellular metabolism in various cell culture
contexts, yielding insights into biologically relevant properties which
are not accessible to traditional optimization based methods. Recent
data-driven studies have suggested that in chemostat cultures, the
growth rate and uptake rates of limiting nutrients are the most
informative parameters about the metabolism. In this work, we propose
the thesis that chemostat dynamics typically drives the culture towards
maximally restricted metabolic states. A practical consequence is that
experimental values of limiting up- take rates can be replaced by more
readily available measurements of metabolite concentrations in the feed
media and the steady state cell concentration. We show how these results
can be justified from a mechanistic perspective by studying simulations
of a simplified model where we test the quality of the inference, and
unveil the mechanisms defining the performance of our approach. We then
apply our method to E. coli experimental data. We evaluate the effects
of heterogeneity in chemostat cultures and its potential impact on flux
inference quality of ME and optimization based strategies. Additionally,
we evaluate the quality of the inference comparing M E to alternative
formulations that rest on a Flux Balance Analysis (F BA).%
\end{abstract}%



\sloppy


\textbf{Hosted file}

\verb`MaxEnt_EColi-1.docx`  available at \url{https://authorea.com/users/443758/articles/563131-inference-of-metabolic-fluxes-in-nutrient-limited-continuous-cultures-a-maximum-entropy-approach-with-minimum-information}

\selectlanguage{english}
\FloatBarrier
\end{document}

