ADD sr figure and nmr cor figure
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@ -2309,14 +2309,25 @@ three methods. Lastly, SR and PLSR achieved R2>90\% while other ML methods
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exhibited exceedingly variable LOO-R2 (0.3\%,RF-51.5\%,LASSO) for CD8+ TN+TCM
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exhibited exceedingly variable LOO-R2 (0.3\%,RF-51.5\%,LASSO) for CD8+ TN+TCM
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cells.
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cells.
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% FIGURE the CD4/CD8 model results using SR
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\begin{figure*}[ht!]
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\begingroup
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\includegraphics{../figures/sr_omics.png}
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\endgroup
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\caption[Symbolic Regression Cytokine Dependencies]
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{Multi-omics culturing media prediction profiles at day 6 using symbolic
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regression.}
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\label{fig:sr_omics}
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\end{figure*}
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The top-performing technique, SR, showed that the median aggregated predictions
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The top-performing technique, SR, showed that the median aggregated predictions
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for CD4+ and CD8+ TN+TCM cells increases when IL2 concentration, IL15, and IL2R
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for CD4+ and CD8+ TN+TCM cells increases when IL2 concentration, IL15, and IL2R
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increase while IL17a decreases in conjunction with other features. These
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increase while IL17a decreases in conjunction with other features. These
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patterns combined with low values of DMS concentration and GM-CSF uniquely
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patterns combined with low values of DMS concentration and GM-CSF uniquely
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characterized maximum CD8+ TN+TCM. Meanwhile, higher glycine but lower IL13 in
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characterized maximum CD8+ TN+TCM. Meanwhile, higher glycine but lower IL13 in
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combination with others showed maximum CD4+ TN+TCM predictions (Fig.2).
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combination with others showed maximum CD4+ TN+TCM predictions
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(\cref{fig:sr_omics}).
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\begin{figure*}[ht!]
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\begin{figure*}[ht!]
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\begingroup
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\begingroup
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@ -2345,6 +2356,30 @@ concentration, were commonly selected in >=5 ML methods (Fig.3a,c). Moreover,
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IL13 and IL15 were found predictive in combination with these using SR
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IL13 and IL15 were found predictive in combination with these using SR
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(Supp.Table.S4).
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(Supp.Table.S4).
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\begin{figure*}[ht!]
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\begingroup
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\includegraphics{../figures/nmr_cors.png}
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\phantomsubcaption\label{fig:nmr_cors_lactate}
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\phantomsubcaption\label{fig:nmr_cors_formate}
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\phantomsubcaption\label{fig:nmr_cors_glucose}
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\phantomsubcaption\label{fig:nmr_cors_matrix}
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\endgroup
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\caption[NMR Day 4 correlations]
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{\gls{nmr} features at day 4 are strongly correlated with each other and the
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response variables. Highly correlated relationships are shown for
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\subcap{fig:nmr_cors_lactate}{lactate},
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\subcap{fig:nmr_cors_formate}{formate}, and
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\subcap{fig:nmr_cors_glucose}{glucose}. Blue and blue connections indicate
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positive and negative correlations respectively. The threshold for
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visualizing connections in all cases was 0.8.
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\subcap{fig:nmr_cors_matrix}{The correlation matrix for all predictive
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features and the total \ptmemh{} response.}
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}
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\label{fig:nmr_cors}
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\end{figure*}
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\section{discussion}
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\section{discussion}
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% optimization of process features
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% optimization of process features
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@ -2384,8 +2419,8 @@ features were observed to slightly improve prediction and dominated the ranking
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of important features and variable combinations when modeling together with NMR
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of important features and variable combinations when modeling together with NMR
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media analysis and process parameters (Fig.3b,d).
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media analysis and process parameters (Fig.3b,d).
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Predictive cytokine features such as \gls{tnfa}, IL2R, IL4, IL17a, IL13, and IL15 were
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Predictive cytokine features such as \gls{tnfa}, IL2R, IL4, IL17a, IL13, and
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biologically assessed in terms of their known functions and activities
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IL15 were biologically assessed in terms of their known functions and activities
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associated with T cells. T helper cells secrete more cytokines than T cytotoxic
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associated with T cells. T helper cells secrete more cytokines than T cytotoxic
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cells, as per their main functions, and activated T cells secrete more cytokines
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cells, as per their main functions, and activated T cells secrete more cytokines
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than resting T cells. It is possible that some cytokines simply reflect the
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than resting T cells. It is possible that some cytokines simply reflect the
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@ -2423,8 +2458,6 @@ ability to induce large numbers of memory T cells by functioning in an
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autocrine/paracrine manner and could be explored by blocking either the cytokine
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autocrine/paracrine manner and could be explored by blocking either the cytokine
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or its receptor.
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or its receptor.
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% FIGURE correlation plots from supplement (as alluded to here)
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Moreover, many predictive metabolites found here are consistent with metabolic
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Moreover, many predictive metabolites found here are consistent with metabolic
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activity associated with T cell activation and differentiation, yet it is not
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activity associated with T cell activation and differentiation, yet it is not
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clear how the various combinations of metabolites relate with each other in a
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clear how the various combinations of metabolites relate with each other in a
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