diff --git a/figures/nmr_cors.svg b/figures/nmr_cors.svg new file mode 100644 index 0000000..e865a86 --- /dev/null +++ b/figures/nmr_cors.svg @@ -0,0 +1,12458 @@ + + + + + + + + + + + + + + + + + + + + + + image/svg+xml + + + + + + + + + + a. + b. + c. + d. + + diff --git a/figures/sr_omics.svg b/figures/sr_omics.svg new file mode 100644 index 0000000..4ef2ebd --- /dev/null +++ b/figures/sr_omics.svg @@ -0,0 +1,8539 @@ + + + + + + + + + + + + image/svg+xml + + + + + + + + diff --git a/tex/thesis.tex b/tex/thesis.tex index c732626..154331b 100644 --- a/tex/thesis.tex +++ b/tex/thesis.tex @@ -2309,14 +2309,25 @@ three methods. Lastly, SR and PLSR achieved R2>90\% while other ML methods exhibited exceedingly variable LOO-R2 (0.3\%,RF-51.5\%,LASSO) for CD8+ TN+TCM cells. -% FIGURE the CD4/CD8 model results using SR +\begin{figure*}[ht!] + \begingroup + + \includegraphics{../figures/sr_omics.png} + + \endgroup + \caption[Symbolic Regression Cytokine Dependencies] + {Multi-omics culturing media prediction profiles at day 6 using symbolic + regression.} + \label{fig:sr_omics} +\end{figure*} The top-performing technique, SR, showed that the median aggregated predictions for CD4+ and CD8+ TN+TCM cells increases when IL2 concentration, IL15, and IL2R increase while IL17a decreases in conjunction with other features. These patterns combined with low values of DMS concentration and GM-CSF uniquely characterized maximum CD8+ TN+TCM. Meanwhile, higher glycine but lower IL13 in -combination with others showed maximum CD4+ TN+TCM predictions (Fig.2). +combination with others showed maximum CD4+ TN+TCM predictions +(\cref{fig:sr_omics}). \begin{figure*}[ht!] \begingroup @@ -2345,6 +2356,30 @@ concentration, were commonly selected in >=5 ML methods (Fig.3a,c). Moreover, IL13 and IL15 were found predictive in combination with these using SR (Supp.Table.S4). +\begin{figure*}[ht!] + \begingroup + + \includegraphics{../figures/nmr_cors.png} + \phantomsubcaption\label{fig:nmr_cors_lactate} + \phantomsubcaption\label{fig:nmr_cors_formate} + \phantomsubcaption\label{fig:nmr_cors_glucose} + \phantomsubcaption\label{fig:nmr_cors_matrix} + + \endgroup + \caption[NMR Day 4 correlations] + {\gls{nmr} features at day 4 are strongly correlated with each other and the + response variables. Highly correlated relationships are shown for + \subcap{fig:nmr_cors_lactate}{lactate}, + \subcap{fig:nmr_cors_formate}{formate}, and + \subcap{fig:nmr_cors_glucose}{glucose}. Blue and blue connections indicate + positive and negative correlations respectively. The threshold for + visualizing connections in all cases was 0.8. + \subcap{fig:nmr_cors_matrix}{The correlation matrix for all predictive + features and the total \ptmemh{} response.} + } + \label{fig:nmr_cors} +\end{figure*} + \section{discussion} % optimization of process features @@ -2384,8 +2419,8 @@ features were observed to slightly improve prediction and dominated the ranking of important features and variable combinations when modeling together with NMR media analysis and process parameters (Fig.3b,d). -Predictive cytokine features such as \gls{tnfa}, IL2R, IL4, IL17a, IL13, and IL15 were -biologically assessed in terms of their known functions and activities +Predictive cytokine features such as \gls{tnfa}, IL2R, IL4, IL17a, IL13, and +IL15 were biologically assessed in terms of their known functions and activities associated with T cells. T helper cells secrete more cytokines than T cytotoxic cells, as per their main functions, and activated T cells secrete more cytokines than resting T cells. It is possible that some cytokines simply reflect the @@ -2423,8 +2458,6 @@ ability to induce large numbers of memory T cells by functioning in an autocrine/paracrine manner and could be explored by blocking either the cytokine or its receptor. -% FIGURE correlation plots from supplement (as alluded to here) - Moreover, many predictive metabolites found here are consistent with metabolic activity associated with T cell activation and differentiation, yet it is not clear how the various combinations of metabolites relate with each other in a