Estrogen responding genes per state.

<p>Among the entire gene set considered in the MCF-7 cell experiment, 1270 also responded in ZR-75.1 cells. These are referred to as common ‘estrogen-regulated genes’ (E2R genes) in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088485#pone.0088485-Cicatiello1" target="_blank">[4]</a>. ‘Primary genes’ are their subgroup having a ER transcription factor binding site within 10 kb around the TSS. The figures show how E2R and primary genes are responding across the single-cell states of a six-state model. (<b>A</b>) Fraction of up-regulated and down-regulated E2R genes. (<b>B</b>) Fraction of first-responding E2R genes, i.e., of genes that respond for the first time in a given state. (<b>C</b>) and (<b>D</b>) show the analogous pattern of primary genes.</p

The number of single-cell states in the MCF-7 response to estrogen.

<p>(<b>A</b>) The mean squared error of the model fit to the microarray data decreases as function of the number of states: as expected, when the number of parameters increases, the quality of the fit improves. (<b>B</b>) The condition number is a measure of the similarity of the transcriptional profiles of the states. It increases as function of the number of states, , highlighting that over-fitting also increases with . A good balance between fit quality and over-fitting must be found. (<b>C</b>) The model posterior probability, derived by a Bayesian approach, has a peak at , which shows that a model with six states strikes a good balance between fit-to-data and model parsimony.</p

The single-cell transition rates in the ZR-75.1 system.

<p>Results of the six-state model for time course data in hormone-starved ZR-75.1 cells responding to estrogen stimulation are shown for comparison with the MCF-7 system of <b>Fig. 3</b>. (<b>A</b>) Cell population dynamics. (<b>B</b>) Rates and mean times of transitions. In ZR-75.1 the response to estrogen is initially one order of magnitude faster than in MCF-7.</p

Marker genes in the MCF-7 system.

<p>In each state of a six-state model, genes are ranked by their state-expression fold change with respect to the first state. Here, only the top 50 are shown along with their ranking in the other states. For the top genes of state 2 also the rank assigned considering a maximum fold change criterion over the time course is shown for comparison (separated column). The state-based ranking criterion highlights marker genes which would otherwise pass unnoticed.</p

Fits to gene expression time-course data.

<p>The fit to some key genes, comprising the 11 primary transcription factors identified by Cicatiello et<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088485#pone.0088485-Cicatiello1" target="_blank">[4]</a> and other important estrogen-responsive genes <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088485#pone.0088485-Zhu1" target="_blank">[1]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088485#pone.0088485-Weisz1" target="_blank">[2]</a>, are shown: black circles represent time-course (standardized) data while green lines represents the gene expression predicted by the six-state model.</p