Perversions with a twist

PESS acknowledges grant FCT SFRH/BD/76369/201. MHG acknowledges PTDC/CTM-BIO/6178/2014.Perversions connecting two helices with symmetric handedness are a common occurrence in nature, for example in tendrils. These defects can be found in our day life decorating ribbon gifts or when plants use tendrils to attach to a support. Perversions arise when clamped elastic filaments coil into a helical shape but have to conserve zero overall twist. We investigate whether other types of perversions exist and if they display different properties. Here we show mathematically and experimentally that a continuous range of different perversions can exist and present different geometries. Experimentally, different perversions were generated using micro electrospun fibres. Our experimental results also confirm that these perversions behave differently upon release and adopt different final configurations. These results also demonstrate that it is possible to control on demand the formation and shape of microfilaments, in particular, of electrospun fibres by using ultraviolet light.publishersversionpublishe

Cellular frustration algorithms for anomaly detection applications.

Cellular frustrated models have been developed to describe how the adaptive immune system works. They are composed by independent agents that continuously pair and unpair depending on the information that one sub-set of these agents display. The emergent dynamics is sensitive to changes in the displayed information and can be used to detect anomalies, which can be important to accomplish the immune system main function of protecting the host. Therefore, it has been hypothesized that these models could be adequate to model the immune system activation. Likewise it has been hypothesized that these models could provide inspiration to develop new artificial intelligence algorithms for data mining applications. However, computational algorithms do not need to follow strictly the immunological reality. Here, we investigate efficient implementation strategies of these immune inspired ideas for anomaly detection applications and use real data to compare the performance of cellular frustration algorithms with standard implementations of one-class support vector machines and deep autoencoders. Our results demonstrate that more efficient implementations of cellular frustration algorithms are possible and also that cellular frustration algorithms can be advantageous for semi-supervised anomaly detection applications given their robustness and accuracy

Average true positive rate for simulations for context dependent (abnormal self) discrimination.

<p>In the simulations considered for these results, both normal and abnormal configurations displayed the same number of rare ligands, although in different patterns as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0169464#pone.0169464.g003" target="_blank">Fig 3</a>. Averages accounted 100 realizations and a false positive rate of 10%. Populations with 96 T cells and partially ordered ILists with were used. From these results it is clear that the best discrimination is achieved for partially ordered ILists that maximize the number of (potentially) absent frequent LOCS in top positions. In the present case this number is 24, corresponding to the size of an ILists with all LOCS from the block presented in the abnormal self configuration. It is also clear that the larger the number of rare ligands displayed, or equivalently, the larger the number of absent frequent LOCS, the higher is the discrimination.</p

Cellular responses when ILists are specifically modified to analyse the impact of missing frequent ligands.

<p>a) the number of long lived conjugations grows exponentially when a growing number of frequent LOCS are removed from top positions in a T cell IList; b) the number of long lived conjugations grows linearly when a growing number of cells has a couple of frequent LOCS removed from their ILists top positions. In these results 100 realizations of systems with 96 cells were used.</p

Generalisation capabilities are gained when samples are changed after every short time interval, <i>T</i>_<i>S</i>.

<p>a) true positive rate for discrimination of configurations with an added rare ligand (<i>N</i>_<i>r</i> = 7) b) mean rank of the highest ranked LSCS in T cell ILists in the 200 samples used for education. These results show that ordering of ILists is best achieved when samples are changed every <i>T</i>_<i>s</i> = 50 iterations which also leads to the best discrimination. Since <i>τ</i>_<i>n</i>—the maximum conjugation duration used to eliminate T cells by negative selection—is changed only when no cell is eliminated in the last <i>W</i>_<i>τ</i> = 10000 iterations, this forces ILists to be consistent with the last 10000/50 = 200 samples.</p

Can the Immune System Perform a t-Test?

<div><p>The self-nonself discrimination hypothesis remains a landmark concept in immunology. It proposes that tolerance breaks down in the presence of nonself antigens. In strike contrast, in statistics, occurrence of nonself elements in a sample (i.e., outliers) is not obligatory to violate the null hypothesis. Very often, what is crucial is the combination of (self) elements in a sample. The two views on how to detect a change seem challengingly different and it could seem difficult to conceive how immunological cellular interactions could trigger responses with a precision comparable to some statistical tests. Here it is shown that frustrated cellular interactions reconcile the two views within a plausible immunological setting. It is proposed that the adaptive immune system can be promptly activated either when nonself ligands are detected or self-ligands occur in abnormal combinations. In particular we show that cellular populations behaving in this way could perform location statistical tests, with performances comparable to t or KS tests, or even more general data mining tests such as support vector machines or random forests. In more general terms, this work claims that plausible immunological models should provide accurate detection mechanisms for host protection and, furthermore, that investigation on mechanisms leading to improved detection in “in silico” models can help unveil how the real immune system works.</p></div

Frequency of the number of frequent LOCS of each block (I and II) on ILists above the highest ranked LSCS, before and after education (maturation).

<p>These results were obtained considering self-configurations with <i>N</i>_<i>r</i> = 6 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0169464#sec020" target="_blank">Methods</a> for other remaining simulation parameters). These results show that repertoire education balances the number of frequent LOCS of each block on ILists top positions, guaranteeing that a minimum number of frequent LOCS is always present in self-configurations.</p

Comparative analysis of average ROC curves obtained in location tests using ordered samples with 80 elements drawn from lognormal distributions for the cellular frustration model and two-sided KS-test and t-test.

<p>Insets: comparison between the lognormal distributions used to draw self-configurations (black) and abnormal configurations with deviations to either side (gray). Cellular frustration models outperform the other statistical tests.</p

Comparative analysis of average ROC curves obtained in location tests using ordered samples with 80 elements drawn from normal distributions for the cellular frustration model and two-sided KS-test and t-test.

<p>Insets: comparison between gaussian distributions used to draw self-configurations (black) and abnormal configurations with deviations to either side (gray). Similar plots would be obtained for the distributions in the bottom examples. Abnormal-distributions are only slightly displaced. The t-test is the best estimator as demonstrated in the literature for this ideal case. However, cellular frustration models give very close results.</p

Abnormal self discrimination for populations with educated ILists when the number of rare ligands displayed is varied.

<p>Increasing the number of rare ligands in self and abnormal self-configurations increases discrimination. This result agrees with the theoretical arguments developed under the more restrictive conditions of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0169464#pone.0169464.g007" target="_blank">Fig 7</a>. In particular, it shows that context information can be perfectly discriminated even when ILists are ordered by negative selection.</p