phyC: Clustering cancer evolutionary trees

<div><p>Multi-regional sequencing provides new opportunities to investigate genetic heterogeneity within or between common tumors from an evolutionary perspective. Several state-of-the-art methods have been proposed for reconstructing cancer evolutionary trees based on multi-regional sequencing data to develop models of cancer evolution. However, there have been few studies on comparisons of a set of cancer evolutionary trees. We propose a clustering method (phyC) for cancer evolutionary trees, in which sub-groups of the trees are identified based on topology and edge length attributes. For interpretation, we also propose a method for evaluating the sub-clonal diversity of trees in the clusters, which provides insight into the acceleration of sub-clonal expansion. Simulation showed that the proposed method can detect true clusters with sufficient accuracy. Application of the method to actual multi-regional sequencing data of clear cell renal carcinoma and non-small cell lung cancer allowed for the detection of clusters related to cancer type or phenotype. phyC is implemented with R(≥3.2.2) and is available from <a href="https://github.com/ymatts/phyC" target="_blank">https://github.com/ymatts/phyC</a>.</p></div

<i>C</i>. <i>elegans</i> can respond to cancer cell culture medium and cancer tissue, and detect cancer smells in human urine.

<p>(A) Chemotaxis of wild-type <i>C</i>. <i>elegans</i> to 10^-6 and 10^-7 dilutions of MEM, EMEM or RPMI medium only, or culture medium from fibroblast (KMST-6 and CCD-112CoN), colorectal cancer (SW480, COLO201 and COLO205), breast cancer (MCF7) or gastric cancer (NUGC4, MKN1 and MKN7) cells (n ≥ 5 assays). (B) Chemotaxis of wild type and <i>odr-3</i> mutants (n ≥ 5 assays) in response to a 10^-6 dilution of conditioned culture medium from colorectal, breast or gastric cancer cells. (C) Chemotaxis of wild type to 10^-2, 10^-3 and 10^-4 dilutions of saline with normal and cancer tissue (n ≥ 5 assays). (D) Chemotaxis to normal and cancer tissue by wild-type and <i>odr-3</i> mutants (n ≥ 5 assays). (E) Chemotaxis of wild type to human urine samples from control subjects (blue bars; c1–c10) or cancer patients (orange bars; p1–p20) at 10^-1 dilution (n = 5 assays). (F) Chemotaxis to urine from cancer patients by wild-type and <i>odr-3</i> mutants at 10^-1 dilution (n ≥ 6 assays). Error bars represent SEM. Significant differences from control samples are indicated by * (<i>P</i> < 0.05); ** (<i>P</i> < 0.01); *** (<i>P</i> < 0.001) by Dunnett’s tests (A) or Student’s <i>t</i>-tests (B, C, D, F). † indicates a significant difference (<i>P</i> < 0.05) by Student’s <i>t</i>-tests (A).</p

NSDT of 242 urine samples.

<p>Box plots (A) and dot plots (B) of chemotactic responses of wild-type <i>C</i>. <i>elegans</i> to urine samples from control subjects (n = 218) or cancer patients (n = 24). Whiskers indicate 10th and 90th percentiles.</p

A Highly Accurate Inclusive Cancer Screening Test Using <i>Caenorhabditis elegans</i> Scent Detection

<div><p>Early detection and treatment are of vital importance to the successful eradication of various cancers, and development of economical and non-invasive novel cancer screening systems is critical. Previous reports using canine scent detection demonstrated the existence of cancer-specific odours. However, it is difficult to introduce canine scent recognition into clinical practice because of the need to maintain accuracy. In this study, we developed a Nematode Scent Detection Test (NSDT) using <i>Caenorhabditis elegans</i> to provide a novel highly accurate cancer detection system that is economical, painless, rapid and convenient. We demonstrated wild-type <i>C</i>. <i>elegans</i> displayed attractive chemotaxis towards human cancer cell secretions, cancer tissues and urine from cancer patients but avoided control urine; in parallel, the response of the olfactory neurons of <i>C</i>. <i>elegans</i> to the urine from cancer patients was significantly stronger than to control urine. In contrast, G protein α mutants and olfactory neurons-ablated animals were not attracted to cancer patient urine, suggesting that <i>C</i>. <i>elegans</i> senses odours in urine. We tested 242 samples to measure the performance of the NSDT, and found the sensitivity was 95.8%; this is markedly higher than that of other existing tumour markers. Furthermore, the specificity was 95.0%. Importantly, this test was able to diagnose various cancer types tested at the early stage (stage 0 or 1). To conclude, <i>C</i>. <i>elegans</i> scent-based analyses might provide a new strategy to detect and study disease-associated scents.</p></div