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More or less-On the influence of labelling strategies to infer cell population dynamics.

ABSTRACT: The adoptive transfer of labelled cell populations has been an essential tool to determine and quantify cellular dynamics. The experimental methods to label and track cells over time range from fluorescent dyes over congenic markers towards single-cell labelling techniques, such as genetic barcodes. While these methods have been widely used to quantify cell differentiation and division dynamics, the extent to which the applied labelling strategy actually affects the quantification of the dynamics has not been determined so far. This is especially important in situations where measurements can only be obtained at a single time point, as e.g. due to organ harvest. To this end, we studied the appropriateness of various labelling strategies as characterised by the number of different labels and the initial number of cells per label to quantify cellular dynamics. We simulated adoptive transfer experiments in systems of various complexity that assumed either homoeostatic cellular turnover or cell expansion dynamics involving various steps of cell differentiation and proliferation. Re-sampling cells at a single time point, we determined the ability of different labelling strategies to recover the underlying kinetics. Our results indicate that cell transition and expansion rates are differently affected by experimental shortcomings, such as loss of cells during transfer or sampling, dependent on the labelling strategy used. Furthermore, uniformly distributed labels in the transferred population generally lead to more robust and less biased results than non-equal label sizes. In addition, our analysis indicates that certain labelling approaches incorporate a systematic bias for the identification of complex cell expansion dynamics.

SUBMITTER: Gabel M

PROVIDER: S-EPMC5646766 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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More or less-On the influence of labelling strategies to infer cell population dynamics.

Gabel Michael M Regoes Roland R RR Graw Frederik F

PloS one 20171018 10

The adoptive transfer of labelled cell populations has been an essential tool to determine and quantify cellular dynamics. The experimental methods to label and track cells over time range from fluorescent dyes over congenic markers towards single-cell labelling techniques, such as genetic barcodes. While these methods have been widely used to quantify cell differentiation and division dynamics, the extent to which the applied labelling strategy actually affects the quantification of the dynamic ...[more]

PMID: 29045427

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Project description:Implantable chemoport is a very useful device for long-term venous access for infusion of chemotherapeutic drugs and other agents. There are few studies from resource poor countries reporting complications of chemoport. The aim of the present study is to evaluate the feasibility of chemoport insertion without image guidance and by closed technique without direct visualisation of a major vein (mainly IJV) and to study the complications associated with the procedure. This was a prospective observational study which analysed 263 patients who underwent chemoport insertion. The medical records of these patients were analysed for the patient characteristics, diagnosis, port-related complications, and their management. A total of 263 patients who were harbouring either locoregionally advanced or metastatic tumour requiring either chemotherapy or targeted treatment or both were included in the study. In total, 133 (50.57%) were female patients and 130 were male patients (49.43%). A total of 236 patients (89.73%) underwent port insertion procedures under local anaesthesia. None of the patients had any major intra-operative complications. Postoperatively, 4 patients (1.52%) were found to have port catheter malposition; 3 out of this 4 were corrected under IITV guidance as a second procedure under local anaesthesia only. One patient (0.38%) required formal removal and replacement of port. Four patients (1.52%) developed IJV thrombosis requiring port removal and anti-coagulation. One patient (0.38%) developed thrombus in the right atrium. There were 2 port site infections (0.74%) requiring port removal (SSI cat. 5). Low complication rates of port insertion were observed in the present, large, prospective study. Complication rates may be further reduced by using a well-designed procedure, experienced surgeons, an aseptic environment, ultrasound-guided puncture, and fluoroscopy with contrast media.Supplementary informationThe online version contains supplementary material available at 10.1007/s13193-020-01265-6.

Project description:BackgroundSupertree methods combine phylogenies with overlapping sets of taxa into a larger one. Topological conflicts frequently arise among source trees for methodological or biological reasons, such as long branch attraction, lateral gene transfers, gene duplication/loss or deep gene coalescence. When topological conflicts occur among source trees, liberal methods infer supertrees containing the most frequent alternative, while veto methods infer supertrees not contradicting any source tree, i.e. discard all conflicting resolutions. When the source trees host a significant number of topological conflicts or have a small taxon overlap, supertree methods of both kinds can propose poorly resolved, hence uninformative, supertrees.ResultsTo overcome this problem, we propose to infer non-plenary supertrees, i.e. supertrees that do not necessarily contain all the taxa present in the source trees, discarding those whose position greatly differs among source trees or for which insufficient information is provided. We detail a variant of the PhySIC veto method called PhySIC_IST that can infer non-plenary supertrees. PhySIC_IST aims at inferring supertrees that satisfy the same appealing theoretical properties as with PhySIC, while being as informative as possible under this constraint. The informativeness of a supertree is estimated using a variation of the CIC (Cladistic Information Content) criterion, that takes into account both the presence of multifurcations and the absence of some taxa. Additionally, we propose a statistical preprocessing step called STC (Source Trees Correction) to correct the source trees prior to the supertree inference. STC is a liberal step that removes the parts of each source tree that significantly conflict with other source trees. Combining STC with a veto method allows an explicit trade-off between veto and liberal approaches, tuned by a single parameter.Performing large-scale simulations, we observe that STC+PhySIC_IST infers much more informative supertrees than PhySIC, while preserving low type I error compared to the well-known MRP method. Two biological case studies on animals confirm that the STC preprocess successfully detects anomalies in the source trees while STC+PhySIC_IST provides well-resolved supertrees agreeing with current knowledge in systematics.ConclusionThe paper introduces and tests two new methodologies, PhySIC_IST and STC, that demonstrate the interest in inferring non-plenary supertrees as well as preprocessing the source trees. An implementation of the methods is available at: http://www.atgc-montpellier.fr/physic_ist/.

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More or less-On the influence of labelling strategies to infer cell population dynamics.

Publications

More or less-On the influence of labelling strategies to infer cell population dynamics.

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