Abstract
BackgroundThe increased availability of high-throughput datasets has revealed a need for reproducible and accessible analyses which can quantitatively relate molecular changes to phenotypic behavior. Existing tools for quantitative analysis generally require expert knowledge.ResultsCellPD (cell phenotype digitizer) facilitates quantitative phenotype analysis, allowing users to fit mathematical models of cell population dynamics without specialized training. CellPD requires one input (a spreadsheet) and generates multiple outputs including parameter estimation reports, high-quality plots, and minable XML files. We validated CellPD’s estimates by comparing it with a previously published tool (cellGrowth) and with Microsoft Excel’s built-in functions. CellPD correctly estimates the net growth rate of cell cultures and is more robust to data sparsity than cellGrowth. When we tested CellPD’s usability, biologists (without training in computational modeling) ran CellPD correctly on sample data within 30 min. To demonstrate CellPD’s ability to aid in the analysis of high throughput data, we created a synthetic high content screening (HCS) data set, where a simulated cell line is exposed to two hypothetical drug compounds at several doses. CellPD correctly estimates the drug-dependent birth, death, and net growth rates. Furthermore, CellPD’s estimates quantify and distinguish between the cytostatic and cytotoxic effects of both drugs—analyses that cannot readily be performed with spreadsheet software such as Microsoft Excel or without specialized computational expertise and programming environments.ConclusionsCellPD is an open source tool that can be used by scientists (with or without a background in computational or mathematical modeling) to quantify key aspects of cell phenotypes (such as cell cycle and death parameters). Early applications of CellPD may include drug effect quantification, functional analysis of gene knockout experiments, data quality control, minable big data generation, and integration of biological data with computational models.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-016-0337-5) contains supplementary material, which is available to authorized users.
Highlights
The increased availability of high-throughput datasets has revealed a need for reproducible and accessible analyses which can quantitatively relate molecular changes to phenotypic behavior
In this article we describe some applications of Cell phenotype digitizer (CellPD) and link to its source code so the scientific community can use it and build upon it
We demonstrate some key applications of CellPD by (1) evaluating its use in cell culture quality control by comparing two cultures of the same cell line (HCT 116, a colon cancer epithelial-like cell line) grown in two different media, (2) demonstrating its utility in high content screening (HCS) experiments by calculating dose-dependent cell birth and death parameters in a simulated drug screening experiment, and (3) using CellPD to determine whether these drugs are cytostatic or cytotoxic
Summary
The increased availability of high-throughput datasets has revealed a need for reproducible and accessible analyses which can quantitatively relate molecular changes to phenotypic behavior. With the increasing availability of high-throughput microscopy and high content screening (HCS), one can measure cell counts in many different environmental contexts with high precision over several time points [3] These platforms can be used to link studies on molecular biology to observable, quantitative changes in cell behavior [4, 5]. As these experimental platforms have advanced, Juarez et al BMC Systems Biology (2016): they have allowed the generation of vast amounts of data which, in turn, require sophisticated bioinformatics tools for analysis [6]. Tools which facilitate the replication and implementation of new analyses should be used in scientific computing
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