MULTIMOT

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MULTIMOT: towards anopen data ecosystem forcell migration research

paola masuzzo

@pcmasuzzocomputational omics and systems biology groupVIB / Ghent University, Ghent, Belgium

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modified from http://www.nps.gov/crmo/learn/education/activity-5a.htm

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An open data ecosystem for cell migration research can bring enormous benefits

• standardization of data and metadata is essential for reproducibility and unambiguous interpretation of experiments

• data exchange = faster and easier access to results

+ quality control

+ integration with in silico modeling

• open data = opportunities for knowledge discovery, data mining, data re-use

• formulation of new hypotheses/principles

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Local management, analysis and sharing of cell migration data

plan your migration experiment

import and store your data

explore and analyse your data

collective cell migration

single-cell migration

exchange your data

Towards a global repository for cell migration data

data and metadata standardization

data dissemination

CMSO: your input!

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exchange your data



data dissemination

CMSO: your input!

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A big challenge in cell migrationis data management and dissemination

Masuzzo, Trends in Cell Biology, 2015

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A big challenge in cell migrationis data management and dissemination


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There are four key elements to softwarefor cell migration data

Guide and capture the experimental set-up

Store, structure and query the acquired data

(Semi-)automate data exploration, analysis andinterpretation

Enable data exchange

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That’s why we developed CellMissy…

Experiment

0 3h 6h

wound

cells

Experiment Manager

DataLoader

Data Analyzer

Masuzzo, Bioinformatics, 2013 - github.com/compomics/cellmissy

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exchange your data



data dissemination

CMSO: your input!

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CellMissy helps you plan your migration/invasion experiment

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Detailed metadata annotationis essential for data interpretation

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exchange your data



data dissemination

CMSO: your input!

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Cell migration data are imported automagically

Link to raw images (ordering of imaged wells)

Imaging techniques

Exposure time, light intensity, magnification, time interval

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Structuring the data takes a bit of effort

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exchange your data



data dissemination

CMSO: your input!

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Cell migration can occur both in a collective and in a single-cell fashion

Images courtesy of group C. Ampe, UGent, tracked by CELLMIA

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This duality in cell migration modesis reflected in data analysis pipelines


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exchange your data



data dissemination

CMSO: your input!

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Automated quality control is performedwithin replicates …

%area increase

densi

ty

KERNEL DENSITY ESTIMATION

outlier

detection

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Automated quality control is performedwithin replicates …

outlier

detection

%area increase

densi

ty

KERNEL DENSITY ESTIMATION

%area increase

densi

ty

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… as well as across replicates

time (min)

Are

a (μm2)

X XX

XX

X X

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Analysis is carried out on conditions after averaging across the QC replicates

time (min)

Are

a (μm2)

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Statistical comparison has never been so easy

analysis report with graphs, tables and results

velo

city

(μm2\m

in)

median cell sheet velocity

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exchange your data



data dissemination

CMSO: your input!

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Single-cell trajectories carry a lot of information!

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Cell-centric parameters are computed on each cell and then averaged for the entire population

trajectory 1

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trajectory 1

trajectory 2

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trajectory 1

trajectory 2

trajectory 3

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trajectory 1

trajectory 2

trajectory 3

trajectory 4

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...

trajectory 1

trajectory 2

trajectory 3

trajectory 4

trajectory 5

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Step-centric parameters are aggregated values of all migration steps

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Cell-centric parameters are biased because dependent on cell trajectory length

fast moving cells tend to be associated with relatively straight trajectories, high confinement ratios and low turning angles

these cells could be seen as a distinct subpopulation

if these cells were to be visualized for a longer time, one might actually see that they do not move so fast, nor so straight

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Step-centric parameters can overlookthe presence of cell sub-populations

densi

ty

step-centric displacement cell-centric displacement

technical replicates

BT-549 cancer cells - 37.5 µM Jasplakinolide

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Step-centric parameters can overlookthe presence of cell sub-populations

MDA-MB-231 cancer cells - 3D ORIS - 0.05µM EGF

step-centric turning angle cell-centric turning angle

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CellMissy provides an analysis pipeline where both types of parameters can be computed...

acirc 2.66

direct 0.041

x (µm)

y (

µm

)

acirc 5.091

direct 0.079

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... together with ‘classical’ cell migration quantities

acirc 2.66

direct 0.041

x (µm)

y (

µm

)

acirc 5.091

direct 0.079

MSD

(µm

²)

time-lag

time-index

dir.

ratio

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Additional local properties aid the recognition of different migratory patterns

x (µm)

y (

µm

)

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exchange your data



data dissemination

CMSO: your input!

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These data support analysis on multiple levels

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exchange your data



data dissemination

CMSO: your input!

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Metadata and/or data can be easily exchanged between laboratories

lab A

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lab Blab A

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lab B

This is one file in CellMissy! (≈10 MB)

lab A

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CellMissy provides key functions for the management and analysis of cell migration data

Experimental set-up and annotation

Efficient and fully automated data

import and storage

Data inspection and analysis on multiple levels

Tools for metadata/data exchange

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exchange your data



data dissemination

CMSO: your input!

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Imagine to have a global repositoryfor cell migration data...

Data

Repository

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Imagine to have a global repositoryfor cell migration data...

Data

RepositoryLocal Software

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The need of an open data platform was shared between researchers

Cell migration workshop, Ghent, March 2014

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The objective of MULTIMOT is to buildan open data ecosystem for cell migration


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exchange your data



data dissemination

CMSO: your input!

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Such ecosystem requires standardizationof the entire workflow

Controlled

vocabularies

Minimum reporting

requirements

Data and metadata

standard formats


cell migration dataset

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Controlled

vocabularies

Minimum reporting

requirements

Data and metadata

standard formats



CC BY-SA 4.0


Controlled

vocabularies

Minimum reporting

requirements

Data and metadata

standard formats



CC BY-SA 4.0


Controlled

vocabularies

Minimum reporting

requirements

Data and metadata

standard formats



CC BY-SA 4.0







exchange your data



data dissemination

CMSO: your input!

CC BY-SA 4.0

Importantly, deposited data are not the end;an ecosystem enables re-use as well!


standard-compliant


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standard-compliant


Data

Repository

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standard-compliant


Data

Repository

global

dissemination

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standard-compliant


Data

Repository

global

dissemination

multiscale and

meta-scale

analysis

algorithms

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The integration of data from different study models would be much easier


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Mathematical modeling and numerical simulations complement in vitro research


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The integration of in vitro experimentswith in silico models would benefit

cell migration dataand new hypotheses

qualitative and

quantitative modelling

translation into a modelling language

data analysis and interpretation

wet-lab experiments (test of hypotheses)

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exchange your data



data dissemination

CMSO: your input!

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MULTIMOT pairs wet-lab scientistswith relevant BioIT researchers

Participant No Participant organisation name PI Country

1 VIB (VIB) Lennart Martens BE

2 Weizmann Institute of Science (WIS) Benjamin Geiger IL

3 Ghent University (UG) Christophe Ampe BE

4 Radboud UMC (RUMC) Peter Friedl NL

5 Karolinska Institutet (KI) Staffan Strömblad SE

6 The Chancellor, Masters and Scholars of the University of Oxford (UOXF)

Susanna-Assunta Sansone UK

7 Dundee University (DU) Jason Swedlow UK

8 London Research Institute (LRI) Erik Sahai UK

9 Universität Duisburg-Essen (UDE) Matthias Gunzer DE

10 SME 1 – Idea Biomedical (IB) Shlomo Turgeman IL

11 SME 2 – MetaViLabs (MVL) David Drell DE

capture, dissemination and analysis of multiscale cell

migration data for biological and clinical applications

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The Cell Migration Standardization Organization needs you!

www.cmso.science

CMSO@MULTIMOT

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A checklist trial on Minimum Information About a Cell Migration Experiment (MIACME)

• read a cell migration article (materials & methods)

• fill in the form reporting relevant information

• give a score to each unit of information

https://goo.gl/6Yn2xf

Image credits: Dr. AinePrendergast, Systems Biology

Ireland, Remedi, NUIG

https://goo.gl/6Yn2xf

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MULTIMOT will release key solutions forcell migration ecosystem to take place

Community standards for cell migration data

Open software to interact with the standards

Public cell migration data repository

Multiscale, meta-scale analysis algorithms

Applicability in defined model systems and personalised healthcare

Dissemination and durability

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modified from http://www.nps.gov/crmo/learn/education/activity-5a.htm

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www.multimot.orgwww.cmso.science

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Health & Medicine

MULTIMOT