Nonlinear mixed-effects modelling for single cell estimation: when, why, and how to use it

BMC Systems Biology
Markus KarlssonGunnar Cedersund

Abstract

Studies of cell-to-cell variation have in recent years grown in interest, due to improved bioanalytical techniques which facilitates determination of small changes with high uncertainty. Like much high-quality data, single-cell data is best analysed using a systems biology approach. The most common systems biology approach to single-cell data is the standard two-stage (STS) approach. In STS, data from each cell is analysed in a separate sub-problem, meaning that only data from the same cell is used to calculate the parameter values within that cell. Because only parts of the data are considered, problems with parameter unidentifiability are exaggerated in STS. In contrast, a related approach to data analysis has been developed for the studies of patient-to-patient variations. This approach, called nonlinear mixed-effects modelling (NLME), makes use of all data, when estimating the patient-specific parameters. NLME would therefore be advantageous compared to STS also for the study of cell-to-cell variation. However, no such systematic evaluation of the two approaches exists. Herein, such a systematic comparison between STS and NLME has been performed. Different examples, both linear and nonlinear, and both simulated and real exp...Continue Reading

References

Oct 2, 1998·Pharmaceutical Research·E N Jonsson, M O Karlsson
Dec 14, 2001·AAPS PharmSci·E N JonssonM O Karlsson
Jun 24, 2004·Computer Methods and Programs in Biomedicine·Lars LindbomE Niclas Jonsson
Jul 19, 2005·Computer Methods and Programs in Biomedicine·Lars LindbomNiclas Jonsson
Sep 20, 2005·Nature·Alejandro Colman-LernerRoger Brent
Oct 10, 2006·Annals of Biomedical Engineering·Min SuHiroki Yokota
May 29, 2007·FEBS Letters·Hyung-Seok ChoiKwang-Hyun Cho
Aug 30, 2008·Nature·Nicholas T Ingolia, Jonathan S Weissman
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Loïc de PontualJeanne Amiel
Dec 3, 2009·Genes & Development·Ralph A Neumüller, Juergen A Knoblich
Jun 29, 2011·The FEBS Journal·Katrin HübnerUrsula Kummer
May 9, 2012·Proceedings of the National Academy of Sciences of the United States of America·Christoph ZechnerHeinz Koeppl
Jan 15, 2014·Nature Methods·Christoph ZechnerHeinz Koeppl
Jan 15, 2015·The FEBS Journal·Elin NymanGunnar Cedersund

❮ Previous
Next ❯

Citations

Jun 7, 2017·BMC Systems Biology·Niek WelkenhuysenStefan Hohmann
Dec 20, 2018·NPJ Systems Biology and Applications·Fabian FröhlichJan Hasenauer
Sep 15, 2020·Frontiers in Physiology·Sebastian PerssonMarija Cvijovic
Dec 4, 2020·Journal of Theoretical Biology·Ben LambertSimon J Tavener

❮ Previous
Next ❯

Software Mentioned

SPBDsimulate
MATLAB
Systems Biology Toolbox2 ( SBTB2 )
JLH
NONMEM
ImageJ
TRAN
speaks
lsqnonlin
STS

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.