A three-groups model for high-throughput survival screens

Benjamin Adam Shaby, Gaia Skibinski, Michael Ando, Eva S. LaDow, Steven Finkbeiner

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive deterioration of motor neurons in the cortex and spinal cord. Using an automated robotic microscope platform that enables the longitudinal tracking of thousands of single neurons, we examine the effects a large library of compounds on modulating the survival of primary neurons expressing a mutation known to cause ALS. The goal of our analysis is to identify the few potentially beneficial compounds among the many assayed, the vast majority of which do not extend neuronal survival. This resembles the large-scale simultaneous inference scenario familiar from microarray analysis, but transferred to the survival analysis setting due to the novel experimental setup. We apply a three-component mixture model to censored survival times of thousands of individual neurons subjected to hundreds of different compounds. The shrinkage induced by our model significantly improves performance in simulations relative to performing treatment-wise survival analysis and subsequent multiple testing adjustment. Our analysis identified compounds that provide insight into potential novel therapeutic strategies for ALS.

Original languageEnglish (US)
Pages (from-to)936-944
Number of pages9
JournalBiometrics
Volume72
Issue number3
DOIs
StatePublished - Sep 1 2016

Fingerprint

Amyotrophic Lateral Sclerosis
High Throughput
Neurons
Neuron
neurons
Throughput
Survival Analysis
Lateral
Simultaneous Inference
Robotics
Motor Neurons
Microarray Analysis
motor neurons
shrinkage
spinal cord
microscopes
Multiple Testing
Survival Time
Spinal Cord
cortex

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Cite this

Shaby, B. A., Skibinski, G., Ando, M., LaDow, E. S., & Finkbeiner, S. (2016). A three-groups model for high-throughput survival screens. Biometrics, 72(3), 936-944. https://doi.org/10.1111/biom.12479
Shaby, Benjamin Adam ; Skibinski, Gaia ; Ando, Michael ; LaDow, Eva S. ; Finkbeiner, Steven. / A three-groups model for high-throughput survival screens. In: Biometrics. 2016 ; Vol. 72, No. 3. pp. 936-944.
@article{7ab026b8a63d439fa8a02f43b2ae8e32,
title = "A three-groups model for high-throughput survival screens",
abstract = "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive deterioration of motor neurons in the cortex and spinal cord. Using an automated robotic microscope platform that enables the longitudinal tracking of thousands of single neurons, we examine the effects a large library of compounds on modulating the survival of primary neurons expressing a mutation known to cause ALS. The goal of our analysis is to identify the few potentially beneficial compounds among the many assayed, the vast majority of which do not extend neuronal survival. This resembles the large-scale simultaneous inference scenario familiar from microarray analysis, but transferred to the survival analysis setting due to the novel experimental setup. We apply a three-component mixture model to censored survival times of thousands of individual neurons subjected to hundreds of different compounds. The shrinkage induced by our model significantly improves performance in simulations relative to performing treatment-wise survival analysis and subsequent multiple testing adjustment. Our analysis identified compounds that provide insight into potential novel therapeutic strategies for ALS.",
author = "Shaby, {Benjamin Adam} and Gaia Skibinski and Michael Ando and LaDow, {Eva S.} and Steven Finkbeiner",
year = "2016",
month = "9",
day = "1",
doi = "10.1111/biom.12479",
language = "English (US)",
volume = "72",
pages = "936--944",
journal = "Biometrics",
issn = "0006-341X",
publisher = "Wiley-Blackwell",
number = "3",

}

Shaby, BA, Skibinski, G, Ando, M, LaDow, ES & Finkbeiner, S 2016, 'A three-groups model for high-throughput survival screens', Biometrics, vol. 72, no. 3, pp. 936-944. https://doi.org/10.1111/biom.12479

A three-groups model for high-throughput survival screens. / Shaby, Benjamin Adam; Skibinski, Gaia; Ando, Michael; LaDow, Eva S.; Finkbeiner, Steven.

In: Biometrics, Vol. 72, No. 3, 01.09.2016, p. 936-944.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A three-groups model for high-throughput survival screens

AU - Shaby, Benjamin Adam

AU - Skibinski, Gaia

AU - Ando, Michael

AU - LaDow, Eva S.

AU - Finkbeiner, Steven

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive deterioration of motor neurons in the cortex and spinal cord. Using an automated robotic microscope platform that enables the longitudinal tracking of thousands of single neurons, we examine the effects a large library of compounds on modulating the survival of primary neurons expressing a mutation known to cause ALS. The goal of our analysis is to identify the few potentially beneficial compounds among the many assayed, the vast majority of which do not extend neuronal survival. This resembles the large-scale simultaneous inference scenario familiar from microarray analysis, but transferred to the survival analysis setting due to the novel experimental setup. We apply a three-component mixture model to censored survival times of thousands of individual neurons subjected to hundreds of different compounds. The shrinkage induced by our model significantly improves performance in simulations relative to performing treatment-wise survival analysis and subsequent multiple testing adjustment. Our analysis identified compounds that provide insight into potential novel therapeutic strategies for ALS.

AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive deterioration of motor neurons in the cortex and spinal cord. Using an automated robotic microscope platform that enables the longitudinal tracking of thousands of single neurons, we examine the effects a large library of compounds on modulating the survival of primary neurons expressing a mutation known to cause ALS. The goal of our analysis is to identify the few potentially beneficial compounds among the many assayed, the vast majority of which do not extend neuronal survival. This resembles the large-scale simultaneous inference scenario familiar from microarray analysis, but transferred to the survival analysis setting due to the novel experimental setup. We apply a three-component mixture model to censored survival times of thousands of individual neurons subjected to hundreds of different compounds. The shrinkage induced by our model significantly improves performance in simulations relative to performing treatment-wise survival analysis and subsequent multiple testing adjustment. Our analysis identified compounds that provide insight into potential novel therapeutic strategies for ALS.

UR - http://www.scopus.com/inward/record.url?scp=85028256538&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028256538&partnerID=8YFLogxK

U2 - 10.1111/biom.12479

DO - 10.1111/biom.12479

M3 - Article

VL - 72

SP - 936

EP - 944

JO - Biometrics

JF - Biometrics

SN - 0006-341X

IS - 3

ER -

Shaby BA, Skibinski G, Ando M, LaDow ES, Finkbeiner S. A three-groups model for high-throughput survival screens. Biometrics. 2016 Sep 1;72(3):936-944. https://doi.org/10.1111/biom.12479