PMID- 33638725 OWN - NLM STAT- MEDLINE DCOM- 20211206 LR - 20211214 IS - 1615-7605 (Electronic) IS - 1615-7591 (Print) IS - 1615-7591 (Linking) VI - 44 IP - 6 DP - 2021 Jun TI - Design of experiment (DOE) applied to artificial neural network architecture enables rapid bioprocess improvement. PG - 1301-1308 LID - 10.1007/s00449-021-02529-3 [doi] AB - Modern bioprocess development employs statistically optimized design of experiments (DOE) and regression modeling to find optimal bioprocess set points. Using modeling software, such as JMP Pro, it is possible to leverage artificial neural networks (ANNs) to improve model accuracy beyond the capabilities of regression models. Herein, we bridge the gap between a DOE skill set and a machine learning skill set by demonstrating a novel use of DOE to systematically create and evaluate ANN architecture using JMP Pro software. Additionally, we run a mammalian cell culture process at historical, one factor at a time, standard least squares regression, and ANN-derived set points. This case study demonstrates the significant differences between one factor at a time bioprocess development, DOE bioprocess development and the relative power of linear regression versus an ANN-DOE hybrid modeling approach. FAU - Rodriguez-Granrose, Daniel AU - Rodriguez-Granrose D AD - DiscGenics Inc, Salt Lake City, Utah, USA. daniel@discgenics.com. AD - Department of Biochemistry and Molecular Biology, University of Miami, Miami, FL, USA. daniel@discgenics.com. FAU - Jones, Amanda AU - Jones A AD - DiscGenics Inc, Salt Lake City, Utah, USA. FAU - Loftus, Hannah AU - Loftus H AD - DiscGenics Inc, Salt Lake City, Utah, USA. FAU - Tandeski, Terry AU - Tandeski T AD - DiscGenics Inc, Salt Lake City, Utah, USA. FAU - Heaton, Will AU - Heaton W AD - DiscGenics Inc, Salt Lake City, Utah, USA. FAU - Foley, Kevin T AU - Foley KT AD - DiscGenics Inc, Salt Lake City, Utah, USA. AD - Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN, USA. AD - Semmes-Murphey Clinic, Memphis, TN, USA. FAU - Silverman, Lara AU - Silverman L AD - DiscGenics Inc, Salt Lake City, Utah, USA. AD - Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN, USA. LA - eng GR - 1451511/National Science Foundation Graduate Research Fellowship/ PT - Journal Article DEP - 20210227 PL - Germany TA - Bioprocess Biosyst Eng JT - Bioprocess and biosystems engineering JID - 101088505 SB - IM MH - *Models, Biological MH - *Neural Networks, Computer MH - *Software PMC - PMC8144078 OTO - NOTNLM OT - Artificial neural network OT - Bioprocess OT - Design of experiments (DOE) OT - MachineLearning OT - Process modeling COIS- D Rodriguez-Granrose, H Loftus, A Jones, T Tandeski, W Heaton, K Foley and L Silverman are employees at DiscGenics. D Rodriguez-Granrose, H Loftus, A Jones, T Tandeski, W Heaton, K Foley and L Silverman own stock or stock options in DiscGenics. K Foley is on the board of DiscGenics. EDAT- 2021/02/28 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/02/27 CRDT- 2021/02/27 12:07 PHST- 2020/09/11 00:00 [received] PHST- 2021/02/04 00:00 [accepted] PHST- 2021/02/28 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/02/27 12:07 [entrez] PHST- 2021/02/27 00:00 [pmc-release] AID - 10.1007/s00449-021-02529-3 [pii] AID - 2529 [pii] AID - 10.1007/s00449-021-02529-3 [doi] PST - ppublish SO - Bioprocess Biosyst Eng. 2021 Jun;44(6):1301-1308. doi: 10.1007/s00449-021-02529-3. Epub 2021 Feb 27.