Omics, Analysis, and Data Infrastructure

Omics, Analysis, and Data Infrastructure

Systems-level measurement, standardized — anchored by genomics and ALEdb

Systems-level measurement, standardized — anchored by genomics and ALEdb

A single measurement rarely explains a phenotype. When a strain behaves differently, the cause may sit in its genome, in how much of a given protein it makes, in what it secretes, or in the rate at which it consumes a substrate. So we strive to measure all of it, on the same strains and under the same conditions. That is our definition of systems biology. Genome resequencing forms the core: standardized workflows take raw reads to annotated variants, with automated detection of point mutations, insertions and deletions, mobile-element movements, and larger structural rearrangements, covering the full range of changes a genome actually undergoes rather than just the ones easiest to call. Around that core we run transcriptomics, proteomics, and exometabolomics at experiment scale, together with quantitative phenomic measurements of growth, uptake, and secretion. Because these workflows are standardized rather than assembled per project, a measurement made in one experiment means the same thing as the equivalent measurement made three years earlier in a different organism, which is the precondition for comparing anything at all.

Comparability only becomes useful once the data is structured, which is what ALEdb provides. Our contribution to the field's data infrastructure, ALEdb is an open, queryable database holding evolution experiments together with their genetic changes, the conditions that produced them, and the phenotypes that resulted, with each measurement linked to its experimental context rather than deposited as an isolated file. That structure is what makes system-wide questions answerable: the same mutation can be traced across studies, conditions, and organisms, and expression or metabolite changes can be examined for the conditions that reliably provoke them. It also makes the accumulated record directly usable by statistical, machine learning, and AI methods, which require exactly this kind of labeled, standardized input and rarely have access to it in biology. We release data in FAIR-compliant form so that others can use it the way we do: reusable, not merely publishable, though we recommend that as well.

ALE-evolved chemical tolerance is structurally specific: gains extend to similar compounds but can come with tradeoffs on dissimilar ones. Cross-compound phenotyping of 192 E. coli isolates evolved against 11 industrial chemicals shows that tolerization to a given compound generally improves performance on structurally related molecules, while correlation with NaCl tolerance identifies osmotic stress as a mechanistic thread running across many of the conditions. Lennen and Lim et al., Metab Eng 76:179–192, 2023.

ALE-evolved chemical tolerance is structurally specific: gains extend to similar compounds but can come with tradeoffs on dissimilar ones. Cross-compound phenotyping of 192 E. coli isolates evolved against 11 industrial chemicals shows that tolerization to a given compound generally improves performance on structurally related molecules, while correlation with NaCl tolerance identifies osmotic stress as a mechanistic thread running across many of the conditions. Lennen and Lim et al., Metab Eng 76:179–192, 2023.

Pleiotropic RNA polymerase mutations globally rebalance cellular resources between growth and stress-hedging. Three E. coli rpoB/rpoC point mutations selected by ALE consistently upregulate protein synthesis, transport, and metabolic functions while broadly suppressing osmotic, oxidative, and other stress-response programs — demonstrating how a single adaptive mutation can reprogram the entire transcriptional hierarchy to favor growth in stable conditions. Utrilla et al., Cell Syst 2:260–271, 2016.

Pleiotropic RNA polymerase mutations globally rebalance cellular resources between growth and stress-hedging. Three E. coli rpoB/rpoC point mutations selected by ALE consistently upregulate protein synthesis, transport, and metabolic functions while broadly suppressing osmotic, oxidative, and other stress-response programs — demonstrating how a single adaptive mutation can reprogram the entire transcriptional hierarchy to favor growth in stable conditions. Utrilla et al., Cell Syst 2:260–271, 2016.

Large-scale TALE experiments in Pseudomonas putida reveal both condition-specific and broadly shared genomic targets for tolerance to lignin-derived aromatic acids. Whole-genome sequencing across populations evolved on p-coumaric acid (pCA), ferulic acid (FA), and their combination identifies overlapping and distinct mutation hotspots with the degree and combination of stress selecting for either specialized or generalist adaptive solutions. Mohamed et al., Metab Eng Commun 11:e00143, 2020.

Large-scale TALE experiments in Pseudomonas putida reveal both condition-specific and broadly shared genomic targets for tolerance to lignin-derived aromatic acids. Whole-genome sequencing across populations evolved on p-coumaric acid (pCA), ferulic acid (FA), and their combination identifies overlapping and distinct mutation hotspots with the degree and combination of stress selecting for either specialized or generalist adaptive solutions. Mohamed et al., Metab Eng Commun 11:e00143, 2020.

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San Diego, CA

University of California San Diego

Copenhagen, Denmark

Technical University of Denmark

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In accordance with applicable Federal and State law and University policy, the University of California does not discriminate, or grant preferences, on the basis of race, color, national origin, religion, sex, disability, and/or other protected categories. More information about Proposition 209 can be found here. More information about the University of California Anti-Discrimination Policy can be found here. Initiatives are open to all eligible members of the UC San Diego campus community and does not discriminate against, or grant preferential treatment to, any individual or group on the basis of race, color, national origin, religion, sex, disability, and/or other protected categories.

©2026 by Adam Feist and UC San Diego. All rights reserved.

Lab Locations

San Diego, CA

University of California San Diego

Copenhagen, Denmark

Technical University of Denmark

Get in Touch

Follow Us

In accordance with applicable Federal and State law and University policy, the University of California does not discriminate, or grant preferences, on the basis of race, color, national origin, religion, sex, disability, and/or other protected categories. More information about Proposition 209 can be found here. More information about the University of California Anti-Discrimination Policy can be found here. Initiatives are open to all eligible members of the UC San Diego campus community and does not discriminate against, or grant preferential treatment to, any individual or group on the basis of race, color, national origin, religion, sex, disability, and/or other protected categories.


©2026 by Adam Feist and UC San Diego. All rights reserved.