MultiplexMS: A mass spectrometry-based multiplexing strategy for ultra-high-throughput analysis of complex mixtures
Bibliographic record
Abstract
Abstract: Throughput for chemical analysis of natural products mixtures has not kept pace with recent developments in genome sequencing technologies and laboratory automation for high-throughput screening, leading to a disconnect between chemical and biological profiling at the library scale that limits new molecule discovery. Here we report a new strategy for sample multiplexing that can increase mass spectrometry-based profiling up to 30-fold over traditional methods. This strategy involves the analysis of pooled samples and subsequent computational deconvolution to reconstruct peak lists for each sample in the set. We validated this approach using in silico experiments and demonstrated that the method has a high precision (>97%) for large, pooled samples (n = 30), particularly for infrequently occurring metabolites (n < 10) of relevance in drug discovery applications. Finally, we repeated a recently reported biological activity profiling study on 925 natural products extracts, leading to the rediscovery of all previously reported bioactive metabolites using just 5% of the previously required MS acquisition time. This new method is compatible with mass spectrometry data from any instrument vendor and is supported by an open-source software package available at https://github.com/liningtonlab/MultiplexMS.Throughput for chemical analysis of natural products mixtures has not kept pace with recent developments in genome sequencing technologies and laboratory automation for high-throughput screening, leading to a disconnect between chemical and biological profiling at the library scale that limits new molecule discovery. Here we report a new strategy for sample multiplexing that can increase mass spectrometry-based profiling up to 30-fold over traditional methods. This strategy involves the analysis of pooled samples and subsequent computational deconvolution to reconstruct peak lists for each sample in the set. We validated this approach using in silico experiments and demonstrated that the method has a high precision (>97%) for large, pooled samples (n = 30), particularly for infrequently occurring metabolites (n < 10) of relevance in drug discovery applications. Finally, we repeated a recently reported biological activity profiling study on 925 natural products extracts, leading to the rediscovery of all previously reported bioactive metabolites using just 5% of the previously required MS acquisition time. This new method is compatible with mass spectrometry data from any instrument vendor and is supported by an open-source software package available at https://github.com/liningtonlab/MultiplexMS.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".