Preliminary data analysis

Patterns in data

Each example pairs one Oligoscan report with one Theriome Aristotle Plus report. Sixteen Theriome reports were supplied as PDFs. Example 4 was an early vendor-supplied CSV. The prepared data contain 42 direct Oligoscan rows and 296 direct Theriome analyte rows per example: 5,746 direct observations in total, with three unavailable numerical scores. A further 393 inferred cofactor scores are available separately.

NAD reference profiles - in all sixteen PDF reports, NADP is closer to its reference centre than NAD, while NADPH is further below its reference centre. This pattern recurs across the sixteen sets of source scores.

Example 4 - reported use of sublingual NAD+ and NAG adds potential confounding to its NAD and sugar-metabolite profile. Its CSV scoring method also differs from the PDF reports. These factors limit interpretation of its contrast with the other examples. A replacement PDF from the same original specimen has been requested to clarify the reporting-format difference. Supplement exposure remains relevant to interpretation.

The direct-marker comparison uses reported analyte rows. The tools’ inferred NAD, NADP, NADPH and ATP deficiency scores are available separately in the explorer. These derived scores depend on the observations used to calculate them.

For more on the potential causes and impact of these patterns, see remineralisation and toxic metals.

Other recurring marker patterns

The following comparisons use direct analyte rows from the sixteen Theriome PDF reports. Here, low flags combine LOW and IR-LOW; high flags combine HIGH and IR-HIGH. These are the tool’s classifications. An unflagged result retains its reported score and has no source status flag.

Biotin - carries an IR-LOW flag in all sixteen PDF reports, with z-scores ranging from -0.81 to -0.53.

5-Hydroxytryptophan - carries an IR-LOW flag in all sixteen PDF reports, with z-scores ranging from -0.74 to -0.59.

Fructose - thirteen of sixteen PDF reports carry a high flag. Examples 12, 13 and 17 are unflagged. Fourteen of sixteen scores are above the reference centre; Examples 12 and 13 are slightly below it.

Fructose 1,6-bisphosphate - fifteen of sixteen PDF reports carry a low flag. Example 7 is unflagged, with a z-score of +0.40. High fructose and low fructose 1,6-bisphosphate occur together in twelve of sixteen reports.

N-Acetyl-D-galactosamine - all sixteen PDF scores are below the reference centre, with low flags in fifteen reports. Example 14 is unflagged, with a z-score of -0.49.

Uridine diphosphate-N-acetylglucosamine - all sixteen PDF scores are below the reference centre, with low flags in fourteen reports. Examples 12 and 17 are unflagged, at -0.46 and -0.45 z respectively. This marker and N-acetyl-D-galactosamine both carry low flags in thirteen of sixteen reports.

Mannose 6-phosphate - eleven of sixteen PDF reports carry high flags. Examples 6 and 16 carry low flags; Examples 8, 12 and 14 are unflagged. The predominant direction is upward, with variation between examples.

Glutamic acid - eleven of sixteen PDF reports carry high flags. The other five, Examples 1, 3, 9, 12 and 14, carry low flags.

Gamma-aminobutyric acid (GABA) - all sixteen PDF scores are below the reference centre, ranging from -0.81 to -0.19 z. Thirteen reports carry an IR-LOW flag; Examples 11, 12 and 15 are unflagged. High glutamic acid and low GABA flags occur together in nine of sixteen reports.

Betaine and methionine - both carry an IR-LOW flag in all sixteen PDF reports. Betaine z-scores range from -0.81 to -0.64; methionine ranges from -0.75 to -0.54.

Creatine - all sixteen PDF scores are below the reference centre, ranging from -0.77 to -0.15 z, with a median of -0.60. Eleven reports carry an IR-LOW flag; Examples 6, 8, 11, 14 and 17 are unflagged.

Phosphocreatine - all sixteen PDF scores are below the reference centre, ranging from -0.67 to -0.49 z. Fifteen reports carry an IR-LOW flag; Example 13 is unflagged at -0.49 z. Creatine and phosphocreatine show a shared downward pattern. Establishing impaired synthesis requires additional evidence.

Example 4’s CSV also flags biotin and 5-hydroxytryptophan low. It flags glutamic acid high and GABA, betaine and methionine low. Creatine is flagged HIGH at +543.1% on its CSV reference-based scale; phosphocreatine is IR-LOW at -69.6%. Its low fructose and high N-acetyl-D-galactosamine contrast with the predominant PDF directions. Its different scoring method and reported supplement exposure need to be considered together.

Urea-cycle-related markers

Arginine, citrulline, ornithine, aspartate and fumarate participate in the urea cycle. Their direct scores in the sixteen PDF reports show the following patterns.

Arginine and citrulline - each carries low flags in nine of sixteen PDF reports. Arginine scores are below the reference centre in fifteen reports; Example 15 is HIGH at +1.40 z, and six reports are unflagged. Citrulline scores are below the reference centre in fourteen reports; Example 14 is IR-HIGH at +0.77 z, and six reports are unflagged, including Example 6 at +0.20 z.

Ornithine and aspartate - each carries an IR-LOW flag in eight of sixteen PDF reports. Ornithine has eight unflagged results, with no high flags; ten scores are below the reference centre, five above it and one at zero. Aspartate has twelve scores below the reference centre, seven unflagged results and an IR-HIGH flag in Example 16 at +0.89 z.

Fumaric acid - thirteen PDF reports are unflagged. Examples 6 and 16 carry IR-HIGH flags and Example 7 is HIGH. Ten scores are below the reference centre, with no low flags.

Example 4’s CSV flags arginine, citrulline, ornithine and aspartate low; fumaric acid is unflagged. Urea, ammonia and argininosuccinate are absent from the prepared dataset. Assessing urea-cycle flux or ammonia clearance requires additional measurements and clinical context.

Explore the paired data

Select an example to follow its NAD pathway profile, inspect individual markers and their peaks or troughs, or compare grouped heatmaps. Marker summaries are calculated within their source scoring group, with separate summaries for CSV and PDF direct scores.

NADP formation and redox handling

NAD kinase phosphorylates NAD+ to NADP+ using ATP. Magnesium-dependent activity has been demonstrated in human NAD kinase preparations. A distinct mitochondrial NAD kinase also exists. These findings provide a biochemical basis for examining magnesium, ATP, NAD and NADP together. Williams and Jones, 1985; Ohashi and colleagues, 2012.

Two questions guide this comparison: whether the marker pattern is compatible with constraints on NADP formation, and whether NADP/NADPH findings are compatible with altered reduction or consumption. Both require several markers and relevant clinical context. NADPH metabolism is compartmentalised; resolving cytosolic and mitochondrial processes requires compartment-specific methods. Lewis and colleagues, 2014.

Example 7 combines high ATP with low Oligoscan magnesium. Example 8 combines IR-LOW ATP with a NADP score of -0.11 z. These combinations help assess how well a proposed explanation accommodates variation across the examples.

Estimating NADPH:NADP concentration ratios, total NADP/NADPH pool size or NAD kinase activity requires suitable measurements, units and assay calibration. These inputs are unavailable in the prepared data.

Silicon and aluminium

Low silicon and elevated aluminium co-occur across all seventeen Oligoscan reports. The inverse rank association describes variation within this selected set of tool scores. Exposure history, diet, assay behaviour and other shared influences could contribute to it.

Silica chemistry provides a reason to examine these markers together. In a tracer study of three healthy volunteers, oligomeric silica reduced gastrointestinal aluminium uptake. The monomeric form showed no significant effect under the study conditions. Jugdaohsingh and colleagues, 2000.

Those findings concern chemical form and gut absorption. Applying this mechanism to the report pattern requires information about exposure, silicon form and independent measurements of aluminium handling. Both scores here come from the same Oligoscan report, so their association also requires validation with independent measurements.

Common patterns described in MPO

The following proposed patterns and mechanisms form the working interpretation framework for the Metabolic Pathway Overlay examples. Each requires assessment against the individual reports and supporting evidence. Mechanism-specific scoring is a future analysis step.

1. Elevated toxic metals, with mineral and electrolyte deficiencies.
2. A reduced total NADP/NADPH pool and impaired conversion of NADP to NADPH (low NADPH), with potentially broad effects. The reported exception is where aluminium is not elevated.
3. Constraints on glycolysis and glycogen synthesis.
4. Altered pyruvate and/or lactate levels.
5. Constraints on the pentose phosphate pathway and downstream PRPP synthesis.
6. Impairments in purine and pyrimidine metabolism.
7. Oxidative stress.
8. TCA cycle alterations and constraints.
9. Issues with NAD+ synthesis and redox balance.
10. Reduced carnitine synthesis and associated carnitine-shuttle constraints.
11. Elevated glutamate relative to low GABA, except where severe malnutrition constrains glutamate synthesis.
12. Issues with glutathione metabolism.
13. Issues involving magnesium and Mg-ATP.
14. Urea-cycle and nitric oxide synthase impairments, with potential effects on vascular tone.
15. Dysregulated neurotransmitter synthesis and degradation.
16. Impaired conversion of choline to betaine.
17. Impaired methylation and associated SAMe, glycine, and cysteine metabolism.
18. Impaired creatine synthesis.

Testing the exception in pattern 2 requires a comparison group with non-elevated aluminium; all seventeen examples here have elevated aluminium scores. Assessing the malnutrition exception in pattern 11 requires clinical nutritional information, which is unavailable. The proposed changes in pool size, pathway flux and enzyme activity also require further investigation.

How to read the scores

Theriome PDFs - the displayed score is the source z-score multiplied by 100, consistent with MPO’s numerical convention. For example, -168 means z = -1.68, or 1.68 standard deviations below the reference centre. This explorer has its own labelled heatmap colour scale.

Example 4 CSV - the original tool-derived relative-abundance/reference score is retained and summarised separately from the PDF scores.

Oligoscan - mineral deviation scores, vitamin percentages and metal scores retain their source meanings. Each scale requires its own interpretation.

Inferred cofactors - rules applied to report observations generate these visual scores. Their clinical significance requires independent validation. Missing inferred rows remain unreported.

Missing data - unavailable scores appear as NA. Blank source status flags remain blank. Both retain an unspecified status in the comparison.

Limits of this comparison

The dataset contains seventeen selected pairs and lacks a healthy control group. Its population relevance is unknown. Collection dates, the interval between paired tests, specimen details, units and most clinical context are unavailable in the prepared data. Example 4 has reported exposure to sublingual NAD+ and NAG; doses and timing are not recorded here. Supplement use in the other examples is unspecified. Tissue and biochemical compartment differences remain unresolved.

Examples 1-10 retain their original prepared results. Examples 11-17 were processed with newer parser versions: Oligoscan 1.6.9 and Universal OAT 0.1.43, compared with 1.6.6 and 0.1.40 for the original batch. Parser versions are retained in the downloads; rule-derived comparisons may be affected by changes between versions.

There are many markers relative to the number of examples. Apparent correlations may be sensitive to individual cases, scoring conventions, selection and shared reference distributions. Analysis is limited to descriptive summaries. A direct-row label records the parser’s classification; assay validity requires separate evaluation.

Pending

Resolve Example 4 - compare the replacement PDF with the retained vendor CSV from the same specimen, and review the timing and doses of the reported NAD+ and NAG use when interpreting its profile.

Describe marker coherence - compare direction, magnitude and variability within compatible scoring groups, retaining all exceptions and denominators.

Mechanism map and references - MPO already provides much of the mechanism mapping. A supporting table of references is in progress.

Assess concordance - show supporting observations, contradictions and missing evidence. Report mechanistic evidence, measurement relevance, coverage and sensitivity to individual examples separately.

The downloadable CSV and JSON contain the prepared de-identified observations, source scores and marker identities for future analyses.