Reproducing legacy results

HumanBase, like all resources that use external databases, must manage the incorporation of new versions of annotations from those databases. HumanBase is in the process of updating our process for managing versions, how it changes query results, and user’s access to reproducing prior results. The current versions of HumanBase’s gene records and annotation sources are listed on the Data sources page, under the Resources menu in the site header.

Annotation source drift

HumanBase imports gene records and term annotations from external sources (NCBI, Gene Ontology, MSigDB, MeSH, and others) on its own schedule. As an example of how drift can affect reproducibility, in networks the GO term enrichment hypergeometric calculation uses two quantities that can drift between versions:

  • the gene universe (M) — the set of distinct genes with at least one annotation, summed across the loaded organisms; and

  • each term size (K) — the number of distinct genes annotated to a given term.

In practice this means a Functional Module Detection run with different database versions will reproduce the exact statistical calculation used in the legacy code path, but the inputs M and K reflect the annotation tables currently used by HumanBase, not the tables present at the time of a query using a different database version. Q values shift in proportion to how much the underlying knowledge base has drifted since.

Network Enrichment before June 2026

GO term enrichment in Functional Module Detection and tissue-specific GIANT networks use annotations from UniProt-GOA (experimental evidence codes). Between February 2024 and May 2026 cross-organism annotations were included; outside of this window human-only annotations are used.

The effect of including cross-organism annotations was a slight inflation of q-values and enriched terms comparable to when human-only annotations were used. You can reproduce results by either:

  1. modifying the URL for your original query as directed below, or

  2. reproducing the query with the gene list and GIANT network and then modifying the URL.

How to reproduce network GO enrichment values from Feb 2024 – May 2026

Append extended_universe=true to the URL of a community page or gene page. For example:

  • Functional module detection result:

    https://humanbase.io/module/overview/?body_tag=<job_id>&extended_universe=true

  • Gene page:

    https://humanbase.io/gene/3553/blood?extended_universe=true

Programmatic access

The same parameter is forwarded to the underlying API endpoints (/community/ and /terms/annotated/). Scripts replaying historical analyses through the API should append &extended_universe=true to the query string.

Details of changes

Adding extended_universe=true reproduces HumanBase’s exact output for any GIANT Functional Module Detection result generated between February 2024 and May 2026. The flag restores both the cross-organism annotation universe and the point-probability calculation that the platform used at the time.

Term enrichment in Functional Module Detection uses a one-sided Fisher’s exact test followed by Benjamini–Hochberg correction. Two inputs to that test depend on which annotation universe is in effect:

  • Term size (K). The number of genes annotated to the term.

  • Background universe (N). The total number of genes considered available for annotation.

In the current default mode, both K and N are computed from human annotations only. In extended-universe mode, K and N include annotations from non-human organisms that were carried over from the source databases: mouse (Mus musculus), zebrafish (Danio rerio), fruit fly (Drosophila melanogaster), nematode worm (Caenorhabditis elegans), and budding yeast (Saccharomyces cerevisiae).

Where the extended_universe flag applies

The flag is supported only for GIANT networks (the original human tissue and biological-process networks). MAGE network analyses have used a human-only annotation pipeline from the start, so there is no legacy cross-organism behavior to reproduce. Requests that combine extended_universe=true with a MAGE network are rejected by the API.

The flag applies to the GIANT version of:

It does not affect network edge weights, gene-prediction scores, or any non-enrichment output.