Temporal gene-expression distribution prediction

T1 · Temporal — Given stages before a target time, predict the gene-expression distribution — a set of cells — at a future stage. Tests temporal extrapolation.

The question

Participants will predict the gene-expression distribution of a whole embryo at a developmental stage the model has never seen, given the stages before it. The prediction is a population of cells — progenitors, differentiating cells and terminal types in their real proportions — not an average cell. A model that collapses onto the mean profile forfeits most of the panel.

Staging an embryo is destructive and each time point is a different animal, so a stage that was not collected cannot be recovered by re-running the experiment; and the gap between collected stages is often where the interesting transitions happen. Here nothing sits between the validation and test stages at all, so interpolation has nothing to lean on.

To keep the task tractable we release two fully observed earlier stages of real dissociated single cells — RNA across the whole transcriptome, not the 500-gene MERFISH panel Tasks 2 and 3 use. Participants may additionally train on external public single-cell data; only the evaluation stages are fixed, and any external source must be disclosed with the submission.

Three populations of dissociated cells side by side, each a swarm of separate cells inside a density boundary. The E8.5 and E9.5 swarms are filled; the E12.5 boundary is drawn in violet and is empty.
Three different embryos, not one embryo followed over time — profiling destroys the embryo, so there is no cell-level correspondence between stages. What is predicted is the distribution at E12.5, and no morphology is involved.

Modality

Real dissociated single cells. Whole transcriptome — 32,285 genes, log1p-normalised, with cell-type annotation — and explicitly not the 500-gene MERFISH panel that Tasks 2 and 3 use. There are no spatial coordinates in this modality, and none are expected in a Task 1 submission.

Splits

Validation and test ground truth are both withheld. A validation submission returns a leaderboard score, not the answers — those are released only when the final test set is.

Train
E8.5 · E9.5
The two real single-cell stages before the target. There is no E9.25 in this release.
Validation
E10.5
Scored through the leaderboard; the answers are not distributed.
Test
E12.5
Hidden. Scored only in the final phase.
Outside the split
E7.75
Ships with the release, usable as background, not part of the split.

Input and output

Input
The public training stages, as per-cell expression matrices with cell-type annotation. Participants may additionally train on external public single-cell data — only the evaluation stages are fixed — provided the source is disclosed with the submission. At inference the model is given the target stage and must emit a predicted set of cells for it.
Output
An AnnData file whose .X is the predicted expression matrix on the task gene panel, in panel order. No cell-type labels: the organisers assign types with a frozen classifier applied identically to every submission.

The exact file contract and validation rules →

How it is scored

Four metrics rank Task 1, each its own weighted question: DE gene recovery 25%, change direction 25%, cell-state distribution 30%, gene-gene co-variation 20%. Task 1 has no spatial component, so no shape term applies.

25%
DE gene recovery

Did you get the key up- and down-genes right?

25%
Change direction

Genome-wide direction and ranking of the change.

30%
Cell-state distribution

The right cell states, in the right proportions.

20%
Gene-gene co-variation

Co-regulation preserved, not just per-gene marginals.

Every metric, with its derivation →

What the starter kit ships

Transparent reference points, not competitive upper bounds — a floor, a simple method, and a dynamics reference model, all with the exact evaluation code.

  • copy_last — the floor.
  • pseudobulk_shift — a one-line constant shift by the observed pseudobulk delta.
  • shift_ode — kept because its minimiser is that same constant shift, so the equivalence stays visible.
  • neural_ode — an autonomous field in gene space, flow-matched on a global entropic-OT coupling.
  • dynode_flow — the external flow-matching reference model, unmodified.

Why it’s hard

  • No observed stage sits between E10.5 and E12.5, so naive temporal interpolation has nothing to lean on.
  • E8.5 and E9.5 share only 5 cell types out of 33 and 22 — roughly a third of target cells have a same-type predecessor at all. The rest did not drift into place, they differentiated, so velocity extrapolation is the wrong frame for most of the target.
  • The reference neural ODE does not beat the one-line constant shift, and that is the published result rather than a bug. Clearing the floor plausibly needs supervision across the whole stage ladder, a non-autonomous field, and a treatment of populations appearing rather than only existing ones moving.
  • The floor is not weak: fitting the same extrapolation off the evaluation stages lands every setting below copy_last, the constant shift included.

Common pitfalls

  • Predicting a tightly clustered distribution — mode collapse clears a mean-based diagnostic and then fails ED, MMD and CSS.
  • Submitting a scaled copy of the reference. Both DE metrics now measure a null built from exactly that attack, in both directions.
  • Assuming the panel is the 500-gene MERFISH set. Task 1 is whole-transcriptome single-cell.
  • Including cell-type labels and tuning to them — labels are never part of a submission and are re-assigned by the frozen probe.

Other tasks

The task documents, exact metric implementations and executed tutorials live in the baselines repo ↗; where this page and the repo differ, the repo is authoritative. Otherwise reach the organisers at [email protected].