---
tags:
- chemistry
- biology
pretty_name: A-Alpha Bio open source data
size_categories:
- 10K<n<10M
configs:
  - config_name: YM_0005
    data_files:
      - split: all
        path: "data/YM_0005/data.parquet"
  - config_name: YM_0549
    data_files:
      - split: all
        path: "data/YM_0549/data.parquet"
  - config_name: YM_0693
    data_files:
      - split: all
        path: "data/YM_0693/data.parquet"
  - config_name: YM_0852
    data_files:
      - split: all
        path: "data/YM_0852/data.parquet"
  - config_name: YM_0985
    data_files:
      - split: all
        path: "data/YM_0985/data.parquet"
  - config_name: YM_0988
    data_files:
      - split: all
        path: "data/YM_0988/data.parquet"
  - config_name: YM_0989
    data_files:
      - split: all
        path: "data/YM_0989/data.parquet"
  - config_name: YM_0990
    data_files:
      - split: all
        path: "data/YM_0990/data.parquet"
  - config_name: YM_1068
    data_files:
      - split: all
        path: "data/YM_1068/data.parquet"
---
# A-Alpha Datasets

Protein-protein interactions (PPIs) are fundamental to countless biological processes. One of the most informative biophysical properties of a PPI is the binding affinity: the strength of how two proteins interact. Yet, despite its importance, publicly available affinity data remains limited, constaining the development and benchmarking of protein modeling methods.

Our high-throughput yeast mating assay, [AlphaSeq](https://www.pnas.org/doi/10.1073/pnas.1705867114), enables the quantitative measurement of PPIs at scale (often generating libraries up to 1M interactions per experiment!).

To help bridge the gap between experimental affinity measurements and computational protein models, we’re open-sourcing a selection of our datasets.

Each dataset captures the results of a yeast mating experiment between two protein libraries—one of binders and one of targets. Detailed experimental context and metadata are provided in the accompanying data cards.

## Dataset schema

| Column | Description |
|:--------|:-------------|
| **mata_description** | Unique description of each MATa library element. Also contains negative control strains (ANeg1, ANeg2, ANeg3). Often supplemented with assay-specific information such as nomenclature or replicate labeling. |
| **matalpha_description** | Unique description of each MATα library element. Also contains negative control strains (AlphaNeg1, AlphaNeg2, AlphaNeg3). Often supplemented with assay-specific information such as nomenclature or replicate labeling. |
| **mata_sequence** | Amino acid sequence corresponding to the MATa library element. The sequence excludes linkers, epitope tags, and the cell wall anchor Aga2, and is empty for negative controls. |
| **matalpha_sequence** | Amino acid sequence corresponding to the MATα library element. The sequence excludes linkers, epitope tags, and the cell wall anchor Aga2, and is empty for negative controls. |
| **alphaseq_affinity** | Pairwise interaction affinity, reported as log₁₀(estimated Kd in nM). Values map as –1 = 0.1 nM, 0 = 1 nM, 1 = 10 nM, 2 = 100 nM, etc. Missing values indicate no observed cell fusions between the protein pair (see Younger et al., 2017). |
| **affinity_upper_bound** | Upper (stronger) bound of the 95 % confidence interval for `alphaseq_affinity`, computed with the Wilson score interval. Provided even when no point estimate is available. |
| **affinity_lower_bound** | Lower (weaker) bound of the 95 % confidence interval for `alphaseq_affinity`, computed with the Wilson score interval. |
| **normalized_affinity** | Z-score comparing each interaction’s affinity to the distribution of all interactions involving the same MATa or MATα protein. Computed by successive normalization of the affinity matrix (Olshen & Rajaratnam 2010). More negative values indicate higher specificity (e.g., –2 ≈ 2 SD below the mean). Strongly negative values are not expected when many proteins bind broadly. |
| **above_background** | Boolean flag indicating whether the interaction affinity is significantly stronger than the assay background (q < 0.05, Benjamini–Hochberg corrected t-test). |
| **sufficient_replicate_observations** | Boolean flag indicating whether the interaction was observed in > 50 % of replicate samples. A value of False suggests a potentially spurious or unreliable interaction. |

## FAQ

Please see below for some clarifying details:

### Where can I find experimental details for each dataset?

Each dataset has a corresponding README.md in its subfolder summarizing the experiment's goals, library composition, and citation info. See `./data/YM_0005/README.md` for an example.

### What kind of sequences are in the library?

While not a strict rule, the A-libraries typically contain designed sequences, while the Alpha-libraries contain corresponding targets of interest. Historically, we’ve used VHHs or scFvs in the A-library and antigen targets in the Alpha-library. Each dataset will have a card that details specific information of the individual assay run. When building or training models, note that PPIs can generally be treated as symmetric. However, members within the same library may share sequence, functional, or structural similarities. Also, some models are sensitive to input order — so ensure that (A, Alpha) pairs are treated consistently between training and testing.

### Why are there duplicate PPIs in the dataset?

Some datasets include technical replicates, often for the wild-type (“WT”) or parent sequence in mutation studies. Replicates help capture the experimental and biological variation in measured affinities. This can be useful for analyses that assess the statistical significance of observed affinity difference, such as identifying how much a vaiant changes binding strength relative to a parent protein.

### What is considered a strong or good binder?

Affinity measurements are reported in log10 Kd nM (a value of 0 indicates 1 nM, 3 is 1 uM, 5 is 100 uM). Lower values indicate stronger binding. In practice, we often compare relative affinities - for example, assessing differences in binding strength as a target interface is mutated, or comparing variant binders to their parent.

### The dataset has NaN values in the affinity, why?

Not all PPIs form detectable interactions; weak or non-binding interactions may result in no paired barcode reads, yielding NaN values. For these cases, it may be more useful to look at the lower or upper bound affinities to help interpret the range of possible affinity within the assay.

### How should I cite this dataset?

Please cite:
A-Alpha Bio (2025). Open Protein–Protein Interaction Affinity Datasets. https://huggingface.co/aalphabio

### Can I use this dataset for model training or benchmarking?

Yes — the dataset is released fully open source, and is suitable for both academic and commercial use.

### Who can I contact with questions or feedback?

Feel free to email maintainers [Natasha Murakowska](mailto:nmurakowska@aalphabio.com) or [David Noble](mailto:dnoble@aalphabio.com). We will host a discussions tab for open discourse as well.