(1/13) Excited to share the outcome of the IBIS Challenge! The IBIS challenge united dozens of teams across the world in tackling the problem of modeling transcription factor (TF) binding specificity using a diverse collection of experimental datasets for understudied human TFs.

Our paper on LARGE-scale benchmarking of motif discovery tools is published! nature.com/articles/s42... It was a long, 7 years long journey, which coordinated efforts of 50+ researchers, proud to be on of them. More results from Codebook about poorly studied TFs are coming soon.

Cross-platform motif discovery and benchmarking to explore binding specificities of poorly studied human transcription factors - Communications Biology

Cross-platform benchmarking of DNA binding specificity models highlights top-performing motif discovery methods and demonstrates the potential of advanced models to capture alternative binding modes o...

nature.com

Vanja@halfacrocodile.bsky.social · 2y ago

(1/12) Excited to present the results of the large-scale benchmarking of DNA motif discovery tools using the Codebook data compendium on poorly studied human transcription factors and the Codebook Motif Explorer: dx.doi.org/10.1101/2024..., mex.autosome.org ⬇️.

(12/12) Kudos to the Codebook and GRECO-BIT consortium members including @bartdeplancke.bsky.social, see the whole team at ibis.autosome.org/docs/about_us

(11/12) This project is only one of the multiple facets of the larger Codebook initiative, check dx.doi.org/10.1101/2024...

(10/12) Want something more than simple PWMs? Reaching the next level with IBIS: join the online IBIS conference on November 27, more details soon at ibis.autosome.org.

(9/12) Check the interactive Codebook/GRECO-BIT Motif Explorer (mex.autosome.org), which provides motifs, performance metrics, ranks, logos, top-performing motifs, and structured metadata.

(8/12) With that many PWMs at hand, we also demonstrate that several motifs can be easily combined into a better model with ArChIPelago: regression or Random Forest on top of PWM scans.

(7/12) Comparison of different tools yielded many surprises. On the one hand, underused motif discovery tools such as Dimont excel across different types of experimental data. On the other hand, no single tool or platform is enough to get the most for each TF and each data type.

(6/12) In total, we processed data from 4,237 experiments and generated 219,939 motifs. 164,350 motifs (for 236 TFs) from curated and approved datasets were taken for benchmarking. The motifs and datasets are available at ZENODO zenodo.org/records/1018....

(5/12) Testing all existing tools is hardly realistic. Focusing on position weight matrices (PWMs), we tested the most popular tools (e.g. MEME, HOMER), less popular yet powerful tools (e.g. ChIPMunk, Dimont), and a few advanced methods still able to yield PWMs (e.g. ExplaiNN, ProBound).

(4/12) We aimed to tackle both problems by running multiple motif discovery software against a large set of newly generated DNA on human TF-DNA interactions from Codebook [https://dx.doi.org/10.1101/2024.11.11.622097].

(3/12) There are a multitude of high-throughput methods for assessing the DNA binding specificity of transcription factors. The variety of existing motif discovery tools is even greater. Which one to use?

(2/12) The human genome encodes ~1.5 thousand transcription factors (TFs), and hundreds of them still lack "DNA motifs", i.e., compact human- and machine-readable representations of the TF-DNA binding specificity.

(1/12) Excited to present the results of the large-scale benchmarking of DNA motif discovery tools using the Codebook data compendium on poorly studied human transcription factors and the Codebook Motif Explorer: dx.doi.org/10.1101/2024..., mex.autosome.org ⬇️.

(7/7) Kudos to the Codebook and GRECO-BIT consortium members including ‪@halfacrocodile.bsky.social‬ and @bartdeplancke.bsky.social. See the whole team at ibis.autosome.org/docs/about_us

(6/7) 1,421 human TFs now have a characterized DNA-binding specificity, and nearly all 1,638 have been assayed. Analyses in doi.org/10.1101/2024... indicate, however, that many previously characterized TF binding specificities may be inaccurate.

(5/7) Collectively the uncharacterized TFs bind directly to tens of thousands of conserved sequences, providing biochemical functions for these sites. Intriguingly, many of these sites are in genomic “dark matter”. Explored further in doi.org/10.1101/2024...

(4/7) Methods for PWM discovery and benchmarking are explored in detail in an accompanying manuscript: doi.org/10.1101/2024...

(3/7) Of the 332 uncharacterized TFs, PWMs were identified for 177, the vast majority of which have unique and previously unseen motifs.

(2/7) We applied five different assays to 332 uncharacterized TFs (i.e., Codebook TFs) and 61 control TFs, including a new assay, GHT-SELEX, described in: doi.org/10.1101/2024...

(1/7) Thrilled to reveal the results of the Codebook Project, an international effort to identify accurate DNA-binding motifs and genomic binding loci for the >300 uncharacterized human transcription factors (TFs) doi.org/10.1101/2024...

Perspectives on Codebook: sequence specificity of uncharacterized human transcription factors

We describe an effort (“Codebook”) to determine the sequence specificity of 332 putative and largely uncharacterized human transcription factors (TFs), as well as 61 control TFs. Nearly 5,000 independ...

doi.org

Last but not least: this update became possible thanks to the experimental data & motif analysis performed within the Codebook/GRECO-BIT collaboration, ibis.autosome.org/docs/about_us

(4/4) Don't hesitate to grab a fresh release from hocomoco.autosome.org and remember that we also provide a fancy online motif scanner, MoLoTool, in all its interactive JS-powered beauty.

(3/4) Also do not forget that HOCOMOCO also provides motifs for orthologous mouse TFs, >800 of those are covered in v13.

(2/4) v13 covers >1100 of ~1600 human TFs with >1600 primary motifs and subtypes. Since v12 we also provide a reduced non-redundant set of motifs, which are often shared between TFs with similar DBDs.

(1/4) Thrilled to announce another major release of the HOCOMOCO motif collection, well-known for its silly name and rigorous approach to constructing and benchmarking DNA sequence motifs recognized by human and mouse transcription factors. hocomoco.autosome.org