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Expand Up @@ -124,36 +124,25 @@ <h4>How to apply as a speaker</h4>
<p>The seminar is a great opportunity to present your recent work to a large international audience.
If you want to apply as a speaker, please use the contact in the registration confirmation email.</p>
<h4>Next seminar</h4>
<h6> Title: Single-cell multi-scale footprinting reveals the organization of cis-regulatory elements </h6> 4 September 2024 5:30 p.m. - 6:30 p.m. Central European Time
<p>Speaker: <strong><a href="https://www.buenrostrolab.com/">Max Horlbeck and Ruochi Zhang (Buenrostro lab)</a></strong>, Harvard University and Broad Institute</p>
<h6> Title: Decoding sequence determinants of gene expression in diverse cellular and disease states </h6> 2 October 2024 5:30 p.m. - 6:30 p.m. Central European Time
<p>Speaker: <strong><a href="https://avantikalal.github.io/">Avantika Lal</a></strong>, Genentech</p>
<strong>Abstract:</strong>
<p align="justify">
Cis-regulatory elements (CREs) control gene expression and are dynamic in their structure and function,
reflecting changes to the composition of diverse effector proteins over time1–3. However, methods for
measuring the organization of effector proteins at CREs across the genome are limited, hampering efforts to
connect CRE structure to their function in cell fate and disease. Here, we developed PRINT, a computational
method that identifies footprints of DNA-protein interactions from bulk and single-cell chromatin accessibility
data across multiple scales of protein sizes. Using these multi-scale footprints, we created the seq2PRINT
framework, which employs deep-learning to allow precise inference of transcription factor and nucleosome
binding and interprets regulatory logic at CREs. Applying seq2PRINT to single-cell chromatin accessibility
data from human bone marrow, we observe sequential establishment and widening of CREs centered on
pioneer factors across hematopoiesis. We further discover age-associated alterations in the structure of
CREs in murine hematopoietic stem cells, including widespread loss of nucleosomes and gain of de
novo-identified Ets composite motifs. Collectively, we establish a method for obtaining rich insights into
DNA-binding protein dynamics from chromatin accessibility data and reveal the architecture of regulatory
elements across differentiation and aging.
Sequence-to-function models that predict gene expression from genomic DNA sequence have proven valuable for many biological tasks, including understanding cis-regulatory syntax and interpreting non-coding genetic variants. However, current state-of-the-art models have been trained largely on bulk expression profiles from healthy tissues or cell lines, and have not learned the properties of precise cell types and cellular states that are captured in single-cell transcriptomic datasets. To address this gap, I will present Decima, a model that predicts the cell type- and condition- specific expression of a gene from its surrounding DNA sequence. Decima is trained on single-cell or single-nucleus RNA sequencing data from over 22 million cells, and successfully predicts cell type-specific expression profiles of unseen genes based on sequence alone. In this talk, I will demonstrate Decima’s ability to reveal the cis-regulatory mechanisms driving cell type-specific gene expression and disease responses, predict non-coding variant effects at high resolution, and design regulatory DNA elements with precisely tuned, context-specific functions.
</p>

<h4>Upcoming speakers</h4>
<div class="container-fluid">
<ul class="list-unstyled">
<li>2 October 2024 - <a href="https://avantikalal.github.io/">Avantika Lal</a>, Genentech</li>
<li>6 November 2024 - <a href="">TBD</a>, TBD</li>
<li>4 December 2024 - <a href="https://scholar.google.ru/citations?user=0f5hVB4AAAAJ&hl=en">Ivan Kulakovskiy, Dmitry Penzar</a>, Vavilov Institute of General Genetics</li>

</ul>
</div>
<h4>Previous speakers</h4>
<div class="container-fluid">
<ul class="list-unstyled">
<li>4 September 2024 - <a href="https://www.buenrostrolab.com/">Max Horlbeck and Ruochi Zhang (Buenrostro lab)</a>, Harvard University and Broad Institute</li>
<li>3 July 2024 - <a href="https://www.sabetilab.org/sager-gosai/">Sagar Gosai - Sabeti (Broad), Reilly (Yale) & Tewhey lab (Jackson laboratories)</a>, Broad Institute of Harvard and MIT</li>
<li>5 June 2024 - <a href="http://saramostafavi.github.io/">Sara Mostafavi</a>, University of Washington</li>
<li>8 May 2024 - <a href="https://www.instadeep.com/">Thomas Pierrot</a>, InstaDeep</li>
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