Zebrahub: Illuminating Zebrafish Embryogenesis By means of Gentle-Sheet Microscopy and scRNA Sequencing.


Gentle-sheet time-lapse of Tg(h2afva:h2afva-mcherry ; mezzo:eGFP) embryo beginning at 50% epiboly.

What’s Zebrahub?

Zebrahub is a web-based platform that gives an built-in strategy to learning and analyzing mobile lineages throughout zebrafish embryogenesis at each transcriptional and spatiotemporal ranges. It combines single-cell sequencing time course information with lineage reconstructions facilitated by light-sheet microscopy. The scRNAseq gene expression throughout tissues and time factors may be instantly visually explored in an internet browser.  Moreover, researchers can navigate the complicated mobile flows and lineages derived from light-sheet microscopy information utilizing Zebrahub’s on-line net viewer and desktop interactive device, enabling exploration of complete timelapse datasets and digital destiny mapping experiments.

What impressed the event of Zebrahub?

Once we initiated the challenge, it was clear that the neighborhood was lacking a database combining systematic live-imaging-based cell lineages with single-cell sequencing throughout growth. Historically these approaches have been used individually, thereby limiting the total understanding of growth. We needed to make use of probably the most superior microscopy and sequencing strategies accessible to ascertain a multimodal baseline of zebrafish growth.

How can scientists make the most of Zebrahub of their analysis?

Many necessary discoveries in developmental biology originated from observations; due to this fact, from the start, we needed to have a totally interactive web site to empower scientists by making our information accessible and, extra importantly, instantly explorable, even to scientists with out coding abilities.  Thus, regarding our terabyte-scale high-resolution light-sheet imaging time-lapse dataset, we offer each an neuroglancer-based interactive viewer for complete multi-color time-lapse datasets and a napari plugin to carry out in silico destiny mapping experiments.  Equally, we enable researchers to effortlessly seek for particular gene expressions and the emergence of cell varieties utilizing CZI’s cell-by-gene platform. Our dedication to accessibility led us to take a position substantial effort in making certain that our information, code, and blueprints are available and open supply. By doing so, we anticipate an instantaneous affect on a wide-ranging neighborhood, spanning disciplines akin to developmental biology, single-cell biology, superior microscopy, laptop imaginative and prescient, tissue morphodynamics, and computational biology.

Who’re the individuals behind this useful resource?

People behind this resource

Supported by the CZ Biohub San Francisco (CZB-SF), Zebrahub is led by Merlin Lange,  senior scientist within the lab of Loic Royer, and outcomes from an interdisciplinary collaboration with CZB’s Information Science and Genomics Platforms, with key contributors amongst others: Angela Oliveira Pisco, Norma Neff, and Alejandro Granados. Total, Zebrahub has greater than 30 collaborators at CZB-SF collaborating establishments (see image above). Many are early-career scientists who performed a key function within the challenge. Within the following, these younger scientists introduce themselves and their contributions:

Shruthi : I’m Shruthi VijayKumar, a analysis affiliate within the Royer lab. A major a part of my function concerned growing and optimizing the only embryo single cell dissociation protocol for the varied developmental levels in zebrahub together with Michael Borja (Genomics) and Merlin Lange. Moreover, I contributed to getting ready the libraries required for sequencing and helped with cell annotations. This challenge has been an unbelievable expertise, because it has supplied me with the chance to work in a multidisciplinary and collaborative surroundings. This expertise has not solely given me a greater understanding of your complete pipeline but additionally broadened my experience by way of in depth interactions with totally different groups. The truth that Zebrahub is an increasing useful resource for the neighborhood makes this challenge much more particular and rewarding to be part of.

Sarah: My identify is Sarah Ancheta, and I’m an affiliate Information Scientist. As a part of the Zebrahub staff, I labored on information processing and evaluation of inter-individual transcriptomic variability. Since Zebrahub has single-cell transcriptomic datasets from individually resolved embryos, I used to be in a position to dissect the embryo-to-embryo variability by growing a framework to research the variations in gene expression between sibling people over time. I really feel lucky to work with information of such top quality and backbone and excited to have been among the many first to research Zebrahub’s information and discover new organic insights into zebrafish growth. It has been an exquisite expertise to work with such an interdisciplinary staff and be taught to conduct analyses from each a organic and data-driven perspective.

Mike: My identify is Michael Borja, and I’m a Senior Analysis Affiliate for the Genomics platform. My fundamental function and duty is to supervise lab actions concerning Single Cell and Spatial Transcriptomic experiments. When Zebrahub initially began, I used to be tasked with choosing which single-cell transcriptomic assay to make use of for our preliminary experiments. From there, I led the early efforts of processing cell dissociations and library preparation of particular person embryos. As well as and in partnership with Shruthi VijayKumar, we developed a sturdy zebrafish single-cell dissociation protocol from single embryos that’s unbiased of the developmental stage. Being a part of this multidisciplinary and modern staff has helped me see how large-scale initiatives inside the realm of science may be idealized and accomplished. As I proceed with my private development and path within the discipline of Genomics, I’ll completely proceed to hunt large-scale collaborations akin to Zebrahub in order that I might be able to apply what I’ve discovered by way of this expertise. 

Jordao: My identify is Jordao Bragantini. I’m a software program engineer within the Royer lab. My main focus revolves round picture processing, cell segmentation, and monitoring. The Zebrahub challenge uncovered me to the fascinating world of terabyte-scale microscopy pictures in addition to to the mysteries of Developmental Biology. Dealing with this huge quantity of knowledge acquired on our superior light-sheet microscopes required implementing specialised algorithms, starting from GPU-friendly approximate morphological operators to our personal distributed monitoring software program. These analyses require the total capability of our accessible computational assets. I couldn’t have wished for a greater strategy to have interaction with machine studying within the biology area than working with this multidisciplinary staff, the place we are able to be taught from one another’s experience.

What are the subsequent steps for Zebrahub?

We need to develop Zebrahub with extra developmental levels, novel multiomic modalities, and extra lineage-specific imaging to in the end reconstruct a digital multimodal embryo. We’re additionally engaged on integrating present datasets, together with these from various species, to create a complete atlas of vertebrate embryogenesis. This formidable endeavor heralds a transformative period for the fields of developmental and evolutionary biology.

You possibly can learn extra about Zebrahub within the BioRxiv preprint.

NMP centered RNA velocity UMAP (static)

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