Wellcome Sanger Institute

Stem Cell Informatics

Scientific Operations

Stem Cell Informatics (SCI) develops custom laboratory information systems (LIMS) and computational research tools (WGE) for high-throughput laboratory analysis of human stem cells.

We are a small, focussed research group providing software development and bioinformatics facilites to the Stem Cell Engineering group. We also support he bespoke stem cell engineering team, which does not rely on LIMS systems so much owing of the nature of their work.

What do we produce?

The most visible aspect of our work is the public reporting available to everyone in LIMS2

There you can see a summary of clones targeted in our human and mouse stem cell experiments. Clicking on the linked numbers takes you to drill-down reports for more information including alignments, trace files and a host of other relevant data.

Tracking Software

Our software development is mainly done in Modern Perl, with significant portions of JavaScript. Our current LIMS systems is LIMS2, which is a successor to the HTGT (High-Throughput Gene Targeting) informatics system, which supports only the tracking of mouse clones and is now a legacy system. In LIMS2, we track clones from both mouse and human species. Most of the tracking in LIMS2 is related to human clones.

We provide 3-tier webapp support, using the Model-View-Controller design pattern exclusively for functional separation. The system is backended by a PostgreSQL relational database. LIMS2 tracks clones using a directed acyclic graph, which is stored in the database and access through the model layer of our webapp.

Quality control is managed by the web application and by supporting scripts, which us the parallele processing capabilities of the linux farm available at the Sanger Institute.

WGE – CRISPR database for genome editing

This valued research tools is described in detail on our WGE tool page. This tool is implemented in Perl, JavaScript and C++.

Other tools

We provide tools for oligo order generation, sanger sequencing submission and review, CRISPR damage analysis and integration of standard tickecting systems for production narrative.

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                            [post_title] => Parry-Smith, David
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                            [post_title] => Gene Editing
                            [post_excerpt] => In collaboration with our colleagues in Cellular Operations and Stem Cell Informatics, our work focuses on supporting and delivering the gene&nbsp;<span title="... editing requirements of the Institute's faculty and research programmes. Through the adoption and implementation of modern genome editing techniques, we tailor our technical experience to help answer biological questions. We optimise, develop and democratise the delivery of genome editing tools and platforms for the Institute&rsquo;s research programmes. For our collaborating partners we provide an agile, project focused, cost effective and efficient service as well as develop and provide biological resources, technical support and training for research groups and their staff.">...</span>
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                            [post_title] => High throughput gene editing
                            [post_excerpt] => The High Throughput Gene Editing team helped to deliver the gene editing requirements of the Institute's faculty and research
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    [introduction] => Stem Cell Informatics (SCI) develops custom laboratory information systems (LIMS) and computational research tools (WGE) for high-throughput laboratory analysis of human stem cells.
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                            [post_title] => Informatics and Software Development
                            [post_excerpt] => The Scientific Operations Informatics and Software Development teams provide essential support to the Sanger Institute's core platforms of sequencing, <span title="... cell biology and rodent models.">...</span>
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                            [post_date] => 2015-09-30 13:47:31
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                            [post_content] => <p>This tool was developed by Bill Skarnes (Faculty - Stem Cell Engineering), Vivek Iyer, Alex Hodgkins, Saj Perera, David Parry-Smith, Tiago Grego and Anna Farne (Stem Cell Informatics)</p><h5>General Introduction</h5><p>WGE is a highly interactive, web-based visual tool that employs an embedded genome browser and database to assist scientists in designing genome editing strategies using the CRISPR/Cas9 system.</p><p>Genome editing is the science of altering specific portions of DNA so that it behaves in a subtly different way within a cell. For example, we can use genome editing to prevent specific genes from being translated and subsequently transcribed into functioning proteins. In this way we can examine the role genes play in the life of the cell, potentially shedding valuable light on the causes of disease.</p><p>Proteins are the workhorse molecues of the cell, they provide physical structure to cells as well as carrying out work by ensuring chemical reactions occur in the right order, using the correct amount of energy and the appropriate ancillary molecules. Even a single unit of a protein, known as an amino acid residue, that is wrong can lead to debilitating disease. For example, <a href="https://en.wikipedia.org/wiki/Sickle-cell_disease#Genetics" target="_blank" rel="noopener noreferrer">sickle cell anaemia</a> is due to a single amino acid change that makes haemoglobin too sticky.</p><p>DNA is the molecule that carries the genetic code that specifies the sequence of amino acid resides in the protein products of the cell. It also carries a lot of information in non amino acid encoding regions that guides the way genes are expressed. Any of these regions could be the targets for genome editing campaigns.</p><h5>Detailed Description</h5><p>The rapid development of CRISPR-Cas9 mediated genome editing techniques has given rise to a number of online and stand-alone tools to find and score CRISPR sites for whole genomes. The Wellcome Trust Sanger Institute Genome Editing database (WGE), uses novel methods to compute, visualize and select optimal CRISPR sites in a genome browser environment. The WGE database currently stores single and paired CRISPR sites and pre-calculated off-target information for CRISPRs located in the mouse and human exomes. Scoring and display of off-target sites is simple, and intuitive, and filters can be applied to identify high-quality CRISPR sites rapidly. WGE also provides a tool for the design and display of gene targeting vectors in the same genome browser, along with gene models, protein translation and variation tracks. WGE is open, extensible and can be set up to compute and present CRISPR sites for any genome. <a href="http://www.ncbi.nlm.nih.gov/pubmed/25979474" target="_blank" rel="noopener noreferrer"><cite>[Hodgkins et al., 2015]</cite></a></p><p>The WGE website presents two tools for assisting genome editing:</p><ul><li>a CRISPR finder</li><li>a Gibson assembly PCR oligo designer</li></ul><p>The CRISPR-finding part of the WGE website requires the user to select a species&mdash;currently human or mouse&mdash;and the marker symbol of the gene to inspect. The target Ensembl exon is then selected from a list. All possible CRISPR sites and paired sites are shown on a scrollable Genoverse genome browser view. This incorporates the current gene models from Ensembl, protein translation, available variation and any user-generated targeting vector designs. &lsquo;Paired&rsquo; CRISPR sites for applications using Cas9 nickases are shown in WGE when CRISPR sites on opposite strands have a separation of up to 30&thinsp;bp, or an overlap of up to 10&thinsp;bp. <a href="http://www.ncbi.nlm.nih.gov/pubmed/24584192" target="_blank" rel="noopener noreferrer"><cite>[Shen et al., 2014]</cite></a></p><h6>Scoring Off-targets</h6><p>Our scoring system reports the number of similar sequences in the genome with up to four mismatches (excluding the PAM region). A string such as &lsquo;0:1, 1:0, 2:0, 3:4, 4:56&rsquo; indicates that there is 1 genomic site with 0 mismatches (the CRISPR site itself), no off-target sites with 1 or 2 mismatches, and an increasing number of potential off-target sites with 3 and 4 mismatches. In this way, users can immediately grasp the off-target potential for each CRISPR site.</p><p>Users can also filter CRISPR sites based on their stored off-target characteristics. Using this interface, hundreds of possible CRISPR sites can be narrowed down and evaluated to select the optimal site(s) for an editing task.</p><h6>Gibson Assembly Designer</h6><p>WGE can be used to design PCR primers for the assembly of gene targeting vectors by Gibson assembly or other similar PCR-based methods. This involves first choosing a target exon, and then adjusting design parameters via a web interface to allow the primer calculations to be run. The resulting targeting vector designs can be bookmarked, edited, and are displayed alongside CRISPR sites in the genome browser.</p><p>WGE contains comprehensive help and an application programming interface that enables users to build their own CRISPR indexes for specific projects.</p><p>See the publications below for further details.</p>
                            [post_title] => WGE - CRISPR design tool
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                                    [post_title] => Rein, Joel
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                                    [post_title] => Sampher, Beth
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                    [content] => <p>We are a small, focussed research group providing software development and bioinformatics facilites to the Stem Cell Engineering group. We also support he bespoke stem cell engineering team, which does not rely on LIMS systems so much owing of the nature of their work.</p>
<h4>What do we produce?</h4>
<p>The most visible aspect of our work is the public reporting available to everyone in <a href="https://lims2.stemcell.sanger.ac.uk/">LIMS2</a></p>
<p>There you can see a summary of clones targeted in our human and mouse stem cell experiments. Clicking on the linked numbers takes you to drill-down reports for more information including alignments, trace files and a host of other relevant data.</p>
<h4>Tracking Software</h4>
<p>Our software development is mainly done in Modern Perl, with significant portions of JavaScript. Our current LIMS systems is LIMS2, which is a successor to the HTGT (High-Throughput Gene Targeting) informatics system, which supports only the tracking of mouse clones and is now a legacy system. In LIMS2, we track clones from both mouse and human species. Most of the tracking in LIMS2 is related to human clones.</p>
<p>We provide 3-tier webapp support, using the Model-View-Controller design pattern exclusively for functional separation. The system is backended by a PostgreSQL relational database. LIMS2 tracks clones using a directed acyclic graph, which is stored in the database and access through the model layer of our webapp.</p>
<p>Quality control is managed by the web application and by supporting scripts, which us the parallele processing capabilities of the linux farm available at the Sanger Institute.</p>
<h4>WGE &#8211; CRISPR database for genome editing</h4>
<p>This valued research tools is described in detail on our <a href="https://www.sanger.ac.uk/tool/wge/">WGE tool page</a>. This tool is implemented in Perl, JavaScript and C++.</p>
<h4>Other tools</h4>
<p>We provide tools for oligo order generation, sanger sequencing submission and review, CRISPR damage analysis and integration of standard tickecting systems for production narrative.</p>
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    [page_url] => https://www.sanger.ac.uk/group/stem-cell-informatics/
    [page_title] => Stem Cell Informatics
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    [post_url] => https://www.sanger.ac.uk/group/stem-cell-informatics/
    [post_title] => Stem Cell Informatics
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    [post_status] => publish
    [created_at] => 2015-10-16 13:09:46
    [updated_at] => 2020-06-22 10:54:25
    [custom_credit] => Wellcome Sanger Institute
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                            [post_title] => Gene Editing
                            [post_excerpt] => In collaboration with our colleagues in Cellular Operations and Stem Cell Informatics, our work focuses on supporting and delivering the gene&nbsp;<span title="... editing requirements of the Institute's faculty and research programmes. Through the adoption and implementation of modern genome editing techniques, we tailor our technical experience to help answer biological questions. We optimise, develop and democratise the delivery of genome editing tools and platforms for the Institute&rsquo;s research programmes. For our collaborating partners we provide an agile, project focused, cost effective and efficient service as well as develop and provide biological resources, technical support and training for research groups and their staff.">...</span>
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                            [post_title] => High throughput gene editing
                            [post_excerpt] => The High Throughput Gene Editing team helped to deliver the gene editing requirements of the Institute's faculty and research
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                            [post_name] => high-throughput-gene-editing
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Core team

Photo of Mr Peter Keen

Mr Peter Keen

Software Developer

Photo of Joel Rein

Joel Rein

Senior Software Developer

Previous team members

Photo of Mr Joshua Kent

Mr Joshua Kent

Sandwich Year Placement

Photo of Tiago Grego

Tiago Grego

Software Developer

Photo of David Adeniji

David Adeniji

Student Placement