Integrative computational and systems biology approaches for deciphering cellular regulomes that promote carcinogenesis
Lead Research Organisation:
University of Cambridge
Department Name: UNLISTED
Abstract
It is becoming easier to generate large cancer related datasets. However the methods to understand these and to extract meaningful, biologically relevant readouts from these data sets is underdeveloped. We are developing computational and statistical tools, methods and resources to integrate, mine, model and visualize these complex data-sets and convert them into a format that can advance our knowledge of cancer biology. This will enable a better comprehension of the circuitry involved in tumour formation, disease progression and metastasis, and can be applied to the development of targeted therapeutics.
Technical Summary
Numerous genetic aberrations affecting a large number of gene products contribute to tumour development and the accepted hallmarks of cancer, often making therapies based on single targets ineffective. These aberrations and their consequences are propagated via transcriptional, translational and post-translational networks. The resultant information circuits can extend across cell and tissue types and also modulate the microenvironment. How to integrate and model this percolation of information and properties across different biological scales, in both time and space is accepted as a major challenge to fully understanding the aetiology, progression and dynamics of tumorigenesis. Novel computational methods, tools and resources are essential to address this challenge.
Transcriptomic and copy number assessment studies suggest that specific sets of key pathways that regulate cellular phenotypes are pathologically altered in cancer. However, pathway centric approaches are not completely effective because pathways don’t operate in isolation; instead, multiple interacting pathways form a complex web of networks. Methods to decipher cellular information flows (whether they are signalling, metabolic or regulatory) can shed light on the underlying cellular complexity and identify systems level properties. The objective of this research programme is therefore to develop a network perspective of tumorigenesis using a mixture of both integrative data driven as well as computational modelling approaches.
The programme harnesses data science approaches coupled with computational and systems biology methodologies to develop novel methods, tools and resources for systems level biomedical data-integration. It addresses these objectives by 1) modelling multi-scale cellular regulomes involved in tumorigenesis, 2) developing these model into knowledge discovery systems to assist in understanding of cancer datasets, and 3) Using these resources to elucidate phenotypic impact and identify therapeutic intervention points of these regulomes for further experimental evaluation.
Transcriptomic and copy number assessment studies suggest that specific sets of key pathways that regulate cellular phenotypes are pathologically altered in cancer. However, pathway centric approaches are not completely effective because pathways don’t operate in isolation; instead, multiple interacting pathways form a complex web of networks. Methods to decipher cellular information flows (whether they are signalling, metabolic or regulatory) can shed light on the underlying cellular complexity and identify systems level properties. The objective of this research programme is therefore to develop a network perspective of tumorigenesis using a mixture of both integrative data driven as well as computational modelling approaches.
The programme harnesses data science approaches coupled with computational and systems biology methodologies to develop novel methods, tools and resources for systems level biomedical data-integration. It addresses these objectives by 1) modelling multi-scale cellular regulomes involved in tumorigenesis, 2) developing these model into knowledge discovery systems to assist in understanding of cancer datasets, and 3) Using these resources to elucidate phenotypic impact and identify therapeutic intervention points of these regulomes for further experimental evaluation.
Organisations
People |
ORCID iD |
Shamith Samarajiwa (Principal Investigator) |
Publications
Kirschner K
(2015)
Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53.
in PLoS genetics
Hu Z
(2016)
Genome co-amplification upregulates a mitotic gene network activity that predicts outcome and response to mitotic protein inhibitors in breast cancer.
in Breast cancer research : BCR
Turrell FK
(2017)
Lung tumors with distinct p53 mutations respond similarly to p53 targeted therapy but exhibit genotype-specific statin sensitivity.
in Genes & development
Rodrigues P
(2018)
NF-?B-Dependent Lymphoid Enhancer Co-option Promotes Renal Carcinoma Metastasis.
in Cancer discovery
Shorthouse D
(2018)
Exploring the role of stromal osmoregulation in cancer and disease using executable modelling.
in Nature communications
Parry AJ
(2018)
NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence.
in Nature communications
Related Projects
Project Reference | Relationship | Related To | Start | End | Award Value |
---|---|---|---|---|---|
MC_UU_12022/4 | 01/10/2013 | 31/03/2018 | £882,000 | ||
MC_UU_12022/5 | Transfer | MC_UU_12022/4 | 01/10/2013 | 31/03/2022 | £1,713,000 |
MC_UU_12022/6 | Transfer | MC_UU_12022/5 | 01/10/2013 | 31/03/2022 | £2,157,000 |
MC_UU_12022/7 | Transfer | MC_UU_12022/6 | 01/10/2013 | 31/03/2022 | £2,147,000 |
MC_UU_12022/8 | Transfer | MC_UU_12022/7 | 01/10/2013 | 31/03/2022 | £5,896,000 |
MC_UU_12022/9 | Transfer | MC_UU_12022/8 | 01/10/2014 | 31/03/2022 | £869,000 |
MC_UU_12022/10 | Transfer | MC_UU_12022/9 | 01/01/2015 | 31/03/2022 | £987,000 |
Title | "Through the eyes of scientists" |
Description | Photography exhibition at the Cambridge Science Festival 2015 |
Type Of Art | Artistic/Creative Exhibition |
Year Produced | 2015 |
Impact | Interactions with the general public |
URL | http://www.sciencefestival.cam.ac.uk/system/files/csf_2015_web_programme.pdf |
Title | Collaboration with an artist to produce a sculpture of a neural network |
Description | Collaboration with an artist to produce a sculpture of a neural network |
Type Of Art | Artwork |
Year Produced | 2019 |
Impact | public interest in neural networks |
Description | Organised and implemented computational biology and genome technologies training courses for biomedical researchers |
Geographic Reach | National |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Improved complex and large data-set analysis of both local, national and international biomedical researchers. Provides free training material updated as methods and technologies change. |
Description | Organised and implemented the CRUK Bioinformatics Autumn School in Functional Genomics |
Geographic Reach | National |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Trained cancer researchers from UK wide in latest data analysis and interpretation methods in functional genomics. |
URL | http://bioinformatics-core-shared-training.github.io/cruk-bioinf-sschool/ |
Description | Organised and implemented the CRUK Bioinformatics Summer School in Functional Genomics |
Geographic Reach | National |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Trained current and future scientist in technologies and methods used for analysis of cancer and functional genomic datasets |
URL | https://bioinformatics-core-shared-training.github.io/cruk-summer-school-2018/ |
Description | Isaac Newton Trust / Wellcome Trust ISSF / University of Cambridge Joint Research Grants Scheme |
Amount | £85,000 (GBP) |
Organisation | University of Cambridge |
Department | Isaac Newton Trust |
Sector | Academic/University |
Country | United Kingdom |
Start | 04/2018 |
End | 08/2021 |
Title | Pangaea |
Description | A natural language processing method to text-mine gene regulatory relationships from the 30 million articles in PubMed. |
Type Of Material | Technology assay or reagent |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | Currently a preprint. |
URL | https://github.com/ss-lab-cancerunit/pangaea |
Title | SpiderSeqR |
Description | Data search and collection software for biomedical sequencing data from NCBI GEO and SRA repositories. |
Type Of Material | Technology assay or reagent |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Currently a preprint |
URL | https://github.com/ss-lab-cancerunit/SpiderSeqR |
Title | Pangaea: a software package for natural language processing |
Description | Python package for text mining entity-relationships from literature |
Type Of Technology | Software |
Year Produced | 2020 |
Impact | None yet. |
Title | SpiderSeqR: Software package to search and collect specific sequencing data sets |
Description | search and collection of sequencing related Big Data |
Type Of Technology | Software |
Year Produced | 2020 |
Open Source License? | Yes |
Impact | Not Yet |
Description | "The big data revolution" Epigenetics: more than just our genes" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Public lectures "The big data revolution" Epigenetics: more than just our genes" at the institute of continuing education |
Year(s) Of Engagement Activity | 2019 |
Description | BBC digital planet interview, "AI and big data in cancer research" |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | BBC digital planet interview, "AI and big data in cancer research" - Interview on how AI is used in cancer research. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.bbc.co.uk/sounds/play/w3csy668/ |
Description | Cambridge Big Biology day |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Science festival organised by the Hills road secondary college, Cambridge. |
Year(s) Of Engagement Activity | 2019 |
Description | Cambridge Science Festival |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | We also participated in the Cambridge Science Festival where my group set up an exhibit consisting of multiple electronic sensor technologies, programmable Lego robots, Raspberry Pi computers to explain some of our research |
Year(s) Of Engagement Activity | 2019 |
Description | MRC-CU open day |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Open day where sixth form students from local schools get to meet cancer researchers from all career stages |
Year(s) Of Engagement Activity | 2019 |
Description | MRC-CU open day |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Sixth-form students from across schools in Cambridge visited the MRC Cancer Unit on the afternoon of the 19th of June, 2018 for an Open Day. All students, accompanied by their teachers, were given a tour of the entire building with an opportunity for engaging with researchers about the state of the art in cancer research and gaining hands-on experience with setting up experiments. Talks about career opportunities and challenges associated with pursuing cancer research were also available to all attendees. The event sparked a great deal of interest and enthusiasm in students and teachers alike and we have had a request for this event to be continued. We will be pursuing a similar format of activities for the MRC Science Festival in 2018, but reach out to more number of schools, including those outside of Cambridge city perimeters. |
Year(s) Of Engagement Activity | 2018 |
Description | Participation in Cambridge University Science Festival (2015,2016, 2017, 2018) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | The Cambridge Science Festival aims to reach out to the general public and communicate about the different aspects of science and research being undertaken at the University. It is a free event, over two weeks, with an excess of 270 events and more than 30000 attendees. As part of this, the MRC CU along with the CRUK CI organised a set of talks and hands- on activities that are attended by over 100 people from all walks of life - from young children and young adults to parents/carers and professionals. The Samarajiwa lab were an active part of the MRC CU team at this event over the last couple of years. The event generated a lot of interest in cancer research, helps raise awareness about the importance of 'early' in cancer which is the mission of the MRC CU and also led to a lot of interest being generated in the MRC Festival of Science which followed on later in the year. |
Year(s) Of Engagement Activity | 2015,2016,2017,2018 |
URL | https://www.mrc-cu.cam.ac.uk/PublicEngagement/publicengagementhighlights |
Description | Participation in MRC Festival of Science Open Day at MRC CU |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | 60 sixth-form students from across 8 schools in Cambridge visited the MRC Cancer Unit on the afternoon of the 22nd of June, 2016 for an Open Day. All students, accompanied by their teachers, were given a tour of the enitre building with an opportunity for engaging with researchers about the state of the art in cancer research and gaining hands-on experience with setting up experiments. Talks about career opportunities and challenges associated with pursuing cancer research were also available to all attendees. The event sparked a great deal of interest and enthusiasm in students and teachers alike and we have had a request for this event to be continued. We will be pursuing a similar format of activities for the MRC Science Festival in 2017, but reach out to more number of schools, including those outside of Cambridge city perimeters. |
Year(s) Of Engagement Activity | 2016 |
URL | https://mrccancerunit.wordpress.com/2016/07/06/inspiring-the-next-generation-of-cancer-researchers-t... |
Description | Participation in an activity, workshop or similar - Participation in Cambridge University Science Festival |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Used raspberry pi computers, algorithms and lego robots to demonstrate how personalised medicine works in cancer. |
Year(s) Of Engagement Activity | 2018 |
Description | Public Talk "Data Science Approaches for Cancer Epigenomics" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | More than 50 people from industry, academia, students and general public attended. the concepts were new to them and sparked many interesting discussions. |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.meetup.com/Cambridge-Genomics-Meetup-Group/events/267203886/ |
Description | Public Talk at Pint of Science Cambridge "Can AI help in the fight against cancer?" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Public talk atint of Science Cambridge "Can AI help in the fight against cancer?" in 2019, including a collaboration with a local artist resulting in a sculpture of a deep neural network. |
Year(s) Of Engagement Activity | 2019 |
URL | https://pintofscience.co.uk/event/how-deep-is-your-learning |
Description | Public talk "Data Science Approaches for Cancer Epigenomics" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Public talk at the Cambridge genomics and AI meetup "Data Science Approaches for Cancer Epigenomics" |
Year(s) Of Engagement Activity | 2020 |
URL | https://www.meetup.com/Cambridge-Genomics-Meetup-Group/events/267203886/ |
Description | Public talk at Cambridge Science Festival "Artificial intelligence assisted discovery in the battle against cancer and other diseases" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Talk at the Cambridge Science Festival -"Artificial intelligence assisted discovery in the battle against cancer and other diseases" |
Year(s) Of Engagement Activity | 2019 |
Description | Public talk at the Cambridge science festival. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | talk title: Battling cancer with data science |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.cambridgecancercentre.org.uk/news/cancer-talks-cambridge-science-festival |
Description | The Application of Artificial Intelligence and Data Science in Biomedicine |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Public talk on AI in biomedicine with examples of some work done by my group to a public audience. |
Year(s) Of Engagement Activity | 2021 |
Description | Working life blog for MRC Insight |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Contributed to a blog article which featured in MRC Insight. This was a working life blog, in which I discussed my career path to date, my research interests, and the importance of bioinformatics and data science in understanding the complex steps of carcinogenesis. This article was very well publicised on social media platforms (twitter, facebook) and raised awareness of the current research, as well as the impact of data science on cancer research efforts. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.insight.mrc.ac.uk/2016/02/12/working-life-dr-shamith-samarajiwa/ |