Andrew Blake

University of Oxford | OX · Department of Oncology

Response to neoadjuvant radiotherapy (RT) in rectal cancer has been associated with immune and stromal features that are captured by transcriptional signatures. However, how such associations perform across different chemoradiotherapy regimens and within individual consensus molecular subtypes (CMS) and how they affect survival remain unclear. In t...

The development of deep learning (DL) models to predict the consensus molecular subtypes (CMS) from histopathology images (imCMS) is a promising and cost-effective strategy to support patient stratification. Here, we investigate whether imCMS calls generated from whole slide histopathology images (WSIs) of rectal cancer (RC) pre-treatment biopsies...

Molecular stratification using gene-level transcriptional data has identified subtypes with distinctive genotypic and phenotypic traits, as exemplified by the consensus molecular subtypes (CMS) in colorectal cancer (CRC). Here, rather than gene-level data, we make use of gene ontology and biological activation state information for initial molecula...

Molecular stratification, across many tumour types, has used gene-level transcriptional data to identify subtypes associated with distinct genotypes and biological traits, as exemplified by the consensus molecular subtypes (CMS), and more recently the intrinsic CMS (iCMS), in colorectal cancer. In an attempt to develop molecular subtypes that more...

The development of deep learning (DL) models to predict the consensus molecular subtypes (CMS) from histopathology images (imCMS) is a promising and cost-effective strategy to support patient stratification. Here, we investigate whether imCMS calls generated from whole slide histopathology images (WSIs) of rectal cancer (RC) pre-treatment biopsies...

3577 Background: The use of cetuximab (cetux) with chemotherapy (chemo) in patients with operable liver metastases from colorectal cancer (CRC) conferred a survival disadvantage in New EPOC. Whilst genetic alterations such as emergent sub-clonal mutations in RAS/ BRAF, ERBB2 and MET are recognized as mechanisms of resistance to EGFR inhibition (EGF...

PURPOSE Outcomes in RAS-mutant metastatic colorectal cancer (mCRC) remain poor and patients have limited therapeutic options. Adavosertib is the first small-molecule inhibitor of WEE1 kinase. We hypothesized that aberrations in DNA replication seen in mCRC with both RAS and TP53 mutations would sensitize tumors to WEE1 inhibition. METHODS Patients...

p>Neoadjuvant chemoradiotherapy is commonly used to treat rectal cancer but patients have different levels of response and/or toxic effects. As part of the Stratification in COloRecTal cancer (S:CORT) programme, we collected 257 rectal biopsies from two cohorts: Grampian (single hospital) and Aristotle (clinical trial). All patients had been subse...

Abnormal CpG methylation in cancer is ubiquitous and generally detected in tumour specimens using a variety of techniques at a resolution encompassing single CpG loci to genome wide coverage. Analysis of samples with very low DNA inputs, such as formalin fixed (FFPE) biopsy specimens from clinical trials or circulating tumour DNA is challenging at...

Background: Abnormal CpG methylation in cancer is ubiquitous and generally detected in tumour specimens using a variety of techniques at a resolution encompassing single CpG loci to genome wide coverage. Analysis of samples with very low DNA inputs, such as formalin fixed (FFPE) biopsy specimens from clinical trials or circulating tumour DNA is cha...

Immunohistochemical quantification of the immune response is prognostic for colorectal cancer (CRC). Here, we evaluate the suitability of alternative immune classifiers on prognosis and assess whether they relate to biological features amenable to targeted therapy. Overall survival by immune (CD3, CD4, CD8, CD20 and FOXP3) and immune-checkpoint (IC...

Background: CpG methylation in cancer is ubiquitous and generally detected in tumour specimens using a variety of techniques at a resolution encompassing single CpG loci to genome wide. Analysis of samples with very low DNA inputs, such as formalin fixed (FFPE) biopsy specimens from clinical trials or circulating tumour DNA has been challenging and...

Objective Pathological Wnt pathway activation is a conserved hallmark of colorectal cancer. Wnt-activating mutations can be divided into: i) ligand-independent (LI) alterations in intracellular signal transduction proteins ( Adenomatous polyposis coli , β-catenin), causing constitutive pathway activation and ii) ligand-dependent (LD) mutations affe...

Background: The tumor microenvironment is a key feature to understand cancer biology and may be used clinically. Quantification of tissue composition is usually based either on visual pathological review (VPR) or deconvolution of whole genome molecular data. Although the former is a direct measurement it has modest reproducibility while the latter...

Background: The tumor microenvironment is a key feature to understand cancer biology and may be used clinically. Quantification of tissue composition is usually based either on visual pathological review (VPR) or deconvolution of whole genome molecular data. Although the former is a direct measurement it has modest reproducibility while the latter...

Image analysis is a cost-effective tool to associate complex features of tissue organisation with molecular and outcome data. Here we predict consensus molecular subtypes (CMS) of colorectal cancer (CRC) from standard H&E sections using deep learning. Domain adversarial training of a neural classification network was performed using 1,553 tissue se...

Objective Complex phenotypes captured on histological slides represent the biological processes at play in individual cancers, but the link to underlying molecular classification has not been clarified or systematised. In colorectal cancer (CRC), histological grading is a poor predictor of disease progression, and consensus molecular subtypes (CMSs...

Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, b...

Supplementary Figures 1-5 and Supplementary Tables 1-3

Gaze has been proposed as an ideal modality for supporting remote target selection. We explored the potential of integrating gaze with hand gestures for remote interaction on a large display in terms of user experience and preference. We conducted a lab study to compare interaction in a photo-sorting task using gesture only, or the combination of g...

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipe...

The International Mouse Phenotyping Consortium (IMPC) is providing the world's first functional catalogue of a mammalian genome by characterising a knockout mouse strain for every gene. A robust and highly structured informatics platform has been developed to systematically collate, analyse and disseminate the data produced by the IMPC. As the firs...

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipe...

The Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were developed to address the lack of reproducibility in biomedical animal studies and improve the communication of research findings. While intended to guide the preparation of peer-reviewed manuscripts, the principles of transparent reporting are also fundamental for in viv...

The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model...

10.1093/nar/gku1193 INFRAFRONTIER––providing mutant mouse resources as research tools for the international scientific community INFRAFRONTIER Consortium *, ABSTRACT The laboratory mouse is a key model organism to in-vestigate mechanism and therapeutics of human dis-ease. The number of targeted genetic mouse models of disease is growing rapidly due...

Image labeling with global parameters is described. In an embodiment a pose estimation system executes automatic body part labeling. For example, the system may compute joint recognition or body part segmentation for a gaming application. In another example, the system may compute organ labels for a medical imaging application. In an example, at le...

Methods of image segmentation using reduced foreground training data are described. In an embodiment, the foreground and background training data for use in segmentation of an image is determined by optimization of a modified energy function. The modified energy function is the energy function used in image segmentation with an additional term comp...

Methods of updating image segmentation following user input are described. In an embodiment, the properties used in computing the different portions of the image are updated as a result of one or more user inputs. Image elements which have been identified by a user input are given more weight when updating the properties than other image elements w...

We describe two new approaches to human pose estimation. Both can quickly and accurately predict the 3D positions of body joints from a single depth image without using any temporal information. The key to both approaches is the use of a large, realistic, and highly varied synthetic set of training images. This allows us to learn models that are la...

The International Mouse Phenotyping Consortium (IMPC) web portal (http://www.mousephenotype.org) provides the biomedical community with a unified point of access to mutant mice and rich collection of related emerging and existing mouse phenotype data. IMPC mouse clinics worldwide follow rigorous highly structured and standardized protocols for the...

A method of labeling pixels in an image is described where the pixel label is selected from a set of three or more labels. The pixel labeling problem is reduced to a sequence of binary optimizations by representing the label value for each pixel as a binary word and then optimizing the value of each bit within the word, starting with the most signi...

The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as The International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely u...

Image segmentation using star-convexity constraints is described. In an example, user input specifies positions of one or more star centers in a foreground to be segmented from a background of an image. In embodiments, an energy function is used to express the problem of segmenting the image and that energy function incorporates a star-convexity co...

Efficient global optimization techniques such as graph cut exist for energies corresponding to binary image segmentation from low-level cues. However, introducing a high-level prior such as a shape prior or a color-distribution prior into the segmentation process typically results in an energy that is much harder to optimize. The main contribution...

BioMart Central Portal is a first of its kind, community-driven effort to provide unified access to dozens of biological databases spanning genomics, proteomics, model organisms, cancer data, ontology information and more. Anybody can contribute an independently maintained resource to the Central Portal, allowing it to be exposed to and shared with...

We propose a new method to quickly and accurately predict human pose---the 3D positions of body joints---from a single depth image, without depending on information from preceding frames. Our approach is strongly rooted in current object recognition strategies. By designing an intermediate representation in terms of body parts, the difficult pose e...

This report summarizes the proceedings of the second workshop of the 'Minimum Information for Biological and Biomedical Investigations' (MIBBI) consortium held on Dec 1-2, 2010 in Rüdesheim, Germany through the sponsorship of the Beilstein-Institute. MIBBI is an umbrella organization uniting communities developing Minimum Information (MI) checklist...

The efficient application of graph cuts to Markov Random Fields (MRFs) with multiple discrete or continuous labels remains an open question. In this paper, we demonstrate one possible way of achieving this by using graph cuts to combine pairs of suboptimal labelings or solutions. We call this combination process the fusion move. By employing recent...

In this paper we introduce a new shape constraint for interactive image segmentation. It is an extension of Vek- sler's (25) star-convexity prior, in two ways: from a single star to multiple stars and from Euclidean rays to Geodesic paths. Global minima of the energy function are ob- tained subject to these new constraints. We also introduce Geodes...

The recent explosion of biological data and the concomitant proliferation of distributed databases make it challenging for biologists and bioinformaticians to discover the best data resources for their needs, and the most efficient way to access and use them. Despite a rapid acceleration in uptake of syntactic and semantic standards for interoperab...

The broad aim of biomedical science in the postgenomic era is to link genomic and phenotype information to allow deeper understanding of the processes leading from genomic changes to altered phenotype and disease. The EuroPhenome project (http://www.EuroPhenome.org) is a compre-hensive resource for raw and annotated high-throughput phenotyping data...

The broad aim of biomedical science in the postgenomic era is to link genomic and phenotype information to allow deeper understanding of the processes leading from genomic changes to altered phenotype and disease. The EuroPhenome project (http://www.EuroPhenome.org) is a comprehensive resource for raw and annotated high-throughput phenotyping data...

The MouseBook (http://www.mousebook.org) databases and web portal provide access to information about mutant mouse lines held as live or cryopreserved stocks at MRC Harwell. The MouseBook portal integrates curated information from the MRC Harwell stock resource, and other Harwell databases, with information from external data resources to provide v...

A new algorithm is presented for the automatic segmentation and classification of brain tissue from 3D MR scans. It uses discriminative Random Decision Forest classification and takes into account partial volume effects. This is combined with correction of intensities for the MR bias field, in conjunction with a learned model of spatial context, to...

Efficient and accurate fitting of active appearance models (AAM) is a key requirement for many applications. The most efficient fitting algorithm today is inverse compositional image alignment (ICIA). While ICIA is extremely fast, it is also known to have a small convergence radius. Convergence is especially bad when training and testing images dif...

Fast semi-automatic segmentation of the myocardium in 3D echocardiograms may be useful for diagnosis of heart diseases, by facilitating quantification of wall thickening and local wall motion. Segmentation in ultrasound is challenging, especially 3D myocardial segmentation, due to low signal-to-noise ratio, different tissues having a similar appear...

Automatic delineation of the myocardium in real-time 3D echocardiography may be used to aid the diagnosis of heart problems such as ischaemia, by enabling quantification of wall thickening and wall motion abnormalities. Distinguishing between myocardial and non- myocardial tissue is, however, difficult due to low signal-to-noise ratio as well as th...

Large-scale international projects are underway to generate collections of knockout mouse mutants and subsequently to perform high throughput phenotype assessments, raising new challenges for computational researchers due to the complexity and scale of the phenotype data. Phenotypes can be described using ontologies in two differing methodologies....

This paper presents GeoS, a new algorithm for the efficient segmentation of n-dimensional image and video data. The segmentation problem is cast as approximate energy minimization in a conditional random field. A new, parallel filtering operator built upon efficient geodesic distance computation is used to propose a set of spatially smooth, contras...

Efficient global optimization techniques such as graph cut exist for energies corresponding to binary image segmentation from low-level cues. However, introducing a high-level prior such as a shape prior or a color-distribution prior into the segmentation process typically results in an energy that is much harder to optimize. The main contribution...

Psychophysical studies [9], [17] show that we can recognize objects using fragments of outline contour alone. This paper proposes a new automatic visual recognition system based only on local contour features, capable of localizing objects in space and scale. The system first builds a class-specific codebook of local fragments of contour using a no...

Computational color constancy is the task of estimating the true reflectances of visible surfaces in an image. In this paper we follow a line of research that assumes uniform illumination of a scene, and that the principal step in estimating reflectances is the estimation of the scene illuminant. We review recent approaches to illuminant estimation...

EuroPhenome (http://www.europhenome.org) and EMPReSS (http://empress.har.mrc.ac.uk/) form an integrated resource to provide access to data and procedures for mouse phenotyping. EMPReSS describes 96 Standard Operating Procedures for mouse phenotyping. EuroPhenome contains data resulting from carrying out EMPReSS protocols on four inbred laboratory m...