Papers by David Parry-Smith
Additional file 8: Table S7. CRISPR-Cas9 raw counts for three different organoids derived from ca... more Additional file 8: Table S7. CRISPR-Cas9 raw counts for three different organoids derived from cancer samples.
Additional file 4: Table S3. Genome-wide minimal human CRISPR-Cas9 library, MinlibCas9.
Additional file 6: Table S5. Raw counts of the CRISPR-Cas9 screens at different guide coverage pe... more Additional file 6: Table S5. Raw counts of the CRISPR-Cas9 screens at different guide coverage performed in KM-12 cancer cell line.
Additional file 7: Table S6. sgRNA counts of the CRISPR-Cas9 screens followed by drug treatment w... more Additional file 7: Table S6. sgRNA counts of the CRISPR-Cas9 screens followed by drug treatment with dabrafenib in HT-29 cells.
Additional file 5: Table S4. KS scores estimated for sgRNAs of Project Score and Avana libraries.
Additional file 3: Table S2. Reference CRISPR-Cas9 library containing sgRNAs originating from mul... more Additional file 3: Table S2. Reference CRISPR-Cas9 library containing sgRNAs originating from multiple libraries with standardised genomic annotation and guide efficiency metrics.
Additional file 9: Table S8. MinLibCas9 raw counts for three technical replicates of HT-29.
Additional file 2: Table S1. Median number of sgRNAs per gene and library size of currently avail... more Additional file 2: Table S1. Median number of sgRNAs per gene and library size of currently available human genome-wide CRISPR-Cas9 libraries.
Additional file 10: Table S9. Oligonucleotide and primer sequences.
Bioinformatics, 1991
A novel interactive method for generating multiple protein sequence alignments is described. The ... more A novel interactive method for generating multiple protein sequence alignments is described. The program has no internal limit to the number or length of sequences it can handle and is designed for use with DEC VAX processors running the VMS operating system. The approach used is essentially one of manual sequence manipulation, aided by built-in symbolic displays of identities and similarities, and strict and 'fuzzy' (ambiguous) pattern-matching facilities. Additional flexibility is provided by means of an interface to a publicly available automatic alignment system and to a comprehensive sequence analysis package.
Birkhäuser Basel eBooks, 1998
The ability to discover new lead compounds for novel therapeutic targets is a pivotal step in dru... more The ability to discover new lead compounds for novel therapeutic targets is a pivotal step in drug discovery programmes. High-throughput screening (HTS) utilises a number of platforms for the rapid screening of novel targets to accelerate this process. Key issues in HTS include assay configuration and the ability of a high-throughput screen to predict drug-target interactions accurately. This review highlights a number of issues in the HTS process and describes three key target areas that are likely to be sources of novel, therapeutically important drugs. Particular emphasis is placed on the mechanistic basis of drug-target interactions that are of prime importance in the design of HTS approaches. Critical aspects of information management related to HTS are summarised.
Bioinformatics, May 14, 2015
The rapid development of CRISPR-Cas9 mediated genome editing techniques has given rise to a numbe... more 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. Here we describe the Wellcome Trust Sanger Institute Genome Editing database (WGE), which 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 precalculated 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 highquality 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.
Burger's Medicinal Chemistry and Drug Discovery, Jan 15, 2003
Bioinformatics is the science of understanding the organization of information in biological syst... more Bioinformatics is the science of understanding the organization of information in biological systems and exploiting that understanding in solving biological problems. Such problems typically involve assessment of the function of a gene by comparing its similarity with that of previously characterized genes or gene products. In the context of drug discovery, bioinformatics is used both as a means of enabling identification of novel drug targets and also of organizing data in drug discovery information systems. An understanding of the relationships between data, information, and knowledge in these research processes is crucial to appreciating the impact bioinformatics can make in drug discovery. Aspects of some of the bioinformatics necessary to gain an insight into the use of genomics are presented, along with discussions of transcript expression profiling, functional genomics, and structural genomics as sources of data for bioinformatics. Keywords: bioinformatics; transcript profiling; functional genomics; information management; knowledge management; target discovery; structural genomics; sequence analysis; expressed sequence tags
Springer eBooks, 1995
Studies of the structures and amino-acid sequences of proteins, and the relationships between str... more Studies of the structures and amino-acid sequences of proteins, and the relationships between structure and function, are increasing rapidly in terms of the quantity of information available, the number of groups engaged in the field and the areas in which the resultant knowledge is being applied. An obvious impetus results from the projects to determine the entire genetic constitution of humans and other species, which demands interpretation in terms of the proteins which the chromosomal nucleic acid encodes. Many such proteins have been characterised solely as the translations of open reading frames of the nucleic acid code and are likely to be of unknown function and 3-dimensional structure. It seems clear, however, that protein molecules and their constituent domains belong to families that have evolved from a common ancestor and that there may well only be between one and two thousand such families. This number should be compared to the number of proteins for which sequences are so far known (over 80000 in the current release of the OWL composite, non-redundant database (Akrigg et a1..1992; Bleasby & Wootton, 1990) and the 500 or so different proteins whose 3-dimensional structures are known.
PubMed, Sep 1, 1994
PRINTS is a compendium of protein motif 'fingerprints'. A fingerprint is defined as a group of mo... more PRINTS is a compendium of protein motif 'fingerprints'. A fingerprint is defined as a group of motifs excised from conserved regions of a sequence alignment, whose diagnostic power or potency is refined by iterative databasescanning (in this case the OWL composite sequence database). Generally, the motifs do not overlap, but are separated along a sequence, though they may be contiguous in 3D-space. The use of groups of independent, linearly- or spatially-distinct motifs allows protein folds and functionalities to be characterised more flexibly and powerfully than conventional single-component patterns or regular expressions. The current version of the database contains 200 entries (encoding 950 motifs), covering a wide range of globular and membrane proteins, modular polypeptides, and so on. The growth of the databaseis influenced by a number of factors; e.g. the use of multiple motifs; the maximisation of sequence information through iterative database scanning; and the fact that the database searched is a large composite. The information contained within PRINTS is distinct from, but complementary to the consensus expressions stored in the widely-used PROSITE dictionary of patterns.
PubMed, 1995
We have cloned cDNAs encoding three human alpha-1 adrenergic receptor (AR) subtypes and character... more We have cloned cDNAs encoding three human alpha-1 adrenergic receptor (AR) subtypes and characterized pharmacological properties of the expressed receptor protein. A number of significant sequence corrections have been identified and compared with previously published data, at both nucleotide and amino acid levels; the most major differences occur for the human alpha-1a/dAR. Pharmacological characterization was performed simultaneously using six cloned alpha-1AR subtypes (human and rat alpha-1a/d, human and hamster alpha-1b, human and bovine alpha-1c) stably expressed in rat-1 fibroblasts at approximately equal receptor concentrations (1-2 pmol/mg of total protein). In general, human alpha-1AR subtypes have similar pharmacology compared to their rat, hamster and bovine homologs, although a few minor species differences important for alpha-1AR classification are noted. In addition, much lower inactivation (approximately 20%) by the alkylating agent chloroethylclonidine is noted in this study compared to previous reports for both human and bovine alpha-1cAR membrane preparations. All six alpha-1AR subtypes couple to phosphoinositide hydrolysis in a pertussis toxin-insensitive manner, including the cloned human alpha-1a/dAR which had not been expressed previously. In spite of significant sequence differences between human alpha-1ARs and their other species counterparts, previously established ligand selectivity remains fairly comparable. In summary, these data represent the first side-by-side comparison of pharmacological properties between species homologs of alpha-1AR subtypes and should facilitate the development of alpha-1AR subtype selective drugs for clinical use.
Biochemical Education, Oct 1, 1992
This is the third volume of personal recollections. They include: Physics and the riddle of life,... more This is the third volume of personal recollections. They include: Physics and the riddle of life, by Max Perutz; an octogenarian looks back, by Albert Neuberger; Wladimir Englehardt, the man and the scientist; autobiographical notes from a nomadic biochemist, by Herman Kalckar; enzymic regulation, by Albert0 Sols; Jean Brachet's life; my love affair with membranes, by Aser Rothstein; never a dull moment, by Henryk Eisenberg and total synthesis of insulin by Chen-Lu Tsou. These very interesting accounts put the flesh onto the biochemical skeleton and make it live (and dance).
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Papers by David Parry-Smith