Michael J. Morgan

Bio: Michael J. Morgan is an academic researcher from Monash University. The author has contributed to research in topics: Iterative reconstruction & Diffraction. The author has an hindex of 39, co-authored 153 publications receiving 34668 citations. Previous affiliations of Michael J. Morgan include University of California, Los Angeles & Swansea University.

Initial sequencing and analysis of the human genome.

Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

Initial sequencing and comparative analysis of the mouse genome.

Abstract: The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.

The Human Genome Project: Lessons from Large-Scale Biology

Abstract: The Human Genome Project has been the first major foray of the biological and medical research communities into “big science.” In this Viewpoint, we present some of our experiences in organizing and managing such a complicated, publicly funded, international effort. We believe that many of the lessons we learned will be applicable to future large-scale projects in biology.

The genome of the model beetle and pest Tribolium castaneum

Abstract: Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products We describe its genome sequence here This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development Systemic RNA interference in T castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control

Funding for malaria genome sequencing

Abstract: Sir — We should like to correct a statement in your Briefing on malaria about funding for the sequencing of the genome of the malaria parasite Plasmodium falciparum (Nature 386, 535–540; 1997). You report that the US Department of Defense, the US Burroughs Wellcome Fund, the UK Wellcome Trust and the US National Institutes of Health (NIH) have created a fund for this sequencing effort. In fact, no ‘fund’ has been established and there has been no pooling of funds among the donors. However, an exciting international consortium of scientists and funding agencies has been formed during the past year to provide the funds and reagents required to sequence the P. falciparum genome, and to produce, annotate and publish these sequences. We estimate that it will cost a minimum of $15 million to complete and annotate the 30-megabase P. falciparum genome. In the initial pilot phase, funding has been used to develop methods and to produce the reagents required for the high-throughput sequencing and for annotating the sequences. As a result of progress so far, the plan is to sequence the 14 chromosomes separately and to divide the work by chromosome, with about half the work being done in the United States and half in England. The work in the United States has initially been supported by grants from the NIH and the Burroughs Wellcome Fund and in England by the Wellcome Trust. Subsequent support will also be provided by the US Department of Defense. In the United States, the Naval Medical Research Institute is providing P. falciparum DNA and chromosomes, the Institute for Genomic Research will be doing a significant amount of the high-throughput sequencing and Stanford University is committed to sequencing at least one of the larger chromosomes. The donors are also supporting research on clone stability, library construction and optimization of sequencing reagents for the project at these three institutions, and at Roswell Park Cancer Institute and Harvard University. In England, the Institute of Molecular Medicine at the University of Oxford is providing P. falciparum reagents, and sequencing is being done at the Sanger Centre at Cambridge. It is expected that during the next few years a number of other laboratories may participate in the effort. The participants (scientists and donors) involved in this collaborative undertaking coordinate their activities through conference calls, e-mails and meetings. The researchers and funders met in Baltimore, Maryland, in December 1996 and will meet in Cambridge, England, on 16–17 June 1997. In addition, there has been an effort to involve the broader malaria community in this project and to facilitate widespread dissemination of the genomic information. There are substantial scientific obstacles to be overcome before the sequence of the P. falciparum genome is fully elucidated. Nonetheless, during the past year we have made great strides in identifying the funds required to pursue the project, building a strong group of scientists and institutions to execute the science, and establishing a collaborative network of scientists and donors. We believe that this project will provide a road map for malaria research in the twentyfirst century, research that will lead to improved treatment and prevention of a parasitic infection that causes hundreds of millions of illnesses, and millions of deaths annually. Stephen L. Hoffman Malaria Program, Naval Medical Research Institute, Bethesda, Maryland 20889-5607, USA e-mail: hoffmans@nmripo.nmri.nnmc.navy.mil William H. Bancroft Military Infectious Disease Research Program, US Army Medical Research and Materiel Command, Frederick, Maryland 21703, USA Michael Gottlieb Stephanie L. James Parasitology and International Programs Branch, NIAID/NIH, Bethesda, Maryland 20892, USA Enriqueta C. Bond Burroughs Wellcome Fund, Morrisville, North Carolina 27560, USA John R. Stephenson Michael J. Morgan The Wellcome Trust, London NW1 2BE, UK correspondence

The Pfam protein families database

Abstract: Pfam is a widely used database of protein families and domains. This article describes a set of major updates that we have implemented in the latest release (version 24.0). The most important change is that we now use HMMER3, the latest version of the popular profile hidden Markov model package. This software is approximately 100 times faster than HMMER2 and is more sensitive due to the routine use of the forward algorithm. The move to HMMER3 has necessitated numerous changes to Pfam that are described in detail. Pfam release 24.0 contains 11,912 families, of which a large number have been significantly updated during the past two years. Pfam is available via servers in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/).

BLAST+: architecture and applications.

Abstract: Sequence similarity searching is a very important bioinformatics task. While Basic Local Alignment Search Tool (BLAST) outperforms exact methods through its use of heuristics, the speed of the current BLAST software is suboptimal for very long queries or database sequences. There are also some shortcomings in the user-interface of the current command-line applications. We describe features and improvements of rewritten BLAST software and introduce new command-line applications. Long query sequences are broken into chunks for processing, in some cases leading to dramatically shorter run times. For long database sequences, it is possible to retrieve only the relevant parts of the sequence, reducing CPU time and memory usage for searches of short queries against databases of contigs or chromosomes. The program can now retrieve masking information for database sequences from the BLAST databases. A new modular software library can now access subject sequence data from arbitrary data sources. We introduce several new features, including strategy files that allow a user to save and reuse their favorite set of options. The strategy files can be uploaded to and downloaded from the NCBI BLAST web site. The new BLAST command-line applications, compared to the current BLAST tools, demonstrate substantial speed improvements for long queries as well as chromosome length database sequences. We have also improved the user interface of the command-line applications.

MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment

Abstract: With its theoretical basis firmly established in molecular evolutionary and population genetics, the comparative DNA and protein sequence analysis plays a central role in reconstructing the evolutionary histories of species and multigene families, estimating rates of molecular evolution, and inferring the nature and extent of selective forces shaping the evolution of genes and genomes. The scope of these investigations has now expanded greatly owing to the development of high-throughput sequencing techniques and novel statistical and computational methods. These methods require easy-to-use computer programs. One such effort has been to produce Molecular Evolutionary Genetics Analysis (MEGA) software, with its focus on facilitating the exploration and analysis of the DNA and protein sequence variation from an evolutionary perspective. Currently in its third major release, MEGA3 contains facilities for automatic and manual sequence alignment, web-based mining of databases, inference of the phylogenetic trees, estimation of evolutionary distances and testing evolutionary hypotheses. This paper provides an overview of the statistical methods, computational tools, and visual exploration modules for data input and the results obtainable in MEGA.

The sequence of the human genome.

Abstract: A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.