U.s., Russian Collaborators Devise Near-perfect Method To Identify Genes Across Species Lines

A new method can find a human gene if an analogous gene from any other life form is already known.

While other techniques already exist to find cross-species gene analogs, this method is far more accurate. So the new method – devised through the collaborative efforts of U.S. and Russian researchers working at the University of Southern California – is likely to find ready applications in biotechnology, evolutionary biology and medical research.

The researchers, two in Russia and one in the United States, describe the method in the Aug. 20 issue of the Proceedings of the National Academy of Science.

“Hunting for human genes is a massive, painstaking undertaking that typically takes years and costs tens or even hundreds of millions of dollars,” says co-author Pavel A. Pevzner, Ph.D., a professor of mathematics and computer science at USC. “With this method, we can find a human gene if an analogous gene from another species has been identified. The species doesn’t matter: mouse, chicken, frog. Anything alive can serve as a template to find human genes.”

Many cancer-causing genes already identified in mice and other laboratory animals are thought to have analogs that cause cancer in humans. “All of this animal research can now be translated far more quickly into human gene sequences, and ultimately, we hope, into treatments and cures.”

Pevzner and his Russian collaborators – Mikhail S. Gelfand, Ph.D., of the Institute of Protein Research at the Russian Academy, and Andrey A. Mironov, Ph.D., of the Laboratory of Mathematical Methods at the Russian National Center for Biotechnology – have devised a method that overcomes formidable obstacles.

In very simple life forms, such as bacteria, genes are written into the organism’s hereditary material as continuous strings of information, recording genetic information in the four-letter base-pair AGCT alphabet of DNA.

In man and other vertebrates, the situation is much less straightforward, even though exactly the same alphabet of letters is used. A human gene, consisting of a message roughly 2,000 letters long, is typically broken into submessages called “exons.” These exons are shuffled, seemingly at random, into a section of chromosomal DNA as many as a million letters long.

A typical human or mammalian gene can have 10 exons or more. Recently, scientists reported a gene written in 54 separate exons. Another, linked to breast cancer, has 27.

“This situation is comparable to a magazine article that begins on page one, continues on page 13, then takes up again on pages 43, 51, 53, 59, 70, 74, 80 and 91, with pages of advertising and other articles appearing in between,” Pevzner explains. “We don’t understand why these jumps occur or what purpose they serve. Thankfully, like a magazine, the exons stay in order. They don’t jump backward. You always read in the same direction.”

The jumps are inconsistent from species to species. An “article” in an insect edition of the genetic magazine will be printed differently than the same article appearing in a worm edition. “The pagination will be completely different,” Pevzner explains, “and it will not be consistent: the information that appears on a single page in the human edition may be broken up into two in the wheat version, or vice versa.”

The USC scientist continues, noting yet another complication: “The genes themselves, while related, are quite different. The mouse-edition gene is written in mouse language; the human-edition gene in human language. It’s a little like German and English, which are related languages: many words are identical or similar, but many others are not. Nevertheless, to find the analogous genes, we must be able to recognize these differently spelled words written on different pages as the same message.”

Even there, the complications do not end. If it were just a matter of picking out a known “magazine story,” whether in mouse-DNA language or human-DNA language, from intervening material that was obviously advertising, the problem would be far less difficult. Perversely, the “advertising” can mimic the message. Long sequences of “junk DNA,” as it’s sometimes called, may be identical to parts of the message but not be part of the gene. Such sequences are meant to be skipped when the message is read.

Earlier methods for deciding what is advertising and what is story depended on statistics. To continue the magazine analogy, “it is something like going through back issues of the magazine and finding that human-gene ‘stories’ are less like to contain phrases like ‘For Sale,’ telephone numbers, and the dollar sign,” Dr. Gelfand explains.

While better than random reconstruction, these statistical methods are inaccurate at best.

The method developed by Pevzner and his colleagues zeros in on the proper “pages” by making first a list of all pages that are potentially part of the “story” – all pages that seem to have sequences that are part of the message.

The software developed by the three researchers then automatically combines and recombines these pages into the set that makes the best fit. The method works best when a “target protein” is available to guide the search. All the stories in the genetic magazine are recipes for making proteins. If you have the protein, you know the way the recipe reads (though you don’t know where to find it in the maze of advertising).

The method’s accuracy with such guidance is always good, the scientists report, and often remarkable – 99% or 100% accurate.

The Proceedings paper contains a listing of trials of the method on nearly 100 different genes, 47 of them from mammals (mostly mice), 45 from other organisms, including bacteria.

For mammals, 40 of 47 reconstructions were perfect – 100% accurate. In six of the remaining cases, where the method did not give a perfect prediction, it came close, accurately predicting 94-97%.

Even the lone case in which the method seemed to fall down – predicting with 75% accuracy on the basis of mouse data – the failure was interesting. In this case, chicken data for the same gene were also available to use for predictions, and the prediction of the human gene from the chicken data was 100% accurate. “This is surprising, given that we think of humans as more closely related to mice than to chickens,” Pevzner notes.

Even when the starting point of the reconstruction was target material from organisms evolutionarily extremely different from humans – bacteria, yeasts and others – 25 of the reconstructions were 100% accurate.

“We believe our method will prove extremely useful to researchers, not just in biotechnology, but also evolutionary biology,” Pevzner says. “It will enable biologists to trace, with exceptional precision, exact degrees of difference between gene organization in different species. And it will help, we think, to establish evolutionary relationships between species.”

Ismb-95 Addresses Computational Issues

Some 270 delegates attended the Third International Conference on Intelligent Systems for Molecular Biology (ISMB-95) held in Cambridge, England, on July 16-19, 1995. The conference brought together scientists who are using advanced computational methods to address problems in molecular biology. These methods include data modeling, machine learning, artificial intelligence, cognitive science, robotics, combinatorial and stochastic optimization, adaptive computing, string and graph algorithms, linguistic methods, and parallel computer technologies.

The conference was preceded by 8 introductory and advanced tutorials attended by 187 delegates. The best-attended tutorials were (1) Protein Structure Prediction and (2) Statistical Foundations of Multiple Sequence Alignments and Structure Prediction.

The conference consisted of 8 sessions and 26 oral papers on key bioinformatics issues: protein structure and docking, sequence alignment, protein sequence and structure, understanding sequence function, RNA sequence and structure, genome information systems, gene finding and gene structure, and database searching. Topics of particular interest included methods for automatically identifying different structural and functional domains within protein structures and the use of advanced statistical methods (e.g., hidden Markov models and stochastic context-free grammars) for identifying complex protein sequence patterns and sequence relationships. Recurring themes were (1) genome-information integration and presentation and (2) methods for rapidly searching DNA and protein sequence and structure databases for related molecules.

Throughout the meeting, two general trends could be discerned: (1) the need to compare new approaches to existing methods, with the associated complexities of selecting appropriate data sets, and (2) the desire to make predictions of biological function that could be validated properly. This raises the general question of how to represent biological function in molecular biology databases. More complete databases of biological processes and pathways that can be linked to sequence and structure data sets are clearly needed.

A new topic was the search for efficient and accurate methods of finding the best fit between macromolecular structures (docking), with both protein-protein and protein-ligand interactions being considered. Several papers and a tutorial covered the challenges of protein structure prediction and the refinements to methods for threading sequences through known protein structures. Applications for machine-learning methods (e.g., neural networks, hidden Markov models, and genetic algorithms) were well represented, and a new approach based on a simulation of the immune system was presented. RNA structure prediction was addressed by several different techniques, including the use of linguistics and graph theory.

Conference proceedings (ISBN 0-929280-83-0), including 26 oral papers and 22 posters featured in the formal poster session, can be obtained directly from AAAI/MIT Press (info@). Proceedings of ISMB-93 (ISBN 0-929280-47-4) and ISMB-94 (ISBN 0-929280-68-7) are also available from AAAI. ISMB-96, being organized by David States, will be held June 12-15 at Washington University, St. Louis.

Aliens A Big Concern

People usually believe in a whole variety of things because it delivers them some sort of feeling of personality or ease and comfort.

Is there lifestyle out there? Are we alone? How did we get here?

These are the big concerns. For what it is value, I believe there are big hits developing history. The essentially unique effect from each big beat would generate many galaxies (I know, a contradiction in terms). The only popular element would be that each began from a rush of power. In our situation, some of that power was changed to topic, and we are the effect. Definitely there is no explanation why the power could not have been become another sensation that our expressions and our perspective cannot recognize. This may perhaps be a kind that is way off the range of our electro-magnetic array, or using a different array permanently.

Should such galaxies are available we could not view them as our feelings and devices are updated to our own whole world and not to an unfamiliar one. An example of the issue of creating the living of these aliens is this: what if the aliens did not have the element of place in their instrument kit? In other phrases they didn’t are available as bodily organizations at all? You may question therefore that perhaps they are designed up of protons, or power waves? No, even these phenomena would take up some place, and my aliens have no place in which to provide anything. Of course it is difficult to explain how they would are available, but perhaps an example would be the best element. Just think about imagined and, for a small, please overlook that imagined ocean themselves take up place. Perhaps our aliens are merely designed up of opinions or thoughts that take around us but have no bodily kind or a bodily house. These opinions will merely are available around us. The issue is that I have already run into issue with expressions. The phrase “around” advises place and as I said previously, a imagined in our whole world requires up some place. You see, aliens probably are available, but we cannot history them nor, with the disadvantages of our expressions, we cannot explain them. A great example of decreasing into the entice of our own expressions is the phrase “Aliens from external space”. The example I available would not operate, as the phrases “from”, “outer” and “space” would not apply! As we are restricted by expressions, all we have is our thoughts.

Top Tricks to Invest in an Astronomy Telescope

The choice of astronomy telescopes depends upon the time you will devote to the observation, which site you have access to, the ease of use and control and, as always, your budget. Some positive aspects and negatives for some different astronomy telescope are discussed here depending upon their designs.

1. A refracting astronomical telescope makes use of two lenses. The lens in the front of the telescope, called the objective lens, produces an upside-down image of the object. The lens near the eye, called the eye lens, acts as an ordinary magnifying glass to magnify that upside-down image. Naturally, each of these two elements of the telescope could be made up of several lenses, to combat certain inherent limitations, or aberrations.

Advantages

Standard-quality achromatic or apochromatic refractors have some advantages over other telescope designs. Firstly, refractors, by default, bear a entirely clear aperture. There is no central obstruction that leads light to be distributed from brighter to darker areas. So, the visitor can experience a better contrast in refractors. In these telescopes refractors often are adduced as the premier instruments for a planetary and double star observation.

Low maintenance is the second advantage of refractors as lenses do not need recoating like mirrors do. Furthermore, the optical tube assembly of a refractor generally does not depend upon collimation. Lens is placed into the tube and usually does not get misaligned, unless it is dag up to some major trauma.

Disadvantages

As the refractor is a closed-tube assembly, it may demand a extended amount of time to cool to ambient temperature. Presently used thin-walled aluminum tubes have decreased this period significantly, but cool-down time still should be accept into account.

2. Newtonian reflecting telescopes consists of two mirrors – a large primary mirror at the bottom of the tube and a small, flat secondary mirror near the top of the tube. Front- lights arrive into the tube, fall on the primary mirror, get reflected to the secondary mirror, and then it is mirrored again into the eyepiece.

Advantages

These reflecting telescopes does not ached any chromatic aberration. Included mirrors bear only one optical surface, whereas an apochromatic lens has between four and eight causing it less expensive to develop.

Disadvantages

Secondary mirror forms what is named a “central obstruction” which results in unnatural distribution of light and loss of contrast in the image. In case to resolve this problem, a few manufacturers have prepared so- called planetary Newtonians, having smaller central obstructions (some as small as 16% of the aperture).

Important things to keep in mind when investing a telescope :

a. Know everything you can about telescopes for instance manufacturers’ ads, catalogs, and especially read telescope reviews with customer score on a particular product. The Astronomy magazine will be a useful resource for both advertise and telescope reviews.

b. If a telescope is included with low- quality, high- power eyepiece, high (albeit empty) magnifications can be attained. So, it is meaningless to claim 500x magnification for telescopes. To make change of the magnification of a telescope, you need to change the eyepiece.

c. If you are serious about buying a telescope, consult with your nearest astronomy club where you can get all the assistance on understanding all feature of a particular.

d. General review says that the bigger the telescope, the better to get view. But, if you need often use of it, then choose smaller one as it is easy to set up a small refractor on a standard tripod rather than a large Newtonian reflector on a heavy mount.

And finally, always remember: a telescope is a useful tool- but only if you know what to perform with it !

Preventing Viruses

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