Molecular genetics in silico

Molecular genetics in silico

Molecular geneticsin silica Fmnmi &TFBNAYIONAL ComERENa As the name suggests,lntelligeni Systems in Molecular Biology (i?&lB) began as a conference th...

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Molecular geneticsin silica Fmnmi &TFBNAYIONAL ComERENa As the name suggests,lntelligeni Systems in Molecular Biology (i?&lB) began as a conference that brought together anificial intelligence researchersinterested in molecular biologyproblems. ISMB has evolved beyond these origins and become one of the [email protected] conferencesin the young field of computationalmolecular biology. Four keynote addresses highlighted some major interests in the field. Chris Sander @uopean BioinfonnaticsInst., UK) declared this the ‘age of the genome’. Sander desctihed efforts to predict functions for large sets of protein sequences inferred from complere genomes. David Haussler (UC Santa CNZ, USA) talked about hidden IMarkov models Q-iMMs), a model framework from the speech recogmuon held that has become imponant in many computationalbiology applications. RobertWarerston(Washington Univ., USA) gave an overview of the systematic .sequencingof the 100 Mb Cuenor/~&&.r elegans genome. emphasizing the critical role of ‘production’hioinformatia in mana.ging a large genome center. Russell Doolitde (UC San Diego, USA) described how he hasused protein sequence analysis to date the lastcommon ancestor of cellular lie to a mere two billion years ago, raising the possibility that the ancient micro fossil record is not from eubacteria or archaehactena.

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The 24 talks and 71 posterscovered far more issues than I can summarize fairly here. One area showing good progresswas gene finding - de nowgene identification and exon-intmn prediction. This is timely indeed, finding genes in human sequence is notoriously diicult and systematic human genome sequencing commenced this year. Ying Xu (Oak Ridge Nationai laboratory, USA) described improvements to the GFrAH. system for eukatyotic gene findiig. Steven Sal&erg (Johns Hopkins, USA) and David Kulp (UC SantaCruz, USA) described two new gene finding methods. Kulp’s impressivework was one of the best illustrations of the advantages of full probabilistic modeling with HMMs. James Mclninch and William Hayes (Georgia Tech, USA) described recent improvements in GeneMark, a fifth-order Markov model for prokaryotic gene fmding, and Tetsushi Yada (lapanese Information Center of Scienceand Technology, USA) describeda similar but HMM-based approach that he has applied to the recently completed .S~*lechocyslis cyanohacterialgenome. The multimedia wizardry of the new Washington University Newman Center main lecture hall was bewildering at times, but it made possible nine live demos of software and World Wide Web applications. In a particularly impressive one, Gregg Hclt (UC Berkeley, USA) showed

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how Sun’sJava technology can overcome the Web’s shortcomingsas a genome data presentation tool. Webaccessible databases and efiicient presentation of vast quantities of data were major issues throughout the meeting. According to a recent anonymous review I saw,‘developmentof new generations of algorithms... is toot development nther than fundamental science’ (a quote now posted in my laboratory as our antimotto). The software-building role of computational biology in support of wetware biologists dominated ISMB ‘96, hut some participants (exemplified by the Sander and Doolittle keynote addresses) were interested in difficult and fundamental questinnsthat are best asked in si!ice. As the field maturesfrom its origins in artificial intelligence and diverse other fields, new researchproblems in molecular genetics will be an imponant component of ISMB conferencesto come - including, one hopes, next summer’s ISMB ‘97 in Greece.

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GENOM~C RESWNSES, SKAMANIALODGE, SIWENSON
Inducible genomic responses is a broad the meeting and seeded inter-disciplinary Molecular chaperones, cffectors of the theme for a conference, bringing together collaborations that will surely contribute stress response, are co-operative and many differentareasof research. By assem- towards the longer-term aim of the human ytosolic chaperones HSP90, bling a diverse grruf: of Investigaromthe oig~.nizc-rs. HGP70and HDJl each have distinct roles in confetence co-chairpersons(William Heck. One theme ‘xas synergy. The cellullular the recognitinn and mf61ding of a nonL‘?, illinois, U.S.\; John Hickman. Un:.. response to various typos d stress renative protein. In prokatyotic cells, the ht;ncDes:er. I&: ,nd Richard ?-lcnmoto, vealed some remarkable and unexpected DnaK and DnaJ chaperones function synNsnh~rslem Univ.. USA) aimed ‘to examples of synergy. Using yeast contain- ergistically to prevent aggregation or to increase understanding of molecular and ing the human oestrogen receptor, John disaggregdte protein substrates (Costa cellular stress-inducibleresponses with a Mciachlan (Tulane Univ., USA) showed Georgopolous,Univ. Geneva, Switzerland). view to applyingthis information to human how two pesticides, each with weak Disaggregation can lead to apparent actidiseases, especially neoplastic diseases’. oestrogenic activity, were 1000 times more vation of a substrate, probably due to Topics included: cellular responses potent when administered together. Such release from physicalconstraintrather than induced by UV, oxiciative stressand DNA synergisticaction of environmentalchemi- biochemical activation.Interaction of DnaJ damage; the detection and response t6 cals could explain the feminizationof fish with DnaK is dependent upon the aminoheavy metals and drugs; the heat shock in UK estuaries, and may have wideterminal 1’ domain and J domains have response;monitoringof genomic integrity; spread impact on sex determinationduring now been found in other proteins, includmechanismsof cytotoxic drug resistance; development. ing SV40 large T antigen, indicating an and proteasome-mediated protein degraDiverse chemical and physiological extended family of functionally related dation From this broad spectrum of topics stressesoperate synergistically16 activate proteins. a number of unifying themes emerged, the stressresponse via heat shock factor 1 in the course of the meeting it became which enhanced the undoubted successof (HSFl). as described by RichardMorimoto. apparent that RNA can play unexpected TIG SEP+EMBER1996 VOL. 12 No. 9

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