We will review some of the major results in random graphs and some of the more challenging open problems. We will cover algorithmic and structural questions. We will touch on newer models, including those related to the WWW.

Random graphs

BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

Background
Multiple genome alignment remains a challenging problem. Effects of recombination including rearrangement, segmental duplication, gain, and loss can create a mosaic pattern of homology even among closely related organisms.

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0011147&type=printable

progressiveMauve: Multiple Genome Alignment with Gene Gain, Loss and Rearrangement

Transcription regulation networks control the expression of genes. The transcription networks of well-studied microorganisms appear to be made up of a small set of recurring regulation patterns, called network motifs. The same network motifs have recently been found in diverse organisms from bacteria to humans, suggesting that they serve as basic building blocks of transcription networks. Here I review network motifs and their functions, with an emphasis on experimental studies. Network motifs in other biological networks are also mentioned, including signalling and neuronal networks.

/pdf/network-motifs-theory-and-experimental-approaches-40rp9yj6zc.pdf

Network motifs: theory and experimental approaches

Genes and proteins generate molecular circuitry that enables the cell to process information and respond to stimuli. A major challenge is to identify characteristic patterns in this network of interactions that may shed light on basic cellular mechanisms. Previous studies have analyzed aspects of this network, concentrating on either transcription–regulation or protein–protein interactions. Here we search for composite network motifs: characteristic network patterns consisting of both transcription–regulation and protein–protein interactions that recur significantly more often than in random networks. To this end we developed algorithms for detecting motifs in networks with two or more types of interactions and applied them to an integrated data set of protein–protein interactions and transcription regulation in Saccharomyces cerevisiae. We found a two-protein mixed-feedback loop motif, five types of three-protein motifs exhibiting coregulation and complex formation, and many motifs involving four proteins. Virtually all four-protein motifs consisted of combinations of smaller motifs. This study presents a basic framework for detecting the building blocks of networks with multiple types of interactions.

/pdf/network-motifs-in-integrated-cellular-networks-of-pkdn0ycd4r.pdf

Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction.

Motivation: Several genome-scale efforts are underway to reconstruct metabolic networks for a variety of organisms. As the resulting data accumulates, the need for analysis tools increases. A notable requirement is a pathway alignment finder that enables both the detection of conserved metabolic pathways among different species as well as divergent metabolic pathways within a species. When comparing two pathways, the tool should be powerful enough to take into account both the pathway topology as well as the nodes' labels (e.g. the enzymes they denote), and allow flexibility by matching similar---rather than identical---pathways.

Results: MetaPathwayHunter is a pathway alignment tool that, given a query pathway and a collection of pathways, finds and reports all approximate occurrences of the query in the collection, ranked by similarity and statistical significance. It is based on a novel, efficient graph matching algorithm that extends the functionality of known techniques. The program also supports a visualization interface with which the alignment of two homologous pathways can be graphically displayed.

We employed this tool to study the similarities and differences in the metabolic networks of the bacterium Escherichia coli and the yeast Saccharomyces cerevisiae, as represented in highly curated databases. We reaffirmed that most known metabolic pathways common to both the species are conserved. Furthermore, we discovered a few intriguing relationships between pathways that provide insight into the evolution of metabolic pathways. We conclude with a description of biologically meaningful meta-queries, demonstrating the power and flexibility of our new tool in the analysis of metabolic pathways.

Availability: Code and data upon request.

Contact: pinter@cs.technion.ac.il

Alignment of metabolic pathways

A computer system provides a graphical user interface (GUI) to assist a user in completing electronic forms. The computer includes components such as a processor, user interface, and video display. Using the video display, the processor presents a row entry template including a menu field and an associated data field. The user completes the menu field by selecting a desired menu entry from a list of predefined menu entries. The user completes the data field by entering data into the data field. This format is especially useful when the data entry provides data categorized by the menu entry, explains the menu entry, or otherwise pertains to the menu entry. Each time the GUI detects activation of a form expand key, it presents an additional row entry template for completion by the user. Upon selection of a submit key, data of the completed form is sent to a predefined destination, such as a linked list, table, database, or another computer. Thus, by planned selection of menu entries, the user can limit his/her completion of an electronic form to blanks applicable to that user, avoiding the others. Nonetheless, the form can be easily expanded row by row to accommodate as many different blanks as the user wishes to complete. The invention may be implemented by a host sending a remote computer machine-executable instructions which the remote computer executes to provide the GUI, where the remote computer ultimately returns the completed form data to the host.

System for directly accessing fields on electronic forms

Like plant chloroplasts, the photosynthetic membranes of marine cyanobacteria contain two photosystems: photosystem II (PSII) mediates electron transfer from water to plastoquinones and PSI mediates electron transfer from plastocyanin to ferredoxin, thereby generating reducing power needed for CO2 fixation in the form of NADPH. Core PSII genes were recently found in cyanophages, viruses that infect cyanobacteria, where they presumably supplement the host's photosynthetic abilities. Now a trawl through metagenomic data from the Sorcerer II Global Ocean Sampling Expedition and through viral biomes reveals that PSI components are also present in cyanophages, presumably also contributing to overall photosynthetic performance. Cyanobacteria are important contributors to photosynthetic productivity in the open oceans. Functional photosystem II components are known to be encoded in cyanophage genomes and are suggested to provide a fitness advantage to the virus by boosting host performance. It is now shown that photosystem I components can also be detected in cyanophages. Cyanobacteria of the Synechococcus and Prochlorococcus genera are important contributors to photosynthetic productivity in the open oceans1,2,3. Recently, core photosystem II (PSII) genes were identified in cyanophages and proposed to function in photosynthesis and in increasing viral fitness by supplementing the host production of these proteins4,5,6,7. Here we show evidence for the presence of photosystem I (PSI) genes in the genomes of viruses that infect these marine cyanobacteria, using pre-existing metagenomic data from the global ocean sampling expedition8 as well as from viral biomes9. The seven cyanobacterial core PSI genes identified in this study, psaA, B, C, D, E, K and a unique J and F fusion, form a cluster in cyanophage genomes, suggestive of selection for a distinct function in the virus life cycle. The existence of this PSI cluster was confirmed with overlapping and long polymerase chain reaction on environmental DNA from the Northern Line Islands. Potentially, the seven proteins encoded by the viral genes are sufficient to form an intact monomeric PSI complex. Projection of viral predicted peptides on the cyanobacterial PSI crystal structure10 suggested that the viral–PSI components might provide a unique way of funnelling reducing power from respiratory and other electron transfer chains to the PSI.

/pdf/photosystem-i-gene-cassettes-are-present-in-marine-virus-3z99h90s8u.pdf

Photosystem I gene cassettes are present in marine virus genomes

An “active” calendar automatically analyzes a user's calendar entries and sends machine-readable messages to destinations appropriate to content of the calendar entry. A group of event categories is established, each category specifying one class of anticipated calendar entry. An action rule database pre-associates each event category with one or more message formats each having a content and a destination. The action rule database also contains data identifying sources containing the content and destination for each message format. These sources include records of the action rule database itself, subparts of calendar entries of the pre-associated event category, one or more other databases, or a combination of the foregoing. After the calendar receives a user-submitted computer calendar entry describing a planned event, it identifies one of the event categories of the established group that classifies the planned event. For each message format pre-associated with the identified event category, the calendar determines the content and destination for the message as specified by the action rule database, and transmits the message to the destination.

Ron Y. Pinter

Papers

Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction.

Alignment of metabolic pathways

System for directly accessing fields on electronic forms

Photosystem I gene cassettes are present in marine virus genomes

Active calendar system