News

Gut bacteria

Photo by David Gregory and Debbie Marshall, Wellcome Images. 

Recent deep sequencing studies are providing an increasingly detailed picture of the genetic composition of the human microbiome, the diverse collection of bacterial species that inhabit the gut. At the same time, however, little is known about the dynamics of these colonies, particularly why certain microbial strains outcompete others in the same environment. In a new paper published in the journal Molecular Systems Biology, Department of Systems Biology Assistant Professor Harris Wang, in collaboration with Georg Gerber and researchers at Harvard University, report on their development of the first method for using functional metagenomics to identify genes within commensal bacterial genomes that give them an evolutionary fitness advantage.

Bacterial evolutionary relationships

Image courtesy of Germán Plata and Dennis Vitkup.

Columbia News has just published an article covering recent research by associate professor Dennis Vitkup and postdoctoral research scientist Germán Plata that uses simulations of bacterial metabolism as a lens for studying how phenotypes adapt and diversify across evolutionary time scales. The article reports:

Despite their omnipresence, microbial evolutionary adaptations are often challenging to study, partly due to the difficulty of growing diverse bacteria in the lab. “Probably less than a dozen bacteria are really well studied in the laboratory,” Vitkup says.

Writing in the journal Nature this past January, Vitkup and Plata applied computational tools to investigate bacterial evolutionary adaptations by simulating metabolism for more than 300 bacterial species, covering the entire microbial tree of life.

Andrea Califano and Aris Floratos
Andrea Califano and Aris Floratos will lead an effort to reclassify tumors catalogued in TCGA according to their master regulators.

Andrea Califano and Aris Floratos, faculty members in the Columbia University Department of Systems Biology, have received a two-year, $624,236 subcontract to develop a new classification system of cancer subtypes. The agreement was awarded through a subcontract from Leidos Biomedical Research, Inc., which operates the Frederick National Laboratory for Cancer Research for the federal government.  

By performing an integrative analysis of genomic data from the Cancer Genome Atlas (TCGA) and proteomic data from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), the researchers plan to recategorize tumors collected in TCGA based on the master regulator genes that determine their state. This is in contrast to other approaches based on expression of genes that reflect tissue lineage and proliferative processes. In addition, the team will link the genetics of each tumor sample to the specific master regulators that determine its state using a recently published novel algorithm (DIGGIT). Ultimately, the project aims to provide a more useful catalog of pan-cancer subtypes that could help to identify biomarkers and therapeutic targets for specific kinds of tumors, and ultimately provide a resource to guide the next generation of precision medicine.

“We have to reevaluate the way in which we organize tumors within subtypes, using both gene expression data and mutational data,” says Dr. Califano. “Right now the common approach is to classify tumor types based on rather generic genes that are differentially expressed between subtypes. But most of these genes play no role in actually driving the disease. We want to shift the emphasis and classify tumors based on the genes that truly regulate tumor state and survival.”

Harris Wang

Harris Wang, an assistant professor in the Columbia University Department of Systems Biology and Department of Pathology and Cell Biology, has been selected to receive a 2015 Alfred P. Sloan Foundation Research Fellowship in computational and evolutionary molecular biology. This two-year, $50,000 grant will support work that combines methods from synthetic biology and computational biology to study how horizontal gene transfer contributes to microbial evolution.

Since 1955, the Sloan Research Fellowship program has supported outstanding early-career scientists in recognition of their achievements and their potential to make important contribution to their fields. This year’s fellows included 126 investigators, with 12 awardees in the field of computational and evolutionary molecular biology. Other disciplines represented in the awards include chemistry, computer science, economics, mathematics, neuroscience, ocean sciences, and physics.

Autism Spectrum Disorders Genetic Network

Network of autism-associated genes. (Credit: Dennis Vitkup)

The following article is reposted with permission from the Columbia University Medical Center Newsroom. Find the original here.

People with autism have a wide range of symptoms, with no two people sharing the exact type and severity of behaviors. Now a large-scale analysis of hundreds of patients and nearly 1000 genes has started to uncover how diversity among traits can be traced to differences in patients’ genetic mutations. The study, conducted by researchers at Columbia University Medical Center, was published Dec. 22 in the journal Nature Neuroscience.

Autism researchers have identified hundreds of genes that, when mutated, likely increase the risk of developing autism spectrum disorder (ASD). Much of the variability among people with ASD is thought to stem from the diversity of underlying genetic changes, including the specific genes mutated and the severity of the mutation.

“If we can understand how different mutations lead to different features of ASD, we may be able to use patients’ genetic profiles to develop accurate diagnostic and prognostic tools and perhaps personalize treatment,” said senior author Dennis Vitkup, PhD, associate professor of systems biology and biomedical informatics at Columbia University’s College of Physicians & Surgeons.