Integrating NGS data into clinical practice
Author Archives: Jyoti M.
One genome at a time: Mapping the cancer battlefield
Patients and families turn to genomic medicine to treat cancer
Most of us probably associate being sick with the entire body- a fever, aches, chills and other broad symptoms. When it comes to a disease like cancer, we might take an organizational step or two down to think of a specific organ or tissue: breast, lung or brain cancer.
But increasingly, patient’s stories point clearly toward a finer resolution of cancer diagnosis, down to the level of a single gene. A report in the New York Times last week describes how a team of researchers worked to identify the genetic aberration underlying a colleague’s cancer, and helped treat his leukemia with an off-label drug currently used to treat kidney cancers.
Exome sequencing pins down unusual suspects
Recent research shows clinical applications of exome sequences in diagnosing in neurodevelopmental diseases
When all four children in a single family began to develop hearing, speech and intellectual defects as infants, doctors performed routine medical and genetic tests to diagnose their condition. The tests revealed little, and the children were diagnosed with a recessive form of intellectual disability, with no apparent heritable cause. Intellectual disability, like most neurodevelopmental disorders, can be particularly tricky to identify because of the lack of precise diagnostic tests and difficulty of obtaining tissue biopsies. Researchers probing the genetics underlying such conditions recently sequenced the exomes of this family and over a hundred others with affected children, implicating several novel genes in the development of these disorders. Their research, published in Science Translational Medicine last month, also hints at ways to adopt exome sequencing in clinical practice. Read more…
Travel Grants Spring 2012 winner: Catarina Correia
And finally, a big round of applause for our first place travel grant winner, Dr. Catarina Correia! She researches protein interaction networks in autism spectrum disorders and presented her recent results at the International Meeting for Autism Research in Toronto, ON last month. We’re glad the travel grant helped her attend!
I am currently pursuing a post-doctoral project at Instituto Gulbenkian de Ciência and Instituto Nacional de Saúde Dr. Ricardo Jorge (Portugal) working on the analysis of GWAS carried out by the Autism Genome Project (AGP), a large international consortium for autism genetics. My research aims to develop a network-based approach for GWAS data analysis by combining association results with protein-protein interaction data, and characterize potentially pathogenic CNVs identified in the AGP whole genome CNV analysis. Read more…
Travel Grants Spring 2012 winner: Malay Bhattacharyya
Congratulations to our second travel grant winner! Read on to find out how he uses NextBio Research to explore oncogenic microRNAs.In Malay’s words:
I become truly amazed when I look back on my career and see how a student with undergraduate degrees in Computer Science and Electronics turned into a biology researcher. In the very first week of graduate school, I received an article on microRNAs (miRNAs), a class of short non-coding regulators of protein-coding genes, from my supervisor. Ever since that first read, I have been hooked on these endogeneous RNAs for four years and counting. Read more…
Chromatin clustering may hold cancer clues
Transcriptional regulators can change the way chromatin loops group together
Something like the image above is probably what comes to mind first when you hear ‘chromatin structure’. In reality, DNA spends only a small portion of time in these tightly coiled chromosomes. Most chromatin within cells lies in diffuse strands within nuclei. Mapping the locations of genes on these strands, scientists have found that chromatin containing more actively expressed genes tends to cluster together, as do chromatin strands containing inactive genes. Now, two recent papers show that these specific arrangements of chromatin may hold clues to developing targeted drugs for diseases like cancer. Read more…
Shedding light on genomic signatures of melanoma
A new study shows different mutation classes associated with distinct melanoma sub-types
Skin cancer remains one of the most common forms of the disease in the U.S. Though melanomas account for less than 5% of all skin cancers, they cause the large majority of deaths from the disease. Some parts of the skin (like the palms and soles) develop cancers much less frequently, and the rare ‘acral melanomas’ that originate from these types of skin have less in common with other skin cancers. Read more…
Travel Grants Spring 2012 winner: Stephanie Weldon
Here’s the first of our winning essays! Congratulations to Stephanie Weldon, one of our second place winners.
Pea aphids extracting sap (PLoS Biology, February 2010)
The inherent connectedness of biological information makes research on the web of life naturally suited to Web 2.0. I study insect-bacterium-virus symbioses, where the lateral transfer of both infectious bacteria and their virus passengers’ genetic material requires me to cross-reference very diverse data sets, a circumstance that makes NextBio’s search apps very appealing.
Maternally inherited bacterial symbionts are quite common in insects. However, research in the past decade or so has shifted from focusing on these “obligate” symbionts that are essential to a host’s survival to include ‘facultative’ symbionts that are not required for an insect to survive, but provide perks like protection from pathogenic fungi or parasites.
The divide between a facultative symbiont and a pathogen is a slim one. Since these bacteria are not obliged to squeeze into the narrow niches offered by a single tissue in one host, they can carry larger genetic baggage when they transfer between insect hosts or invade novel tissues. This allows their genomes to retain pathogenic mechanisms not always seen in obligate symbionts, and also host other mobile genetic elements like bacteriophage.
I work with pea aphids, a group of insects that have created alliances with both symbiotic bacteria (H.defensa) and their bacteriophage APSE, which collectively help the aphids resist attack by a parasitic wasp. The phage APSE carries one of several toxins that protect the pea aphid from the endoparasitic wasp by killing the wasp’s eggs; the precise mechanisms of this process are still being studied.
Bacteriophage carrying effector molecules that can influence their hosts were first studied in human pathogens. While I love working with the most diverse class of animals in the biosphere, researching insects means I lack a personal background into literature on vertebrate pathogens. One of the phage variants that I am characterizing carries a Shiga-like toxin: NextBio’s QuickView provides me immediate insights on the functions of Shiga toxins in pathogenic bacteria and their impact on gene expression in human cells.
Ranked results allow researchers to view large amounts of data without artificially limiting the potential for productive cross-fertilization from more distant sources. Another form of the APSE phage carries a homolog to the B-subunit of the cytolethal distending holotoxin. I am currently working on characterizing bacteriophage phylogenies and the phenotypic effects of mutations in the cdtB gene in this variant phage. As with the Shiga-like toxin, NextBio’s literature app provides me with easy access to information that would otherwise be time-consuming to parse. The user-friendly sentence-matching allows me to jump to the relevant portions quickly, and the inline links to informational pop-ups are also immensely handy when wading into a foreign literature. Best, though, is the tag cloud: it provides, in addition to ease of navigation, moments of unexpected serendipity when a tag suggests an avenue I never would have otherwise considered.
While I have focused primarily on data mining for projects I am running independently, in the future I hope to use NextBio to facilitate the human-interactive side of science; I am rather looking forward to finding a way to bring the genome browser into the classroom when I am teaching introductory biology in the fall. The graphical user interface makes exploring a chromosome and selecting a feature sufficiently intuitive and entertaining that a student may actually be willing to read up on features not directly related to their course work.
Heightened recognition of the importance of lateral gene transfer and symbiosis in evolution has led some scientists to suggest that the tree of life, particularly the unicellular branches, might be better depicted as a web. The combination of nested hierarchies and web-like interaction provided by NextBio makes it an unusually appropriate platform for biological research, particularly for those of us actively investigating life’s web-like qualities by delving into bacterial-eukaryotic symbioses and mobile genetic elements.
Announcing Travel Grant recipients!
Autism, entomology and microRNAs in cancer may not have much in common, but three enthusiastic researchers studying these areas are the recipients of NextBio travel grants this month: Congratulations Catarina Correia, Malay Bhattacharyya and Stephanie Weldon!
Stephanie is a graduate student in entomology at the University of Georgia, studying symbiotic interactions in insects and bacteria. We were excited to learn how she used NextBio in her studies of Shiga toxins. As she describes her research:
“I study insect-bacterium symbioses and associated mobile genetic elements, where the lateral transfer of both infectious agent and genetic material requires me to cross-reference very diverse data sets, a circumstance that makes NextBio’s search apps very appealing. Sorted results, rather than restricted results, allow researchers to quickly take in large amounts of data without artificially limiting the potential for productive cross-fertilization from more distant sources.”
Tied with Stephanie for second place is Malay Bhattacharyya, a computer scientist turned biologist at the Indian Statistical Institute. As part of his graduate research in machine intelligence, he uses in silico approaches to demonstrate the involvement of two oncogenic miRNAs in leukemia and prostate cancer. Though he found “no earlier databases validating (his) hypothesis”, Malay adds that he found NextBio’s detailed statistics helpful:
“NextBio provides the results in Disease Atlas together with p-values, fold changes, copy number changes and z-scores. The ranking by statistical significance make the results very much practical to the researchers. It strengthens the results and makes it more justifiable.”
We were thrilled to hear that these statistics on his data supported Malay’s research!
Catarina Correia is a post-doctoral researcher in computational genomics and neurogenetics at the Instituto Gulbenkian de Ciência who works on protein networks in autism spectrum disorders. Catarina’s essay describes the importance of aggregate analysis of disease-linked gene variants to identify groups of affected pathways or biological processes. Her essay outlines how she used NextBio to identify protein sub-networks potentially important in autism and combine data from GWAS, expression profiles, CNV and mutation screenings. As she describes her analysis of public datasets:
“Information from several apps, especially Knockdown Atlas have elucidated possible mechanisms by which this gene can be implicated in autism, most of them required analysis of public datasets and are not fully described in the papers, helping us in the design of follow up studies.”
We will share the winning essays in this space over the next few weeks, so check back to hear more about these exciting research areas. We will be announcing the next round of travel grants soon, so keep an eye on this space as well!
Sorting through omics data for cancer biomarkers
Going to the AACR Annual Meeting? Visit our poster to find out more about a novel biomarker candidate for cancer!
The genome of a healthy person is constantly interacting with external signals and internal cues to adapt to a changing environment. Similarly, tumors also respond to the therapies aimed at removing them; chemotherapy and targeted molecular therapies can occasionally induce additional mutations or gene expression changes in tumor genomes. These secondary genetic changes are associated with increased drug resistance, recurrent forms of cancer and poorer chances of survival for patients.
Our presentation at the AACR Annual Meeting next week focuses on the correlations we identified for one such gene, sorting nexin 9 (SNX9). NextBio analysis of data correlations to SNX9 revealed several correlations of the gene to multiple types of cancer, including breast, prostate and other cancers. Read more…