Evidence map›Paper›PMID 30982079›Full record

ReviewCellular and molecular life sciences : CMLS2019

Computational algorithms for in silico profiling of activating mutations in cancer.

E Joseph Jordan, Keshav Patil, Krishna Suresh, Jin H Park, Yael P Mosse, Mark A Lemmon, Ravi Radhakrishnan

Open access · greenAbstract readReview
In one paragraph

Review in Cellular and molecular life sciences : CMLS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.7field-weighted citation impact, top 37% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. Trial
  2. Article
  3. Benzo[ACS omega · 2026
    Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Computational studies of anaplastic lymphoma kinase mutations reveal common mechanisms of oncogenic activation.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  9. Article
  10. Associations betweenTranslational pediatrics · 2021
    Article
  11. Machine Learning Predictions of Cancer Driver Mutations.Proceedings of the 2014 6th International Advanced Research Workshop on In Silico Oncology and Cancer Investigation : the CHIC Project Workshop (IARWISOCI) : Athens, Greece, 3-4 November 2014. International Advanced Research Workshop on... · 2014
    Article
  12. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

E Joseph JordanGraduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA, USA.
Keshav PatilDepartment of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.
Krishna SureshDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Jin H ParkDepartment of Pharmacology, Yale University, New Haven, CT, USA.
Yael P MosseDepartment of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mark A LemmonDepartment of Pharmacology, Yale University, New Haven, CT, USA.
Ravi RadhakrishnanGraduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA, USA. rradhak@seas.upenn.edu.ORCID http://orcid.org/0000-0003-0686-2851
University of Pennsylvania · USYale Cancer Center · USChildren's Hospital of Philadelphia · USUniversity City Science Center · US

Funding

PSOC@Penn Education and OutreachU54CA193417 · NCI · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2015 to 2020
$10.5M
Understanding Signaling by Non-Canonical Receptor Tyrosine KinasesR35GM122485 · NIGMS · YALE UNIVERSITY · PI Mark A Lemmon · 2017 to 2026
$7.9M
Understanding EGF receptor activation by growth factors and oncogenic mutationsR01CA198164 · NCI · YALE UNIVERSITY · PI FERGUSON, KATHRYN M, LEMMON, MARK A · 2015 to 2024
$5.2M
A plasticity and reprogramming paradigm for therapy resistance at the single cell levelU01CA227550 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RADHAKRISHNAN, RAVI, RAJ, ARJUN · 2018 to 2022
$3.3M
FP7 Ideas: European Research Council FP7-ICT-2011-9-600841NCI NIH HHS U01 CA227550NCI NIH HHS U54 CA193417NIGMS NIH HHS R35 GM122485
6 · The paper itself

Abstract

Methods to catalog and computationally assess the mutational landscape of proteins in human cancers are desirable. One approach is to adapt evolutionary or data-driven methods developed for predicting whether a single-nucleotide polymorphism (SNP) is deleterious to protein structure and function. In cases where understanding the mechanism of protein activation and regulation is desired, an alternative approach is to employ structure-based computational approaches to predict the effects of point mutations. Through a case study of mutations in kinase domains of three proteins, namely, the anaplastic lymphoma kinase (ALK) in pediatric neuroblastoma patients, serine/threonine-protein kinase B-Raf (BRAF) in melanoma patients, and erythroblastic oncogene B 2 (ErbB2 or HER2) in breast cancer patients, we compare the two approaches above. We find that the structure-based method is most appropriate for developing a binary classification of several different mutations, especially infrequently occurring ones, concerning the activation status of the given target protein. This approach is especially useful if the effects of mutations on the interactions of inhibitors with the target proteins are being sought. However, many patients will present with mutations spread across different target proteins, making structure-based models computationally demanding to implement and execute. In this situation, data-driven methods-including those based on machine learning techniques and evolutionary methods-are most appropriate for recognizing and illuminate mutational patterns. We show, however, that, in the present status of the field, the two methods have very different accuracies and confidence values, and hence, the optimal choice of their deployment is context-dependent.

Indexed as

AlgorithmsComputational BiologyComputer SimulationMutationBiomarkers, TumorHumansNeoplasmsSignal TransductionBiomarkers, TumorDriver mutationsMachine learningMolecular dynamicsPassenger mutationsStructural bioinformatics

Identifiers

PMID30982079
PMCPMC6589134
OpenAlexW2935761968

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.