genetic burden
- The number of diseases and deaths that occur as a result of inherited traits.
- The cost to the genome of mutations or selection pressure that eliminate alleles from it.
tumor mutational burden,TMB
TMB is a new clinical marker that predicts responses to immunotherapy in a range of advanced cancers.2,3,4 Unlike protein-based biomarkers, TMB is a quantitative measure of the total number of mutations per coding area of a tumor genome. Tumors that have higher levels of TMB are believed to express more neoantigens – a type of cancer-specific antigen – that may allow for a more robust immune response and therefore a more durable response to immunotherapy
prognosis
The estimate of how the disease will go for you is called prognosis
https://www.cancer.gov/about-cancer/diagnosis-staging/prognosis
http://www.cancer.ca/en/cancer-information/cancer-101/what-is-cancer/prognosis-and-survival/?region=on
MHC
http://hla.alleles.org/nomenclature/naming.html
odds ratio, OR
http://blog.sina.com.cn/s/blog_4b361fe00100y222.html
sequencing, genotyping, imputation?
Locus
A locus (plural loci) in genetics is a fixed position on a chromosome, like the position of a gene or a marker (genetic marker) .[1] Each chromosome carries many genes; human's estimated 'haploid' protein coding genes are 19,000-20,000,[2] on the 23 different chromosomes. A variant of the similar DNA sequence located at a given locus is called an allele. The ordered list of loci known for a particular genome is called a gene map. Gene mapping is the process of determining the locus for a particular biological trait.
allele
(It is now known that each of the A, B, and O alleles is actually a class of multiple alleles with different DNA sequences that produce proteins with identical properties: more than 70 alleles are known at the ABO locus.[7]
Hence an individual with "Type A" blood may be an AO heterozygote, an AA homozygote, or an AA heterozygote with two different "A" alleles.)
LOH
Loss of heterozygosity (LOH) is a cross chromosomal event that results in loss of the entire gene and the surrounding chromosomal region
中文名称：杂合性丢失英文名称：loss of heterozygosity;LOH定义：一对杂合的等位基因变成纯合状态的现象。杂合性丢失（loss of heterozygosity,LOH）：导致与一某一特殊基因正常的两个成对等位基因出 现不同的基因组变化；常反映丧失该基因的一个等位基因的部分或全部基因组序列。LOH一般都与肿瘤的抑制基因（如p53）有关，在两个等位基因都存在时， 会抑制恶性肿瘤的发生。而当一个等位基因明显异常或缺失时（另一个等位基因已经处于没有活性的状态）不再发生抑制恶性状态，细胞就转化为癌细胞。 另外一种理解：杂合性丢失（loss of heterozygosity,LOH），杂合子同源染色体上的等位基因，其中一个等位基因的部分或全部基因组序列常丢失，导致该等位基因不能表达。表现为未丧失的等位基因的纯合子性状.
http://blog.sciencenet.cn/blog-449698-520742.html
loss of heterozygosity
loss of haplotypes ?
PD1, PD-L1
PD-1全称程序性死亡受体1，英文名字为programmed death 1，是一种重要的免疫抑制分子，为CD28超家族成员。以PD-1为靶点的免疫调节在抗肿瘤、抗感染、抗自身免疫性疾病及器官移植存活等方面均有重要的意义。其配体PD-L1也可作为靶点，相应的抗体也可以起到相同的作用。
PD-L1全称程序性死亡受体-配体1，英文名字 programmed cell death-Ligand 1，是大小为40kDa的第一型跨膜蛋白。正常情形下免疫系统会对聚集在淋巴结或脾脏的外来抗原产生反应，促进具有抗原特异性的T细胞增生。而细胞程序化死亡受体-1（PD-1）与细胞程式死亡-配体1（PD-L1）结合，可以传导抑制性的信号，减低T细胞的增生。
http://news.bioon.com/article/6681978.html
Immune checkpoint
To do this, it uses “checkpoints” – molecules on certain immune cells that need to be activated (or inactivated) to start an immune response.
https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html
haplotype, 单倍型，
Allelic Imbalance
两个等位基因表达不是1:1时，就是等位基因不平等。
Humans are diploid organisms, which means we have 2 copies of each gene. Normally, these two copies are expressed at the same level. This means that the mRNA transcript from the mother and the transcript from the father will have roughly the same number of copies. Sometimes, however, this is not the case. When the ratio of the expression levels is not 1 to 1, we call it “allelic imbalance”. There are a variety of reasons why the expression may vary between the alleles. “Gene imprinting,” when environmental factors silence either the maternal or paternal allele, is one case. If one allele is silenced completely, then there will be an extreme case of allelic imbalance. Other scenarios may increase or decrease expression of one particular allele only slightly, resulting in imbalance to a lesser degree. Cis-acting mutations may alter regulation for just one allele through a change to promoter/enhancer regions (transcription factor binding sites), or even through 3′ UTR mutations that affect mRNA stability or microRNA binding.http://nathansheffield.com/wordpress/what-is-allelic-imbalance/
https://link.springer.com/protocol/10.1385%2F1-59745-377-3%3A157
b-allele frequency
In this context, the “B” allele is the non-reference allele observed in a germline heterozygous SNP, i.e. in the normal/control sample. Since the tumor cells’ DNA originally derived from normal cells’ DNA, most of these SNPs will also be present in the tumor sample. But due to allele-specific copy number alterations, loss of heterozygosity or allelic imbalance, the allelic frequency of these SNPs may be different in the tumor, and that’s evidence that one (or both) of the germline copies was gained or lost during tumor evolution.
http://cnvkit.readthedocs.io/en/stable/baf.html
Log Ratio, logR
Normalize raw data and generate log ratios. Array manufacturers generate raw intensities for each probe on an array. Many factors can influence the distribution of raw intensity values generated from each chip, and normalizing the raw values is necessary before making comparisons between subjects. The measurement that is most commonly used to determine copy number status is the “log ratio” (LR), also called “log-2 ratio” or “log-R ratio” (“R” is commonly used as a variable to represent probe intensity). The standard formula for LR calculation is log2(observed intensity/reference intensity). LR calculation requires using a reference panel to determine the “normal” or baseline intensity expected at each marker. Choosing a proper reference panel is critical as it can affect all subsequent analyses.
http://doc.goldenhelix.com/SVS/tutorials/cnv_univariate_analysis/overview.html
tumor purity
These differences, including differential gene expression, differential methylation, and different mutation and copy number variation patterns, can be used as predictors to estimate tumor purity.
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1143-5
tumor ploidy
Tumor heterogeneity
DNA samples extracted from solid tumors are rarely completely pure. Stromal or other normal cells and distinct subclonal tumor-cell populations are typically present in a sample, and can confound attempts to fit segmented log2 ratio values to absolute integer copy numbers.
CpG sites
arm focal
Teresa Davoli et al. Science 2017;355:eaaf8399
半效抑制浓度“IC50”（halfmaximal inhibitory concentration）
mutational signatures
Somatic mutations are present in all cells of the human body and occur throughout life. They are the consequence of multiple mutational processes, including the intrinsic slight infidelity of the DNA replication machinery, exogenous or endogenous mutagen exposures, enzymatic modification of DNA and defective DNA repair. Different mutational processes generate unique combinations of mutation types, termed “Mutational Signatures”.
Mutational signatures are displayed and reported based on the observed trinucleotide frequency of the human genome, i.e., representing the relative proportions of mutations generated by each signature based on the actual trinucleotide frequencies of the reference human genome version GRCh37. Note that only validated mutational signatures have been included in the curated census of mutational signatures.
http://cancer.sanger.ac.uk/cosmic/signatures
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3588146/
http://tardis.cgu.edu.tw/msignaturedb/
Signature 1
transitions versus transversions
DNA substitution mutations are of two types. Transitions are interchanges of two-ring purines (A G) or of one-ring pyrimidines (C T): they therefore involve bases of similar shape. Transversions are interchanges of purine for pyrimidine bases, which therefore involve exchange of one-ring and two-ring structures.
Although there are twice as many possible transversions, because of the molecular mechanisms by which they are generated, transition mutations are generated at higher frequency than transversions. As well, transitions are less likely to result in amino acid substitutions (due to "wobble"), and are therefore more likely to persist as "silent substitutions" in populations as single nucleotide polymorphisms (SNPs).
图片.png
mutation rate
Frequency with which a gene changes from the wild-type to a specific mutant; generally expressed as the number of mutations per biological unit (i.e., mutations per cell division, per gamete, or per round of replication).
driver and passenger mutations
The commonly accepted definition of a driver mutation is a mutation within a gene that confers a selective growth advantage (thus promoting cancer development), while passenger mutations are those that do not provide a growth advantage.
In terms of the ‘how’, there are generally two methods or approaches to classifying a mutation as a driver or passenger: 1) by frequency (driver mutations should be mutated in a greater proportion of cancer samples than would be expected from the background mutation rate) and/or 2) by prediction of functional impact (either via in-silico algorithms or cell/model-based assays). Each method is fraught with caveats and disadvantages or challenges, however the gold standard of evidence that a mutation is a driver is experimental evidence demonstrating that the mutation produces a cellular phenotype that provides a selective growth advantage to the cell. Thus, importantly, bioinformatic methods cannot provide definitive classification of mutations as either driver or passenger but can be a means by which to prioritize mutations for functional testing.
http://www.collabrx.com/driver-and-passenger-mutations-in-cancer-cell-genes/
网友评论